RESUMO
The involvement of granulocytes in immune response against cancer is not well understood. Depending on the cytokine milieu in which they act and on their oxidative burst, granulocytes may play either an inhibitory or stimulatory role in tumour growth. Unsaturated fatty acids, essential components of cellular membranes and storage lipids, are susceptible to granulocyte-derived reactive oxygen species (ROS). ROS can induce lipid peroxidation (LPO) resulting in the destruction of biomembranes. Thus, murine W256 tumour progressing and tumour regressing animal models were used to study the involvement of plasma inflammatory mediators and oxidative burst of circulating granulocytes in malignant destruction and detrimental tumour growth. The involvement of LPO-derived aldehydes (i.e. acrolein, 4-hydroxy-2-nonenal and malondialdehyde) and myeloperoxidase (MPO) appearance in the granulocyte anti-cancer response were further evaluated. The results obtained revealed a significant increase in neutrophil elastase in animals with regressing tumour. Furthermore, the presence of MPO in tumour microenvironment was accompanied by the formation of acrolein only 5 h after tumour transplantation and its presence increased during tumour regression. Later, at an early stage of tumour regression, the presence of other LPO-derived aldehydes were also observed. The results obtained suggest that elevated neutrophil elastase and initiation of LPO may play an important role in the tumour development leading to tumour regression.
Assuntos
Acroleína/metabolismo , Granulócitos/imunologia , Granulócitos/metabolismo , Elastase de Leucócito/metabolismo , Microambiente Tumoral/imunologia , Acroleína/imunologia , Aldeídos/imunologia , Aldeídos/metabolismo , Animais , Membrana Celular/imunologia , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Progressão da Doença , Ácidos Graxos Insaturados/imunologia , Ácidos Graxos Insaturados/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Elastase de Leucócito/imunologia , Peroxidação de Lipídeos/imunologia , Peroxidação de Lipídeos/fisiologia , Masculino , Malondialdeído/imunologia , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Explosão Respiratória/imunologia , Explosão Respiratória/fisiologia , Microambiente Tumoral/fisiologiaRESUMO
Trimethyltin (TMT), an organotin compound considered a useful tool to obtain an experimental model of neurodegeneration, exhibits neurotoxicant effects selectively localised in the limbic system and especially in the hippocampus, which are different in the rat and in mice. In the rat hippocampus, we investigated the expression of aldehyde 4-hydroxynonenal, a major bioactive marker of membrane lipid peroxidation, heat shock protein (HSP) 110/105 family members, markers of oxidative stress, and the neuroinflammatory marker cyclooxygenase-2 after TMT-intoxication at various time points after treatment. Our data show that TMT-induced neurodegeneration in the rat hippocampus is associated specifically with oxidative stress and lipid peroxidation, but not with HSP expression, indicating species-specific differences in the neurotoxicity of TMT between rats and mice.
Assuntos
Aldeídos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Proteínas de Choque Térmico HSP110/metabolismo , Hipocampo , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Compostos de Trimetilestanho/toxicidade , Animais , Biomarcadores/metabolismo , Inibidores de Cisteína Proteinase/metabolismo , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Degeneração Neural/metabolismo , Ratos , Ratos WistarRESUMO
Otosclerosis is a complex disease of the human otic capsule with highest incidence in adult Caucasians. So far, many possible etiological factors like genetics, HLA, autoimmunity, viruses, inflammation, and hormones have been investigated but still the development of the disease remains unclear. Currently, the surgical replacement of stapes (stapedotomy) remains the best possible treatment option. In this review, we analyze different etiological factors studied so far in otosclerosis pathophysiology and discuss most recent findings and possible new research pathways.
Assuntos
Perda Auditiva/fisiopatologia , Otosclerose/fisiopatologia , Angiotensina II/metabolismo , Animais , Autoimunidade , Colágeno/metabolismo , Predisposição Genética para Doença , Antígenos HLA/metabolismo , Humanos , Inflamação , Vírus do Sarampo , Otosclerose/metabolismo , Estresse Oxidativo , Hormônio Paratireóideo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estribo/fisiopatologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.
Assuntos
Adenoma/metabolismo , Hormônio do Crescimento Humano/metabolismo , Neoplasias Hipofisárias/metabolismo , Tireotropina/metabolismo , Adenoma/diagnóstico por imagem , Adenoma/terapia , Adulto , Antineoplásicos Hormonais/uso terapêutico , Hormônio do Crescimento Humano/análise , Hormônio do Crescimento Humano/sangue , Humanos , Imuno-Histoquímica , Masculino , Recidiva Local de Neoplasia , Octreotida/uso terapêutico , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/terapia , Prolactina/análise , Tireotropina/sangue , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To demonstrate the clinical course in a young female with gonadotroph adenoma causing ovarian stimulation. PATIENT AND METHODS: Our patient was a 23-year-old woman with a history of oligomenorrhea who had previously undergone bilateral ovarian wedge resection owing to the clinical appearance of polycystic ovaries. Two years later, she sought treatment for headache, galactorrhea, history of spotting and lower abdominal distension. FSH, LH, beta-LH, inhibin A and B, estradiol, prolactin (PRL), and beta-chorionic gonadotrophin (beta-CG) were measured, and the responses of FSH, LH and beta-LH to thyrotrophin-releasing hormone (TRH) were documented. Immunohistochemical analysis of the tumor tissue was performed after surgery. Five years after the trans-sphenoidal surgery, the patient again became oligomenorrheic. A large recurrent adenoma was diagnosed on CT one year later. Transvaginal ultrasound showed ovaries of normal size with multiple small cystic formations simulating a polycystic pattern, While the patient was awaiting surgery, a pituitary apoplexy occurred. Emergency decompressive surgery was performed and the patient fully recovered. RESULTS: Enlarged ovaries were found on ultrasound examination simulating a hyperstimulation-like pattern. At that time, elevated levels of FSH (13.4IU/l) and marginally elevated levels of beta-LH (1.43ng/ml) were found, whereas the level of LH (0.5IU/l) was subnormal. Plasma estradiol was markedly supranormal (6150pmol/l). Levels of inhibin A and B were elevated (326pg/ml and 588pg/ml respectively). The prolactin level (70ng/ml) was increased, whereas beta-chorionic gonadotrophin (beta-CG) was normal. Significantly increased FSH, LH, and beta-LH responses to TRH stimulation were documented. Pituitary macroadenoma was found on MRI scan and removed by trans-sphenoidal surgery. Immunohistochemical examination showed high positivity for beta-CG and LH, and slight positivity for FSH. Five years after the surgery, estradiol was elevated (1160pmol/l), whereas basal levels of LH (4.65IU/l) and FSH (3.98IU/l) were not suppressed. After the second operation, immunostaining of the adenoma tissue confirmed the previous findings. CONCLUSIONS: Measurement of gonadotrophins in our case did not prove to be a method for identifying a large recurrent gonadotroph pituitary adenoma. The sonographic ovarian imaging varied from a polycystic- to an ovarian hyperstimulation-like pattern during the evolution of the tumour.
Assuntos
Adenoma/fisiopatologia , Gonadotropinas/metabolismo , Síndrome de Hiperestimulação Ovariana/fisiopatologia , Neoplasias Ovarianas/fisiopatologia , Adenoma/complicações , Adenoma/metabolismo , Adulto , Células Cultivadas , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Imageamento por Ressonância Magnética , Microscopia Eletrônica , Síndrome de Hiperestimulação Ovariana/diagnóstico por imagem , Síndrome de Hiperestimulação Ovariana/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/metabolismo , Recidiva , UltrassonografiaRESUMO
Immunohistochemical analysis of the distribution of the lipid peroxidation product 4-hydroxynonenal (HNE) in the brain of baboons exposed to experimental hemorrhagic traumatic shock or sepsis showed that systemic oxidative stress and the thereby generated HNE affect the blood:brain barrier and the regulation of cerebral blood flow determining secondary brain damage. Similarly, HNE was determined during ischemia in the brain blood vessels of rats exposed to ischemia/reperfusion injury of the brain. After reperfusion, HNE disappeared from the blood vessels but remained in neurones and in glial cells. Since HNE modulates cell proliferation and differentiation (including proto-oncogene expression), it is postulated that HNE might have prominent local and systemic effects that are not only harmful but beneficial, too, determining the outcome of various pathophysiological conditions based on oxidative stress.
Assuntos
Aldeídos/metabolismo , Sistemas do Segundo Mensageiro/fisiologia , Aldeídos/imunologia , Aldeídos/farmacologia , Animais , Anticorpos Monoclonais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Divisão Celular/efeitos dos fármacos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/metabolismo , Radicais Livres/metabolismo , Células HeLa , Humanos , Imuno-Histoquímica , Ataque Isquêmico Transitório/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Papio , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Sistemas do Segundo Mensageiro/imunologia , Sepse/metabolismo , Choque/complicações , Choque/metabolismo , Timidina/metabolismoRESUMO
BACKGROUND: Previous studies have shown that the lipid peroxidation product 4-hydroxynonenal (HNE) acts as a cell growth modulator if used at low, physiological concentrations being strongly cytotoxic at higher concentrations for a number of cells. These effects of HNE also appeared to be mutually dependent on the effects of serum growth factors. The aim of this investigation was to study the concentration-dependent response of human cervical carcinoma (HeLa) cells in vitro with respect to the intracellular uptake of exogenous HNE, the cellular energy metabolism, DNA synthesis, overall gene expression and susceptibility to apoptosis. MATERIALS AND METHODS: MTT assay was applied as an index of energy metabolism and the replicative activity was quantitated by the 3H-thymidine incorporation assay. The occurence and intracellular distribution was studied with monoclonal antibodies directed against HNE-protein conjugates. Binding of HNE to serum proteins was determined with the same antibodies by Western blotting. Differential gene expression was studied by differential display RT-PCR while a novel photometric assay, denoted Titer-TACS, was used for in situ detection and quantitation of apoptosis in monolayer cell cultures. RESULTS: A physiological concentration of HNE (1 microM) had hardly any effect on the parameters of the replicative activity and the energy metabolism. No morphological changes were observed and the number of HNE-positive cells was not significantly different when compared to the untreated control cells, while most of the aldehyde appeared to be bound to serum proteins (albumin fraction). A ten-fold higher concentration (10 microM) was found to be cytostatic. Spindle-shaped cells with a picnotic nucleus were observed occasionally, as well as membrane blebs, which were HNE-positive. The number of HNE-positive cells was significantly increased compared both to the control cells and cells treated with 1 microM HNE, but in the presence of serum the effects of 10 microM HNE were negated due to its binding to the serum proteins. Finally, 100 microM HNE was cytotoxic for the HeLa cells. Most of the cells were picnotic, together with a few spindle-shaped or oval cells. The staining for HNE was diffuse and strong (90% of the cells were HNE-positive) while even binding of the aldehyde to serum proteins did not prevent its cytotoxic effects. This concentration of HNE caused acute stress response of the cells resulting in the decreased expression of several as yet unidentified genes. The altered pattern of gene expression was followed by programmed cell death, i.e. an increased number of apoptotic cells after treatment with low (1 and 10 microM) concentrations of HNE. A rebound effect was observed, i.e. a decrease of apoptotic cells after 24 hours followed by an overshooting increase after 48 hours. CONCLUSIONS: For HeLa carcinoma cells there appears to be a concentration range of HNE where it does not cause necrosis but preferentially apoptosis. At this concentration range HNE is cytochemically detectable within the cells as a protein conjugate. It is proposed that a possible differential sensitivity of cancer cells and their normal counterparts to the cytostatic activity of HNE should be explored.
Assuntos
Aldeídos , Apoptose , Carcinógenos , Western Blotting , Carcinoma/metabolismo , Carcinoma/patologia , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Cisteína Proteinase , Relação Dose-Resposta a Droga , Feminino , Células HeLa , Humanos , Imuno-Histoquímica , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sais de Tetrazólio/farmacologia , Tiazóis/farmacologia , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
Advanced glycation endproducts (AGE) accumulate over proteins as a consequence of diabetic hyperglycemia, and thus contribute to the pathogenesis of diabetic complications. To improve the understanding of the pathology of diabetic neuropathy, AGE accumulation was analyzed in sural and/or femoral nerves obtained under spinal anesthesia from 8 type 2 diabetic patients with both distal symmetrical polyneuropathy and proximal neuropathy. Pronounced AGE immunoreactivity was detected on axons and myelin sheaths in 90% of diabetic peripheral nerves but not in the control specimen. The intensity of axonal AGE immunopositivity significantly correlated with the severity of morphological alterations (p<0.005). AGE localization, demonstrated by immunohistochemical methods, was also present in the endoneurium, perineurium and microvessels. Morphometric analysis of the diabetic peripheral nerve showed perineurial thickening (diabetic vs. control, 15.5+/-4.9 vs. 6.6+/-2.1 microm, p<0.001), narrowing of the microvessel lumina (66.6+/-50.5 vs. 579.5+/-38.4 x10(3) microm(2), p<0.001) and significant reduction in the number of preserved axons (3.6+/-3 vs. 8.9+/-2.3 per 10(5) microm(2) per area, p<0.037). The sera of diabetic patients contained epitope(s) of AGE structure and soluble immune complexes containing AGE moiety. In conclusion, to the best of our knowledge, this is the first study providing evidence for excessive AGE formation on peripheral nerve components, primarily axons, and a significantly higher level of circulating AGE-immune complexes in patients with both distal diabetic polyneuropathy and proximal neuropathy. Humoral immune mechanisms, including the production of anti-AGE autoantibody, may potentially be involved in the development of structural abnormalities described in this report.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Neuropatias Diabéticas/metabolismo , Nervo Femoral/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Nervo Sural/metabolismo , Idoso , Complexo Antígeno-Anticorpo/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/imunologia , Neuropatias Diabéticas/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Nervo Femoral/patologia , Imunofluorescência , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Sural/patologiaRESUMO
We described before that iron-containing, anti-anaemic drug, ferric-sorbitol-citrate complex (FSC) inhibited proliferation of various murine cancer cells in vitro and caused tumour regression in vivo, but did not affect proliferation of the non-malignant cells. The aim of this study was to evaluate further the anticancer activity mechanism of FSC using human colon cancer cell line CaCo2. After treatment with FSC for 72 hours impaired proliferative ability and viability of CaCo2 cells as observed. Growth modification caused by FSC involved diminished expression of Bcl-2, and over-expression of mp53 proto-oncogenes, accompanied by increased incidence of apoptosis. Immunostaining the cells applying monoclonal antibodies for lipid peroxidation product 4-hydroxynonenal (HNE) showed that FSC-iron increased intracellular HNE, but did not induce severe HNE-mediated oxidative stress. Thus, antitumorous mechanism of FSC involves modulation of oncogene expression and induction of apoptosis apparently not triggered by lipid peroxidation-mediated oxidative stress, although FSC might restore endogenous HNE production in the CaCo2 cells to level resembling physiological for various non-malignant cells and tissues. Higher dose of FSC increased also number of intracellular ferritin positive CaCo2 cells.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ácido Cítrico/farmacologia , Compostos Férricos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Proto-Oncogenes , Sorbitol/farmacologia , Aldeídos/metabolismo , Células CACO-2 , Combinação de Medicamentos , Genes p53 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/fisiologiaRESUMO
The activity principle of the mistletoe (Viscum album L.) phytotherapeutics could be considered as combined cytotoxic and "biological response modifying" activities (increasing host defense against cancer) that result from the activities of the plant lectins and the other biologically relevant substances. We found before that the aqueous extract Isorel, produced by Novipharm GmbH (Pörtschach, Austria) from the entire plant (planta tota) of fresh mistletoe under standardized conditions with bioassay validated batch consistency, can be valuable in experimental adjuvant cancer therapy increasing efficiency of cyclophosphamide chemotherapy. In current study we found that Isorel increases the reactivity of the tumor-bearing mice lymphocytes to the mitogens (ConA and LPS) in vitro, thus indicating its immune stimulating effects for the cancer-immunosuppressed lymphocytes. Moreover, Isorel inhibited the incorporation of 3H-labelled amino acids (protein synthesis) in various malignant cell lines. For the growth inhibition mostly higher MW components were responsible, although even less than 500 Da components were also active. We further analyzed the effects of drug application in vicinity of tumor (murine mammary carcinoma) and compared it with systemic effects. The animals carried mammary carcinoma in both hind limbs and were also injected with tumor cells i.v. to develop artificial lung metastases. Isorel was applied only at the right side (in the limb distal from the tumor) and caused persistent and almost complete inhibition of the tumor growth for 2/7 animals. Anticancer effects were less pronounced on the contralateral side tumors, although tumor growth rate was transiently reduced for some mice. Histology revealed that Isorel treatment, both at the side of tumor and systemically, increased the incidence of apoptosis and necrosis in the tumors, while reduction of mitosis was noticed only for the tumors in vicinity of the tumor exposed to Isorel. Finally, animals treated with Isorel had, on the average, three times less lung metastases than the controls. Thus, we conclude that both local and systemic effects of the application of Isorel could be of benefit for the tumor-bearing organism resulting in immunomodulation combined with tumor growth inhibition and reduction of metastases. According to the in vitro results, antitumorous effects could be the result not only of the mistletoe lectins and the other high MW factors, but also of the very low MW (< 500 Da) substances that deserve further analyses.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Melanoma Experimental/imunologia , Fitoterapia , Extratos Vegetais/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Concanavalina A/farmacologia , Sinergismo Farmacológico , Feminino , Lipopolissacarídeos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/secundário , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Extratos Vegetais/farmacologia , Lectinas de Plantas , Plantas Medicinais/química , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
There are numerous attempts to find novel anticancer drugs or to improve therapeutic protocols based on application of chemotherapeutic agents and immunomodulators (biological response modifiers, cytokines, various plant or bacterial products). Among the preparations that have beneficial effects for the cancer bearing organism are preparations of spleen peptides (Polyerga). Hence, we analyzed if treatment with spleen oligopeptides GP-1 (active substance for the manufacture of Polyerga ampoules' solution injected as 0.5 microgram/kg every second day) if given alone or combined with chemotherapy (Endoxan 50 mg/kg single i.p. dose) of mice bearing artificial lung metastases of mammary carcinoma will have an impact on the metastases count and survival of the animals. The results obtained have shown that chemotherapy reduced metastases count and increased survival of the tumor bearing mice, while the use of GP-1 alone did not affect metastases development. However, combined GP-1 treatment and chemotherapy were more efficient in prevention of the metastases development than chemotherapy alone. Thus, in mice treated with GP-1 and Endoxan, the average metastases count was four times lower than in the mice treated by chemotherapy only, while 2/12 animals were without tumor nodules in the lungs. Finally, all the animals treated by chemotherapy alone died until the 42nd day after tumor transplantation, while at the same time, only 5/10 animals died receiving combined therapy. Thus, these results give an experimental support for the use of the spleen peptides in biotherapy (or combined therapy) of cancer.
Assuntos
Antineoplásicos/uso terapêutico , Glicopeptídeos/uso terapêutico , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/tratamento farmacológico , Fenóis/uso terapêutico , Animais , Ciclofosfamida/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Neoplasias Pulmonares/prevenção & controle , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos CBA , Baço , SuínosRESUMO
The aim of the study was to determine whether changes in serum levels of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1) are related to the phenomenon of enhanced osteogenesis in patients with bone fracture combined with traumatic brain injury (TBI), which would also suggest their involvement in post-traumatic stress and their applicability in the promotion of bone fracture healing. GH values were increased during the initial post-traumatic period in all patients (those with bone fractures or TBI alone or combined injury associated with enhanced osteogenesis), declining to normal values afterwards. However, a further increase in GH was only observed in patients with combined injury overlapping with the time of clinically manifested enhanced osteogenesis. Serum levels of IGF-1 were above normal throughout the study period (14 weeks) in patients with TBI only, but not if TBI was combined with bone fractures followed by enhanced osteogenesis. In these patients IGF-1 values increased gradually during fracture healing, as was also the case in patients with bone fractures alone. Thus, different patterns of post-traumatic changes in both GH and IGF-1 were seen in patients with TBI or bone fractures in comparison to those with combined injury, indicating the involvement of these substances in the post-traumatic stress response and in the phenomenon of enhanced osteogenesis in patients with bone fractures and TBI.
Assuntos
Lesões Encefálicas/sangue , Fraturas Ósseas/sangue , Hormônio do Crescimento Humano/sangue , Acidentes de Trânsito , Adolescente , Adulto , Lesões Encefálicas/complicações , Interpretação Estatística de Dados , Feminino , Consolidação da Fratura , Fraturas Ósseas/complicações , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Ossificação Heterotópica/etiologia , Osteogênese , Fatores de TempoRESUMO
Phenomenon of spontaneous regression of cancer indicates that recovery from malignant disease can happen without the application of any so far known therapeutic treatment. The most of the self-cured patients have undergone surgical operation which did not eliminate entire tumor or did not affect malignant tissue at all. Furthermore, regression or reversion of tumors (transformation of tumor cells into normal, nonmalignant cells) can be achieved in plants or amphibia after exposure of tumor cells to the influence of normal, regenerating tissue. Thus, it seems that during tissue regeneration certain local changes in tissue happen (synthesis of some regulatory growth factors) which induce dying of tumor cells or modify main features of malignant cells. Previously we have studied growth of murine malignant tumors in regenerating tissue of liver and skin. Obtained results indicated that under the influence of regenerating tissue anaplasia of fibrosarcoma decreases, as well as do pigmentation and the incidence of live cells in melanoma B16 tissue. Thus, it is obvious that mechanism of regenerating tissue growth control, which can also change characteristics of tumor cells, exists in mammalia, too. In order to analyse whether the same homeostatic mechanism is responsible for the phenomenon of spontaneous regression of human cancer, we have analysed the growth of melanoma B16 in back limb of nonoperated and sham or partially hepatectomized mice. Regeneration of skin and abdominal wall tissue in sham hepatectomized animals slowed down tumor growth, while liver regeneration completely inhibited tumor progression. Tumor growth inhibition was result of tumor tissue necrosis which developed around blood vessels. However, the structure and integrity of blood vessels themselves was normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Regeneração Hepática/fisiologia , Melanoma Experimental/patologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transplante de NeoplasiasRESUMO
In the group of 13 patients with Cushing's syndrome (CS) CRH test was performed by sampling the blood from peripheral vein and in eight patients also after inferior petrosal sinus catheterization (IPSC) to resolve the disease etiology. In the group of patients with Cushing's disease (CD, n = 11), which was proven by surgery and adenoma immunohistochemistry, 10/11 had in CRH test the significant increase of cortisol and ACTH in the peripheral blood. Among two patients with ectopic ACTH syndrome one had the significant increase of both hormones in CRH test. After IPSC the ratio of ACTH in the petrosal sinus and in the peripheral vein was significant in 4/8 patients before, and in 6/8 after CRH administration. The intersinus gradient was significant in 3/8 patients before, and in 4/8 after CRH test. According to our results we can conclude that the determination of ACTH in the blood from peripheral veins after CRH administration is a very sensitive method for differential diagnosis of CS, while the results after IPSC were less sensitive in our conditions than those described in the literature.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Hormônio Liberador da Corticotropina , Síndrome de Cushing/diagnóstico , Hidrocortisona/sangue , Síndrome de ACTH Ectópico/complicações , Síndrome de ACTH Ectópico/diagnóstico , Adolescente , Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/diagnóstico , Adenoma Adrenocortical/complicações , Adenoma Adrenocortical/diagnóstico , Adulto , Síndrome de Cushing/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amostragem do Seio Petroso , Sensibilidade e EspecificidadeRESUMO
This study deals with the topographic distribution of traumatic lesions in the corpus callosum within the pattern of "inner cerebral trauma". Material for neuropathological investigations consisted of 49 brains of patients who suffered closed head injury of the acceleration type with linear translation of acceleration acting along the longer axis of the head. As a control, 5 brains were investigated in which the direction of linear translation was latero-lateral. The patients were divided into 4 groups according to reconstruction of the traumatic event and ascertaining of the direction of the linear translation of acceleration: (1) Medial blow (antero-posterior and postero-anterior), (2) Semioblique left blow (frontal left-occipital right and occipital right-frontal left), (3) Semioblique right blow (frontal right-occipital left and occipital left-frontal right), (4) Vertex-base direction. Fornix and septum pellucidum, as anatomically adjacent structures were also investigated. The results showed that the lesions in the corpus callosum were related to the pattern of "inner cerebral trauma" (ICT) (Grcevic 1982), and the biomechanical conditions originally proposed by Lindenberg. These investigations, carried out on a representative material of 54 brains and by subserial histological analysis of the entire corpus callosum, produced a new evidence for our previous preliminary observations about the correlation of the shape and distribution of the periaxial lesions of the pattern of "inner cerebral trauma" and direction of the linear translation of accelerating forces. Our present investigations showed a striking congruence between the pattern of lesions within the corpus callosum in such type of cerebral trauma and the course of linear translation of acceleration. Furthermore, this study proved the importance of topographic interpretation of lesions in the corpus callosum in vivo i.e. by the CT and MRI examinations, because they may serve as a significant information for reconstruction of the biomechanical conditions of the injury which can be of importance for early therapeutical strategy and forensic interpretations of the accident. By using silver impregnation-techniques for histopathological study of the corpus callosum, we could confirm our previously expressed concept on "focalized" and not "diffuse" axonal injures in ICT (Grcevic 1988). In this study corpus callosum served as a representative anatomical structure for axonal studies showing that axonal lesions strictly follow the pattern of tissue lesions with definite focal principle.
Assuntos
Corpo Caloso/lesões , Traumatismos Cranianos Fechados/patologia , Aceleração , Adolescente , Adulto , Idoso , Criança , Corpo Caloso/patologia , Feminino , Traumatismos Cranianos Fechados/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A case of endotheliomatous type of meningioma arising from the falx and dura of the left anterior cranial fossa is reported. Numerous Rosenthal fibres were observed in the gliotic tissue around the meningioma. Authors present a brief data about the nature and occurrence of Rosenthal fibres. The occurrence of the pilocytic astrocytes and Rosenthal fibres in the gliotic tissue around slow-growing falx meningioma is an additional evidence for a peculiar type of changes in astrocytes of the long-standing gliosis of piloid type.
Assuntos
Encéfalo/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Feminino , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Pessoa de Meia-Idade , RadiografiaRESUMO
From the group of patients with clinically manifested closed head injuries, patients with minimal traumatic lesions in the brain parenchyma, were separated and in addition radiographically analyzed. There were 22 patients in the group. On plain CT scans they had foci 5 to 10 mm large caused by trauma. CT is suitable investigation technique for detecting minimal traumatic brain lesions. Besides, CT is suitable for the follow up of the lesion evolution dynamics, which comprises not only changes in the lesions density but also the possibility of registering primarily reversible but macroscopically (invisible) lesions into (visible) reversible lesions on the control scans. The finding of only one or two minimal lesions in critical locations in the "inner cerebral trauma" always indicated the existence of possible lesions in other locations within the known pattern of the ICT. Minimal traumatic lesions of the brain frequently occur in ICT or in all cases where the acceleration of traumatizing forces has anteroposterior or postero-anterior course of direction. Their recognition by neuroimaging methods is of great importance due to the central localization of the foci, which otherwise cannot be detected by other methods.
Assuntos
Lesões Encefálicas/diagnóstico por imagem , Traumatismos Cranianos Fechados/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report two siblings of Croatian consanguineous healthy parents with a novel homozygous missense mutation in the POMT1 gene, presenting with intellectual disability and psychotic, in particular hallucinatory symptoms and abnormal brain MRIs, preceding classical symptoms of limb-girdle muscular dystrophy by several years. Weakness became apparent in early adulthood and both siblings remained ambulant into the 3rd and 4th decade of life. The muscle biopsy showed reduced α-dystroglycan compatible with the POMT1 defect. This case report extends the phenotypic spectrum of POMT1 associated muscular dystrophies to the adult onset limb girdle muscular dystrophies with psycho-organic deficits.
Assuntos
Transtornos Cognitivos/etiologia , Manosiltransferases/genética , Transtornos Mentais/etiologia , Distrofia Muscular do Cíngulo dos Membros/complicações , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação/genética , Adulto , Encéfalo/patologia , Transtornos Cognitivos/genética , Consanguinidade , Análise Mutacional de DNA , Feminino , Humanos , Imageamento por Ressonância Magnética , Transtornos Mentais/genética , IrmãosRESUMO
We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 microg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (microg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.