RESUMO
Cadmium (Cd) is a transition heavy metal that is able to accumulate in the central nervous system and may induce cell death through reactive oxygen species (ROS)-mediated mechanisms and inactivating the antioxidant processes, becoming an important risk factor for neurodegenerative diseases. The antioxidant effects of cannabinoid receptor modulation have been extensively described, and, in particular, ß-Caryophyllene (BCP), a plant-derived cannabinoid 2 receptor (CB2R) agonist, not only showed significant antioxidant properties but also anti-inflammatory, analgesic, and neuroprotective effects. Therefore, the aim of the present study was to evaluate BCP effects in a model of Cd-induced toxicity in the neuroblastoma SH-SY5Y cell line used to reproduce Cd intoxication in humans. SH-SY5Y cells were pre-treated with BCP (25, 50, and 100 µM) for 24 h. The day after, cells were challenged with cadmium chloride (CdCl2; 10 µM) for 24 h to induce neuronal toxicity. CdCl2 increased ROS accumulation, and BCP treatment significantly reduced ROS production at concentrations of 50 and 100 µM. In addition, CdCl2 significantly decreased the protein level of nuclear factor erythroid 2-related factor 2 (Nrf2) compared to unstimulated cells; the treatment with BCP at a concentration of 50 µM markedly increased Nrf2 expression, thus confirming the BCP anti-oxidant effect. Moreover, BCP treatment preserved cells from death, regulated the apoptosis pathway, and showed a significant anti-inflammatory effect, thus reducing the pro-inflammatory cytokines increased by the CdCl2 challenge. The results indicated that BCP preserved neuronal damage induced by Cd and might represent a future candidate for protection in neurotoxic conditions.
Assuntos
Neuroblastoma , Sesquiterpenos , Humanos , Cádmio/toxicidade , Sesquiterpenos/farmacologia , Receptor CB2 de Canabinoide , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Anti-Inflamatórios não Esteroides , Linhagem Celular TumoralRESUMO
Many natural substances commonly found in healthy diets have been studied for their potential to reduce male infertility associated with varicocele. A positive role of selenium (Se) or lycopene alone was demonstrated in experimental varicocele, while no data are available on their association. One group of male Sprague-Dawley rats was sham operated and daily treated with Se (3 mg/kg, i.p.), lycopene (1 mg/kg, i.p.), or their association. A second group underwent surgery to induce varicocele. Sham and half of the varicocele animals were sacrificed after twenty-eight days, while the residual animals were treated for one more month and then sacrificed. In varicocele animals, testosterone levels and testes weight were reduced, Hypoxia Inducible Factor-1α (HIF-1α) expression was absent in the tubules and increased in Leydig cells, caspare-3 was increased, seminiferous epithelium showed evident structural changes, and many apoptotic germ cells were demonstrated with TUNEL assay. The treatment with lycopene or Se alone significantly increased testis weight and testosterone levels, reduced apoptosis and caspase-3 expression, improved the tubular organization, decreased HIF-1α positivity of Leydig cells, and restored its tubular positivity. Lycopene or Se association showed a better influence on all biochemical and morphological parameters. Therefore, the nutraceutical association of lycopene plus Se might be considered a possible therapeutic tool, together with surgery, in the treatment of male infertility. However, long-term experimental and clinical studies are necessary to evaluate sperm quantity and quality.
Assuntos
Infertilidade Masculina , Selênio , Varicocele , Masculino , Ratos , Animais , Humanos , Ratos Sprague-Dawley , Selênio/farmacologia , Licopeno/farmacologia , Varicocele/tratamento farmacológico , Sêmen , Suplementos Nutricionais , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/etiologia , TestosteronaRESUMO
Varicocele is one of the main causes of infertility in men, thus representing an important clinical problem worldwide. Inflammation contributes mainly to its pathogenesis, even if the exact pathophysiological mechanisms that correlate varicocele and infertility are still unknown. In addition, oxidative stress, apoptosis, hypoxia, and scrotal hyperthermia seem to play important roles. So far, the treatment of varicocele and the care of the fertility-associated problems still represent an area of interest for researchers, although many advances have occurred over the past few years. Recent experimental animal studies, as well as the current epidemiological evidence in humans, demonstrated that many functional foods of natural origin and nutraceuticals that are particularly abundant in the Mediterranean diet showed anti-inflammatory effects in varicocele. The aim of the present narrative review is to mainly evaluate recent experimental animal studies regarding the molecular mechanisms of varicocele and the state of the art about possible therapeutic approaches. As the current literature demonstrates convincing associations between diet, food components and fertility, the rational intake of nutraceuticals, which are particularly abundant in foods typical of plant-based eating patterns, may be a reliable therapeutic supportive care against varicocele and, consequently, could be very useful in the cure of fertility-associated problems in patients.
Assuntos
Infertilidade Masculina , Varicocele , Masculino , Animais , Humanos , Varicocele/complicações , Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Alimento Funcional , Modelos Animais , Suplementos NutricionaisRESUMO
Polydeoxyribonucleotide (PDRN) is an agonist of the A2A adenosine receptor derived from salmon trout sperm. Selenium (Se) is a trace element normally present in the diet. We aimed to investigate the long-term role of PDRN and Se, alone or in association, after ischemia-reperfusion (I/R) in rats. The animals underwent 1 h testicular ischemia followed by 30 days of reperfusion or a sham I/R and were treated with PDRN or Se alone or in association for 30 days. I/R significantly increased hypoxia-inducible factor 1-α (HIF-1α) in Leydig cells, malondialdehyde (MDA), phosphorylated extracellular signal-regulated kinases 1/2 (pErk 1/2), and apoptosis decreased testis weight, glutathione (GSH), testosterone, nuclear factor erythroid 2-related factor 2 (Nrf2), induced testicular structural changes, and eliminated HIF-1α spermatozoa positivity. The treatment with either PDRN or Se significantly decreased MDA, apoptosis, and HIF-1α positivity of Leydig cells, increased testis weight, GSH, testosterone, and Nrf2, and improved the structural organization of the testes. PDRN and Se association showed a higher protective effect on all biochemical, structural, and immunohistochemical parameters. Our data suggest that HIF-1α could play important roles in late testis I/R and that this transcriptional factor could be modulated by PDRN and Se association, which, together with surgery, could be considered a tool to improve varicocele-induced damages.
Assuntos
Traumatismo por Reperfusão , Selênio , Ratos , Masculino , Animais , Polidesoxirribonucleotídeos/farmacologia , Fator 2 Relacionado a NF-E2/análise , Selênio/farmacologia , Selênio/análise , Ratos Sprague-Dawley , Sêmen , Testículo , Isquemia , Traumatismo por Reperfusão/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Reperfusão , Testosterona/análiseRESUMO
Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1ß and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1ß expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.
Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polidesoxirribonucleotídeos/administração & dosagem , Selenometionina/administração & dosagem , Varicocele/tratamento farmacológico , Animais , Caspase 1/genética , Modelos Animais de Doenças , Quimioterapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Polidesoxirribonucleotídeos/farmacologia , Ratos , Selenometionina/farmacologia , Testosterona/metabolismo , Varicocele/genética , Varicocele/metabolismoRESUMO
The greatest challenge of modern implantology is the loss of bone tissue in esthetic region of maxilla and mandible. Significant bone changes caused for example by cysts, unerupted teeth or traumatic extraction often provoke bilateral or trilateral bone defects. Thanks to the possibility of applying demineralized dentin and dentin blocks gained from extracted teeth of the patient, it is possible to successfully regenerate bone tissue especially in the esthetic zone. AIM: The aim of the study was to present a case of a patient who underwent bone augmentation for implantation. In addition, a review of the literature illustrating the effectiveness of autogenous bone graft material derived from ground teeth in augmentation procedures was performed. A CASE REPORT: The paper presents a case of a 26-year-old man in whom bone defect was augmented with material derived from dentin blocks and partially demineralized dentin processed in the BonMaker device after extraction of the root of tooth 11. A systematic review of literature was conducted analyzing articles published between 1975 and 2020. From 80 articles, 25 were selected for this study. CONCLUSIONS: The presented case and the systematic review of literature indicate that tooth-derived bone graft material prepared from extraction can effectively restore alveolar bone defect. The results we get so far are very satisfying. Further studies should be performed to confirm the osteogenic effects and safety use of this tooth based graft material.
Assuntos
Regeneração Óssea , Dentina , Adulto , Humanos , Masculino , Mandíbula , Extração Dentária/efeitos adversosRESUMO
The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal ß2-adrenergic receptor (ß2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal ß2-AR antibody. The results show that immunoreactivity for ß2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for ß2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates ß2-AR expression in the human cortex and provides suggestions on the possible involvement of ß2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death.
Assuntos
Glândulas Suprarrenais/metabolismo , Expressão Gênica , Receptores Adrenérgicos beta 2/metabolismo , Adolescente , Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptores Adrenérgicos beta 2/genética , Adulto JovemRESUMO
INTRODUCTION: Placental site trophoblastic tumor (PSTT) is a form of gestational trophoblastic disease that originates from the implantation of an intermediate trophoblast. It was described for the first time by Von F. Marchand in 1895 as belonging to chorioepithelioma sui generis, a pathological condition with many variations and a progressive degree of malignancy. METHODS: We have conducted a literature review in MEDLINE about epidemiology, etiopathogenesis and clinical features of PSTT. Moreover, a case that occurred in our institution was reported. RESULTS: Our research has highlighted that existing published data about PSTT are not uniform. The number of cases described in the literature has updated and the clinical features of selected "case series" of patients diagnosed with PSTT were showed. The etiopathogenesis was discussed. It was noted that current prognostic factors still allow important information regarding PSTT to be obtained, albeit fragmentary. CONCLUSIONS: The lack of uniformity in data collection seen so far has limited full knowledge of PSTT. For this reason, we suggest a model (PSTT model) that collects and unifies PSTT evidence as this would be useful to identify worldwide precise prognostic factors, which are still lacking. When PSTT is diagnosed, the proper procedure seems to be total hysterectomy, with sampling of pelvic lymph nodes and ovarian conservation. For advanced-stage diseases, (stage III and IV) a combination of surgery and polychemotherapy is suggested.
Assuntos
Histerectomia/métodos , Tumor Trofoblástico de Localização Placentária/epidemiologia , Neoplasias Uterinas/epidemiologia , Coriocarcinoma/epidemiologia , Feminino , Humanos , Gravidez , Neoplasias Uterinas/cirurgiaRESUMO
Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated that Serenoa repens (Ser) with lycopene (Ly) and selenium (Se) reawakened apoptosis by reducing survivin and neuronal apoptosis inhibitory protein (NAIP) levels in rats. The aim of this study was to evaluate the effectiveness of Ser-Se-Ly association on survivin and NAIP expression in BPH patients. Ninety patients with lower urinary tract symptoms (LUTS) due to clinical BPH were included in this randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive placebo (Group BPH + placebo, n = 45) or Ser-Se-Ly association (Group BPH + Ser-Se-Ly; n = 45) for 3 months. At time 0, all patients underwent prostatic biopsies. After 3 months of treatment, they underwent prostatic re-biopsy and specimens were collected for molecular, morphological, and immunohistochemical analysis. After 3 months, survivin and NAIP were significantly decreased, while caspase-3 was significantly increased in BPH patients treated with Ser-Se-Ly when compared with the other group. In BPH patients treated with Ser-Se-Ly for 3 months, the glandular epithelium was formed by a single layer of cuboidal cells. PSA showed high immunoexpression in all BPH patients and a focal positivity in Ser-Se-Ly treated patients after 3 months. Evident prostate specific membrane antigen (PSMA) immunoexpression was shown in all BPH patients, while no positivity was present after Ser-Se-Ly administration. Ser-Se-Ly proved to be effective in promoting apoptosis in BPH patients.
Assuntos
Proteínas Inibidoras de Apoptose/metabolismo , Proteína Inibidora de Apoptose Neuronal/metabolismo , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Idoso , Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores , Carotenoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glutamato Carboxipeptidase II/genética , Glutamato Carboxipeptidase II/metabolismo , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose/genética , Licopeno , Masculino , Pessoa de Meia-Idade , Proteína Inibidora de Apoptose Neuronal/genética , Extratos Vegetais/farmacologia , Hiperplasia Prostática/etiologia , Hiperplasia Prostática/prevenção & controle , Selênio/farmacologia , Compostos de Selênio/farmacologia , Serenoa/química , SurvivinaRESUMO
Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Sistema Endócrino/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Dutasterida/uso terapêutico , Sistema Endócrino/efeitos dos fármacos , Finasterida/uso terapêutico , Humanos , Masculino , Quinazolinas/uso terapêutico , Sulfonamidas/uso terapêutico , Tansulosina , Agentes Urológicos/uso terapêuticoRESUMO
We investigated the role of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome during testis ischemia and reperfusion injury (TI/R) in wild-type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular ischemia followed by 4 hours and 1 and 7 days of reperfusion or a sham TI/R. Furthermore, two groups of WT mice were treated at the beginning of reperfusion and up to 7 days with two inflammasome inhibitors, BAY 11-7082 (20 mg/kg i.p.) or Brilliant Blue G (45.5 mg/kg i.p.), or vehicle. Animals were killed with a pentobarbital sodium overdose at 4 hours and 1 and 7 days, and bilateral orchidectomies were performed. Biochemical and morphologic studies were carried out in all groups. TI/R in WT mice significantly increased caspase-1 and interleukin (IL)-1ß mRNA after 4 hours and IL-18 mRNA at 1 day of reperfusion (P ≤ 0.05). There was also a significant increase in caspase-3 and terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling-positive cells, marked histologic damage, and altered spermatogenesis in WT mice in both testes after 1 and 7 days of reperfusion. KO TI/R mice, WT TI/R BAY 11-7082, and Brilliant Blue G treated mice showed a significant reduced IL-1ß and IL-18 mRNA expression, blunted caspase-1 and -3 expression, minor histologic damages, low terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling activity, and preserved spermatogenesis. These data suggest that the activation of NLRP3 plays a key role in TI/R, and its inhibition might represent a therapeutic target for the management of patients with unilateral testicular torsion.
Assuntos
Proteínas de Transporte/genética , Inflamassomos/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Espermatogênese/genética , Doenças Testiculares/genética , Doenças Testiculares/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 1/metabolismo , Caspase 3/metabolismo , Interleucina-18/biossíntese , Interleucina-1beta/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Nitrilas/farmacologia , Orquiectomia , Corantes de Rosanilina/farmacologia , Sulfonas/farmacologia , Testículo/patologiaRESUMO
Recent studies have found that the inactivation of small hyaluronan (HA) fragments originating from native HA during inflammation reduced the inflammatory response in models of experimental arthritis. The stimulation of adenosine receptors A2A reduced inflammation by inhibiting NF-kB activation. The combination of both treatments was significantly more effective than either of the individual treatments. The aim of this study was to further investigate the effects of a combined treatment using the HA inhibitor Pep-1 and a selective A2AR agonist (CV-1808) on the structure and ultrastructure of the articular cartilage and on apoptosis in a model of collagen-induced arthritis (CIA) in mice. Arthritic mice were treated with Pep-1 and/or CV-1808 intraperitoneally daily for 20 days. At day 35, the hind limbs were processed for light microscopy (hematoxylin/eosin and Safranin-O-Fast Green) and for transmission and scanning electron microscopy. CIA increased IL-6, caspase-3 and caspase-7 mRNA expression and the related protein levels in arthritic articular cartilage, and significantly increased concentrations of Bcl-2-associated X protein (Bax), while B cell-lymphoma-2 protein (Bcl-2) was markedly reduced. The combined Pep-1/CV-1808 treatment significantly reduced CIA injury, particularly at the highest doses, demonstrated by the presence of Safranin-O-positive cartilage, with a smooth surface and normal chondrocytes in the superficial, intermediate and deep zones. Morphological data and histological scoring were strongly supported by the reduction in inflammation and apoptotic markers. The results further support the role of HA degradation and A2A receptors in arthritis.
Assuntos
Agonistas do Receptor A2 de Adenosina/farmacologia , Adenosina/análogos & derivados , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Artrite Experimental/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Ácido Hialurônico/antagonistas & inibidores , Articulações/efeitos dos fármacos , Peptídeos/farmacologia , Receptor A2A de Adenosina/efeitos dos fármacos , Adenosina/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Cartilagem Articular/metabolismo , Cartilagem Articular/ultraestrutura , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Colágeno Tipo II , Quimioterapia Combinada , Adjuvante de Freund , Ácido Hialurônico/metabolismo , Mediadores da Inflamação/metabolismo , Articulações/metabolismo , Articulações/ultraestrutura , Masculino , Camundongos Endogâmicos DBA , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Receptor A2A de Adenosina/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
OBJECTIVE: To demonstrate the corneal morphologic aspects obtained with in vivo confocal microscopy (CM) and light and electron microscopy of specimens obtained from the same patients with macular corneal dystrophy (MCD). DESIGN: Case series. PARTICIPANTS: Five consecutive patients affected by MCD undergoing penetrating keratoplasty (PK) in 1 eye. METHODS: The patients were examined with the slit-lamp, optical pachymetry, and CM before undergoing PK. The corneal buttons were processed for light, transmission, and scanning electron microscopy. MAIN OUTCOME MEASURES: Corneal in vivo CM, corneal light, and electron microscopy. RESULTS: Confocal microscopy showed areas of altered reflectivity in basal epithelial cells, which appeared hyperreflective or completely white. In the anterior stroma, rectilinear hyperreflective areas were shown. The stroma was characterized by a granular appearance of both keratocytes and extracellular matrix. Dark striae of different length and orientation were present in the middle and posterior stroma. The corneal endothelium showed polymegethism and cells containing bright granules in their cytoplasm. The histopathologic study demonstrated areas of thickened Bowman's layer covered by an epithelium reduced in height. The Bowman's layer thickenings were due to the accumulation of free or vesiculated material of different electron density. The keratocytes showed intracytoplasmatic vesicles, whereas the extracellular matrix presented a large quantity of intercellular electron-lucent material and parallel lamellae with an undulated course. Occasional macrophages, filled with vesicles of granular-filamentous material and evident podosomes, were observed. Descemet's membrane was formed by a normal anterior banded zone and a posterior nonbanded zone of honeycombed aspect. The endothelial cells showed a large number of intracytoplasmic vesicles. CONCLUSIONS: The structural changes observed with the histopathologic methods give an account and provide an explanation for the pathologic changes demonstrated by CM in the course of MCD. This may contribute to the understanding of in vivo imaging, allowing a better, noninvasive study of the disease evolution.
Assuntos
Córnea/ultraestrutura , Distrofias Hereditárias da Córnea/patologia , Microscopia Confocal , Adulto , Distrofias Hereditárias da Córnea/cirurgia , Paquimetria Corneana , Feminino , Humanos , Ceratoplastia Penetrante , Masculino , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Acuidade Visual/fisiologiaRESUMO
BACKGROUND: Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. CASE PRESENTATION: An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. CONCLUSIONS: The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.
Assuntos
Insuficiência Adrenal/diagnóstico , Túnica Conjuntiva/patologia , Ceratócitos da Córnea/patologia , Síndromes do Olho Seco/diagnóstico , Epitélio Corneano/patologia , Acalasia Esofágica/diagnóstico , Lágrimas/química , Adolescente , Consanguinidade , Humanos , Itália , Masculino , Microscopia Confocal , Concentração Osmolar , Acuidade VisualRESUMO
PURPOSE: Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. METHODS: Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. RESULTS: In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. CONCLUSIONS: Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.
Assuntos
Epitélio Corneano/citologia , Epitélio Corneano/efeitos dos fármacos , Trealose/farmacologia , Adulto , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/ultraestrutura , Epitélio Corneano/ultraestrutura , Feminino , Humanos , Técnicas In Vitro , Masculino , Microscopia Eletrônica de Transmissão , Adulto JovemRESUMO
Sigma-1 receptor (σ-1R) modulates cellular signaling pathways, probably acting as a ligand operated chaperone. When activated, the receptor translocates from the interface mitochondrion associated membrane of the endoplasmic reticulum to the cell membrane. σ-1R was demonstrated in some brain regions, including the pineal gland, and was proposed to be involved in several cerebral processes, including neuroprotective responses against homeostasis alterations. On this basis, the immunohistochemical expression of σ-1R in human pineal glands was evaluated, with particular regard to the different causes of death. Thirty-eight pineal glands obtained from forensic autopsies were divided into five groups according to the cause of death: sudden death, drowning, fire fatality, hanging, and hemorrhagic shock, and examined with hematoxylin-eosin stain and immunohistochemistry for σ-1R. Both pinealocytes and perivascular spaces were evaluated. The pineal glands from sudden death were only mildly positive for σ-1R, while a more evident immunopositivity was observed in hanging, fire fatality, hemorrhagic shock, and drowning. These results were confirmed in a two-by-two comparison between the sudden death group and other groups. Our data demonstrate for the first time with immunohistochemical techniques the presence of σ-1R expression in the human pineal gland and propose a direct correlation between σ-1R expression and duration of the death process, in particular when hypoxic conditions and/or excessive psychological stress are present.
Assuntos
Causas de Morte , Imuno-Histoquímica , Glândula Pineal , Receptores sigma , Receptor Sigma-1 , Humanos , Receptores sigma/metabolismo , Glândula Pineal/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Patologia Legal , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
Diabetic mice are characterized by a disrupted expression pattern of VEGF (vascular endothelial growth factor), and impaired vasculogenesis during healing. Experimental evidence suggests that RLX (relaxin) can improve several parameters associated with wound healing. Therefore we investigated the effects of porcine-derived RLX in diabetes-related wound-healing defects in genetically diabetic mice. An incisional wound model was produced on the back of female diabetic C57BL/KsJ-m+/+Lept(db) (db+/db+) mice and their normal littermates (db(+/+)m). Animals were treated daily with porcine RLX (25 µg/mouse per day, subcutaneously) or its vehicle. Mice were killed on 3, 6 and 12 days after skin injury for measurements of VEGF mRNA and protein synthesis, SDF-1α (stromal cell-derived factor-1α) mRNA and eNOS (endothelial NO synthase) expression. Furthermore, we evaluated wound-breaking strength, histological changes, angiogenesis and vasculogenesis at day 12. Diabetic animals showed a reduced expression of VEGF, eNOS and SDF-1α compared with non-diabetic animals. At day 6, RLX administration resulted in an increase in VEGF mRNA expression and protein wound content, in eNOS expression and in SDF-1α mRNA. Furthermore, the histological evaluation indicated that RLX improved the impaired wound healing, enhanced the staining of MMP-11 (matrix metalloproteinase-11) and increased wound-breaking strength at day 12 in diabetic mice. Immunohistochemistry showed that RLX in diabetic animals augmented new vessel formation by stimulating both angiogenesis and vasculogenesis. RLX significantly reduced the time to complete skin normalization and this effect was abrogated by a concomitant treatment with antibodies against VEGF and CXCR4 (CXC chemokine receptor 4), the SDF-1α receptor. These data strongly suggest that RLX may have a potential application in diabetes-related wound disorders.
Assuntos
Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/genética , Relaxina/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Glicemia/metabolismo , Caderinas/metabolismo , Quimiocina CXCL12/metabolismo , Feminino , Metaloproteinase 11 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/genética , Óxido Nítrico/metabolismo , Relaxina/farmacologia , Suínos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
AIM: The aim of the present study was to propose the clinical efficacy of the different dentin matrix obtained from three devices (BonMaker, Tooth Transformer, and Smart Dentin Grinder) and to show their morphological, physical, and biochemical characteristics using scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, and Raman spectroscopy. RESEARCH DESIGN AND METHODS: The study included 70 patients who underwent bone augmentation using the BonMaker, Tooth Transformer, and Smart Dentin Grinder devices. In addition, 84 implants were placed. Furthermore, four samples, one for each device and one non-demineralized control, were analyzed with scanning electron microscopy (SEM), energy-dispersive X-ray analysis, and Raman spectroscopy. RESULTS: In all patients, augmentation of bone defects with ground dentin matrix was successful, and implants showed correct osseointegration. The morphological organization, the chemical composition, and the presence of organic molecules in the dentin samples processed by the three different devices were demonstrated using SEM, energy-dispersive X-ray analysis, and Raman spectroscopy. CONCLUSIONS: Comparing BonMaker, Tooth Transformer, and Smart Dentin Grinder devices in our practice, we concluded that these systems, even with different structural and chemical differences of the dentin granules, have a comparable potential for obtaining regenerative material from the patient's own teeth.
Assuntos
Materiais Biocompatíveis , Dentina , Humanos , Dentina/química , Microscopia Eletrônica de Varredura , Osso e Ossos , Resultado do TratamentoRESUMO
Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is the kidney, where it accumulates. In the present narrative review, we assessed experimental and clinical data dealing with the mechanisms of kidney morphological and functional damage caused by Cd and the state of the art about possible therapeutic managements. Intriguingly, skeleton fragility related to Cd exposure has been demonstrated to be induced both by a direct Cd toxic effect on bone mineralization and by renal failure. Our team and other research groups studied the possible pathophysiological molecular pathways induced by Cd, such as lipid peroxidation, inflammation, programmed cell death, and hormonal kidney discrepancy, that, through further molecular crosstalk, trigger serious glomerular and tubular injury, leading to chronic kidney disease (CKD). Moreover, CKD is associated with the presence of dysbiosis, and the results of recent studies have confirmed the altered composition and functions of the gut microbial communities in CKD. Therefore, as recent knowledge demonstrates a strong connection between diet, food components, and CKD management, and also taking into account that gut microbiota are very sensitive to these biological factors and environmental pollutants, nutraceuticals, mainly present in foods typical of the Mediterranean diet, can be considered a safe therapeutic strategy in Cd-induced kidney damage and, accordingly, could help in the prevention and treatment of CKD.
RESUMO
In the original publication [...].