RESUMO
BACKGROUND: Glioblastoma multiforme (GBM), the most prevalent form of central nervous system (CNS) cancer, stands as a highly aggressive glioma deemed virtually incurable according to the World Health Organization (WHO) standards, with survival rates typically falling between 6 to 18 months. Despite concerted efforts, advancements in survival rates have been elusive. Recent cutting-edge research has unveiled bionanocatalysts with 1% Pt, demonstrating unparalleled selectivity in cleaving C-C, C-N, and C-O bonds within DNA in malignant cells. The application of these nanoparticles has yielded promising outcomes. OBJECTIVE: The objective of this study is to employ bionanocatalysts for the treatment of Glioblastoma Multiforme (GBM) in a patient, followed by the evaluation of obtained tissues through electronic microscopy. METHODS: Bionanocatalysts were synthesized using established protocols. These catalysts were then surgically implanted into the GBM tissue through stereotaxic procedures. Subsequently, tissue samples were extracted from the patient and meticulously examined using Scanning Electron Microscopy (SEM). RESULTS AND DISCUSSION: Detailed examination of biopsies via SEM unveiled a complex network of small capillaries branching from a central vessel, accompanied by a significant presence of solid carbonate formations. Remarkably, the patient subjected to this innovative approach exhibited a three-year extension in survival, highlighting the potential efficacy of bionanocatalysts in combating GBM and its metastases. CONCLUSION: Bionanocatalysts demonstrate promise as a viable treatment option for severe cases of GBM. Additionally, the identification of solid calcium carbonate formations may serve as a diagnostic marker not only for GBM but also for other CNS pathologies.
RESUMO
Bestrophin-1, a calcium-activated chloride channel (CaCC), is involved in neuropathic pain; however, it is unclear whether it has a dimorphic role in female and male neuropathic rats. This study investigated if 17ß-estradiol and estrogen receptor alpha (ERα) activation regulate bestrophin-1 activity and expression in neuropathic rats. Neuropathic pain was induced by L5-spinal nerve transection (SNT). Intrathecal administration of CaCCinh-A01 (.1-1 µg), a CaCC blocker, reversed tactile allodynia induced by SNT in female but not male rats. In contrast, T16Ainh-A01, a selective anoctamin-1 blocker, had an equal antiallodynic effect in both sexes. SNT increased bestrophin-1 protein expression in injured L5 dorsal root ganglia (DRG) in female rats but decreased bestrophin-1 protein in L5 DRG in male rats. Ovariectomy prevented the antiallodynic effect of CaCCinh-A01, but 17ß-estradiol replacement restored it. The effect of CaCCinh-A01 was prevented by intrathecal administration of MPP, a selective ERα antagonist, in rats with and without prior hormonal manipulation. In female rats with neuropathy, ovariectomy prevented the increase in bestrophin-1 and ERα protein expression, while 17ß-estradiol replacement allowed for an increase in both proteins in L5 DRG. Furthermore, ERα antagonism (with MPP) prevented the increase in bestrophin-1 and ERα protein expression. Finally, ERα activation with PPT, an ERα selective activator, induced the antiallodynic effect of CaCCinh-A01 in neuropathic male rats and prevented the reduction in bestrophin-1 protein expression in L5 DRG. In summary, data suggest ERα activation is necessary for bestrophin-1's pronociceptive action to maintain neuropathic pain in female rats. PERSPECTIVE: The mechanisms involved in neuropathic pain differ between male and female animals. Our data suggest that ERα is necessary for expression and function of bestrophin-1 in neuropathic female but not male rats. Data support the idea that a therapeutic approach to relieving neuropathic pain must be based on patient's gender.
Assuntos
Bestrofinas , Estradiol , Receptor alfa de Estrogênio , Gânglios Espinais , Neuralgia , Caracteres Sexuais , Animais , Masculino , Feminino , Neuralgia/metabolismo , Neuralgia/tratamento farmacológico , Ratos , Receptor alfa de Estrogênio/metabolismo , Estradiol/farmacologia , Estradiol/administração & dosagem , Bestrofinas/metabolismo , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Ratos Sprague-Dawley , Hiperalgesia/metabolismo , Hiperalgesia/tratamento farmacológico , Modelos Animais de Doenças , OvariectomiaRESUMO
Bestrophin-1 and anoctamin-1 are members of the calcium-activated chloride channels (CaCCs) family and are involved in inflammatory and neuropathic pain. However, their role in pain hypersensitivity induced by REM sleep deprivation (REMSD) has not been studied. This study aimed to determine if anoctamin-1 and bestrophin-1 are involved in the pain hypersensitivity induced by REMSD. We used the multiple-platform method to induce REMSD. REM sleep deprivation for 48 h induced tactile allodynia and a transient increase in corticosterone concentration at the beginning of the protocol (12 h) in female and male rats. REMSD enhanced c-Fos and α2δ-1 protein expression but did not change activating transcription factor 3 (ATF3) and KCC2 expression in dorsal root ganglia and dorsal spinal cord. Intrathecal injection of CaCCinh-A01, a non-selective bestrophin-1 blocker, and T16Ainh-A01, a specific anoctamin-1 blocker, reverted REMSD-induced tactile allodynia. However, T16Ainh-A01 had a higher antiallodynic effect in male than female rats. In addition, REMSD increased bestrophin-1 protein expression in DRG but not in DSC in male and female rats. In marked contrast, REMSD decreased anoctamin-1 protein expression in DSC but not in DRG, only in female rats. Bestrophin-1 and anoctamin-1 promote pain and maintain tactile allodynia induced by REM sleep deprivation in both male and female rats, but their expression patterns differ between the sexes.
Assuntos
Anoctamina-1 , Bestrofinas , Gânglios Espinais , Hiperalgesia , Privação do Sono , Medula Espinal , Animais , Feminino , Masculino , Ratos , Anoctamina-1/metabolismo , Bestrofinas/metabolismo , Canais de Cálcio Tipo L , Canais de Cloreto/metabolismo , Gânglios Espinais/metabolismo , Hiperalgesia/genética , Hiperalgesia/metabolismo , Ratos Wistar , Privação do Sono/metabolismo , Privação do Sono/complicações , Sono REM/fisiologia , Medula Espinal/metabolismoRESUMO
Previous studies have reported that L5/L6 spinal nerve ligation (SNL), but not L5 spinal nerve transection (SNT), enhances anoctamin-1 in injured and uninjured dorsal root ganglia (DRG) of rats suggesting some differences in function of the type of nerve injury. The role of bestrophin-1 in these conditions is unknown. The aim of this study was to investigate the role of bestrophin-1 in rats subjected to L5 SNT and L5/L6 SNL. SNT up-regulated bestrophin-1 protein expression in injured L5 and uninjured L4 DRG at day 7, whereas it enhanced GAP43 mainly in injured, but also in uninjured DRG. In contrast, SNL enhanced GAP43 at day 1 and 7, while bestrophin-1 expression increased only at day 1 after nerve injury. Accordingly, intrathecal injection of the bestrophin-1 blocker CaCCinh-A01 (1-10 µg) reverted SNT- or SNL-induced tactile allodynia in a concentration-dependent manner. Intrathecal injection of CaCCinh-A01 (10 µg) prevented SNT-induced upregulation of bestrophin-1 and GAP43 at day 7. In contrast, CaCCinh-A01 did not affect SNL-induced up-regulation of GAP43 nor bestrophin-1. Bestrophin-1 was mainly expressed in small- and medium-size neurons in naïve rats, while SNT increased bestrophin-1 immunoreactivity in CGRP+, but not in IB4+ neuronal cells in DRG. Intrathecal injection of bestrophin-1 plasmid (pCMVBest) induced tactile allodynia and increased bestrophin-1 expression in DRG and spinal cord in naïve rats. CaCCinh-A01 reversed bestrophin-1 overexpression-induced tactile allodynia and restored bestrophin-1 expression. Our data suggest that bestrophin-1 plays a relevant role in neuropathic pain induced by SNT, but not by SNL. PERSPECTIVE: SNT, but not SNL, up-regulates bestrophin-1 and GAP43 protein expression in injured L5 and uninjured L4 DRG. SNT increases bestrophin-1 immunoreactivity in CGRP+ neurons in DRG. Bestrophin-1 overexpression induces allodynia. CaCCinh-A01 reduces allodynia and restores bestrophin-1 expression. Our data suggest bestrophin-1 is differentially regulated depending on the neuropathic pain model.
Assuntos
Hiperalgesia , Neuralgia , Ratos , Animais , Bestrofinas/metabolismo , Hiperalgesia/metabolismo , Ratos Sprague-Dawley , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Neuralgia/metabolismo , Nervos Espinhais/lesões , Ligadura , Canais de Cloreto/metabolismo , Gânglios Espinais/metabolismoRESUMO
BACKGROUND: Preeclampsia origin has no conclusive explanation. As part of its etiology it has been proposed immunologic disorders. This work explores several lymphocytes subsets and postulates possible mechanisms involved in a lost of immune tolerance in this entity. OBJECTIVE: To compare cellular populations of CD3+ CD56+, CD4+ CD25+, T lymphocytes (CD4+ and CD8+) and NK cells subsets in preeclamptic and pregnant healthy women. PATIENTS AND METHODS: Through flow cytometry antibodies, peripheral blood mononuclear cells were obtained from both groups of patients. CD3+ CD56+, CD4+ CD25+, T lymphocytes (CD4+ and CD8+) and NK cells were identified. Mean and standard deviation, Student ttest and Pearson correlation were calculated to analyze differences between groups and correlation between mean blood pressure and different lymphocytes subsets; p < 0.05 was considered significant. RESULTS: CD3+ CD56+ cells percentage was lower in preeclamptic patients (2.7 vs 6.1%; p < 0.002), CD4+ CD25+ cells percentage tend to be lower too (22.11 vs 33.86; p = NS). Mean blood pressure shown negative correlation with CD3+ CD56+ cells percentage (rp - 0.666; p = 0.001) and with CD25 on CD4+ T lymphocytes surface (rp - 0.526; p < 0.025). CONCLUSIONS: Based on the association between mean blood pressure and lymphocytes percentage for these two cellular subsets, data obtained suggest that CD3+ CD56+ and CD4+ CD25+ cells play an important role in preeclampsia development.
Assuntos
Subpopulações de Linfócitos , Pré-Eclâmpsia/imunologia , Adulto , Feminino , Humanos , Contagem de Linfócitos , GravidezRESUMO
Background and Aims: The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease, we aimed to assess whether the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function. Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's disease [monozygotic n = 9, dizygotic n = 6] and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to 51Chromium [Cr]-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins. Results: Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min, both with acetylsalicylic acid [p < 0.001] and without [p < 0.001] when compared with controls. A significant increase in 51Cr-EDTA flux was already seen at 20 min in healthy monozygotic co-twins compared with controls [p≤0.05] when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins [p < 0.05] and affected twins [p < 0.05] compared with external controls, while ELISA only showed lower tricellulin in Crohn's disease twins [p < 0.05]. Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation, rather than representing a primary defect.
Assuntos
Aspirina/farmacocinética , Radioisótopos de Cromo/farmacocinética , Claudina-5/genética , Doença de Crohn , Ácido Edético/farmacocinética , Escherichia coli K12/metabolismo , Íleo , Proteína 2 com Domínio MARVEL/genética , Adulto , Quelantes/farmacologia , Doença de Crohn/genética , Doença de Crohn/patologia , Técnicas de Diagnóstico por Radioisótopos , Feminino , Predisposição Genética para Doença , Humanos , Íleo/metabolismo , Íleo/patologia , Masculino , Pessoa de Meia-Idade , Permeabilidade , Junções Íntimas/genética , Junções Íntimas/metabolismo , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genéticaRESUMO
The cervical pregnancy is a rare clinical illness among the ectopic pregnancies; the diagnosis at the moment is made by means of ultrasonography, which shows an empty uterus and a gestation in cervical channel. At the moment the preservative treatment can be made with methotrexate, without determining of precise way the factors of fault for this handling, leaving the single surgical treatment in emergency situations, avoiding the uncontrollable haemorrhage. This paper reports the case of a patient with a cervical pregnancy of nine weeks, live, with initial determination of corionic gonadotrophin hormone of 68,919 mUl/mL; reason why it is decided to interrupt the gestation being applied two doses of methotrexate; first IV of 85 mg and second with intraamniotic application. The evolution of the gestation was towards the involution and absorption of the gestational coat, the sub-unit concentrations corionic gonadotrophin hormone beta presented decrement, until undetectable, with good clinical and functional results. The gestational coat was reduced, the embryo lost beat and the gonadotrophin were in decrement until zero, with clinical evolution with stained solely haematic, without haematological and functional repercussions. Criteria of fault of the preservative treatment with methotrexate are not defined, although due the peculiarity of this illness, it is not possible to make a more extensive study, but by the reproductive benefit in young patients, it would be adapted to take it in to account like option instead of the hysterectomy.
Assuntos
Colo do Útero , Gravidez Ectópica , Adulto , Feminino , Humanos , Gravidez , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/terapiaRESUMO
Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an antiangiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure-activity relationship study to develop more potent cremastranone analogues, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis and had efficacy in the oxygen-induced retinopathy model in vivo.