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1.
Regen Ther ; 27: 506-518, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38745839

RESUMO

Introduction: Acute kidney injury (AKI) is a common health problem that leads to high morbidity and potential mortality. The failure of conventional treatments to improve forms of this condition highlights the need for innovative and effective treatment approaches. Regenerative therapies with Renal Progenitor Cells (RPCs) have been proposed as a promising new strategy. A growing body of evidence suggests that progenitor cells differentiated from different sources, including human embryonic stem cells (hESCs), can effectively treat AKI. Methods: Here, we describe a method for generating RPCs and directed human Embryoid Bodies (EBs) towards CD133+CD24+ renal progenitor cells and evaluate their functional activity in alleviating AKI. Results: The obtained results show that hESCs-derived CD133+CD24+ RPCs can engraft into damaged renal tubules and restore renal function and structure in mice with gentamicin-induced kidney injury, and significantly decrease blood urea nitrogen levels, suppress oxidative stress and inflammation, and attenuate histopathological disturbances, including tubular necrosis, tubular dilation, urinary casts, and interstitial fibrosis. Conclusion: The results suggest that RPCs have a promising regenerative potential in improving renal disease and can lay the foundation for future cell therapy and disease modeling.

2.
Exp Cell Res ; 434(2): 113875, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38092345

RESUMO

The mammalian renal organ represents a pinnacle of complexity, housing functional filtering units known as nephrons. During embryogenesis, the depletion of niches containing renal progenitor cells (RPCs) and the subsequent incapacity of adult kidneys to generate new nephrons have prompted the formulation of protocols aimed at isolating residual RPCs from mature kidneys and inducing their generation from diverse cell sources, notably pluripotent stem cells. Recent strides in the realm of regenerative medicine and the repair of tissues using stem cells have unveiled critical signaling pathways essential for the maintenance and generation of human RPCs in vitro. These findings have ushered in a new era for exploring novel strategies for renal protection. The present investigation delves into potential transcription factors and signaling cascades implicated in the realm of renal progenitor cells, focusing on their protection and differentiation. The discourse herein elucidates contemporary research endeavors dedicated to the acquisition of progenitor cells, offering crucial insights into the developmental mechanisms of these cells within the renal milieu and paving the way for the formulation of innovative treatment modalities.


Assuntos
Rim , Células-Tronco Pluripotentes , Animais , Humanos , Diferenciação Celular , Medicina Regenerativa , Transdução de Sinais , Mamíferos
3.
Anat Cell Biol ; 57(1): 70-84, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37994041

RESUMO

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

4.
Craniomaxillofac Trauma Reconstr ; 16(3): 205-210, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37975031

RESUMO

Study Design and Objectives: This study aimed to investigate Triamcinolone ointment's effect on pain and bleeding after tonsillectomy by suturing method. Methods: The present study was performed as a single-blind clinical trial on 200 patients who underwent a total tonsillectomy in the ENT department of Loghman Hakim Hospital in Tehran during 2016. Candidates for total tonsillectomy were randomized into 2 groups one by one. Participants were randomly divided into 2 groups. Both groups matched homologically. Patients in both groups (intervention and control) underwent cold dissection total tonsillectomy. In addition to suturing, in the intervention group, Triamcinolone ointment was used to control the local bleeding at the surgical site. In the control group, only sutures were used to control bleeding. The studied variables included: bleeding and pain 24 hours after surgery, Time to start oral feeding. Result: The frequency of bleeding cases in the first 24 hours are included: 4 patients (5.63%) in the intervention group and 6 patients (8.45%) in the control group (P = 0.01). The average time to start eating for patients who were treated with topical triamcinolone ointment was significantly less than those who were not treated with this ointment. Only 2 patients (2.77%) in the intervention group took analgesics in the first 24 hours after surgery, while and 11 patients (15.3%) in the control group received analgesics in the same time period. Conclusion: In general, the results of this study showed that the use of Triamcinolone ointment in total tonsillectomy could reduce bleeding, analgesics usage, and the time of feeding onset.

5.
Acta Neurobiol Exp (Wars) ; 83(4): 414-431, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38224280

RESUMO

Methamphetamine (METH) is a highly addictive psychostimulant known for its profound impact on the nervous system. Chronic METH use leads to neurotoxicity characterized by various molecular and structural alterations in the brain. This review article primarily aims to elucidate the mechanisms underlying METH­induced neurotoxicity. METH's mechanism of action involves the inhibition of dopamine, serotonin, and norepinephrine reuptake, resulting in altered synaptic function. Prolonged METH exposure triggers oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, impaired axonal transport, autophagy, and programmed cell death, ultimately contributing to neurotoxicity. These neurotoxic effects manifest as increased neuronal firing rate, disruptions in intracellular ion balance (Ca2+ and Na+), energy production imbalances, and excessive reactive oxygen species production. The blood­brain barrier is compromised, leading to structural, functional, and neurochemical alterations, particularly in the fronto­striatal circuit. While our comprehensive review addresses these intricate molecular and structural changes induced by METH, we also examined the latest therapeutic strategies designed to mitigate neurotoxicity. Our investigation sheds light on the critical need to comprehend the complex pathways underlying METH­induced neurotoxicity and develop effective treatment approaches.


Assuntos
Estimulantes do Sistema Nervoso Central , Metanfetamina , Síndromes Neurotóxicas , Humanos , Metanfetamina/toxicidade , Síndromes Neurotóxicas/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/toxicidade , Inflamação , Apoptose
6.
Neurochem Res ; 43(12): 2313-2323, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30288644

RESUMO

Parkinson's disease is the second most common neurodegenerative disease that occurs due to cellular autophagy deficiency and the accumulation of alpha-synuclein in the dopaminergic neurons of the substantia nigra pars compacta (SNc) of the brainstem. The SMER28 (also known as 6-Bromo-N-prop-2-enylquinazolin-4-amine) is an autophagy inducer. In this study, the neuroprotective effects of SMER28 were evaluated on autophagy induction, antioxidant system activation, and microgliosis attenuation. The Parkinson's disease model was developed in the male Wistar rats by injection of 6-OHDA into the left striatum. Apomorphine-induced behavior assessment test and SNc cell counting were performed to investigate the neuroprotective effects of SMER28. This study examined the pharmacological roles of SMER28, especially by focusing on the autophagy (p62/ SQSTM1 and LC3II/LC3I ratio where LC3 is microtubule-associated protein 1A/1B-light chain 3), inhibiting free radicals, and activating the antioxidant system. The levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), GSH/glutathione peroxidase (GPX), superoxide dismutase (SOD) activity and nuclear factor-erythroid 2-related factor-2 (Nrf2) were measured to evaluate the antioxidant activity of SMER28. Moreover, Iba-1 (ionized calcium binding adaptor molecule, indicating microgliosis) and tyrosine hydroxylase immunoreactivities were evaluated in the SNc. In the behavioral assessment, SMER28 (50 µg/kg) attenuated damages to the SNc dopaminergic neurons, characterized by improved motor function. The tissue observations revealed that SMER28 prevented the destruction of SNc neurons and attenuated microgliosis as well. It also reduced MDA and ROS production and increased GSH, GPX, SOD, and Nrf2 activities by inducing autophagy (decreasing p62 and increasing LC3II/LC3I ratio). Consequently, possibly with further studies, it can be considered as a drug for neurodegenerative diseases with proteinopathy etiology.


Assuntos
Compostos Alílicos/uso terapêutico , Autofagia/fisiologia , Estresse Oxidativo/fisiologia , Oxidopamina/toxicidade , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/prevenção & controle , Quinazolinas/uso terapêutico , Compostos Alílicos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Dopamina/toxicidade , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Quinazolinas/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar
7.
Neural Regen Res ; 13(1): 154-160, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29451220

RESUMO

Previous animal studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling pathway plays an important role in the targeted migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the injured area. In the present study, we aimed to investigate the potential role of chemotactic SDF-1/CXCR4 signaling pathway in the homing of transplanted BMSCs to the injured cochlea after noise-induced hearing loss (NIHL) in a rat model. White noise exposure (110 dB) paradigm was used for hearing loss induction in male rats for 6 hours in 5 days. Distortion-product otoacoustic emission (DPOAE) responses were recorded before the experiment and post noise exposure. Hoechst 33342-labeled BMSCs and CXCR4 antagonist (AMD3100)-treated BMSCs were injected into the rat cochlea through the round window. SDF-1 protein expression in the cochlear tissue was assayed using western blot assay. The number of labeled BMSCs reaching the endolymph was determined after 24 hours. SDF-1 was significantly increased in the cochlear tissue of rats in the noise exposure group than in the control group. The number of Hoechst 33342-labeled BMSCs reaching the endolymph of the cochlea was significantly smaller in the AMD3100-treated BMSCs group than in the normal BMSCs group. Our present findings suggest that the SDF-1/CXCR4 signaling pathway has a critical role in BMSCs migration to the injured cochlea in a rat model of noise-induced hearing loss.

8.
Behav Brain Res ; 324: 71-76, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28212940

RESUMO

Many studies have been shown that maternal stress during pregnancy and in early life period influences offspring in the behavioral and molecular aspects in human and animal models. Recent research has indicated that the environmental condition of males before conception has effects on next generations. We evaluated whether preconception paternal stress (PPS) could influence on hippocampal glucocorticoid receptor gene (GR), (NR3C1) expression, corticosterone response and behavioral outcomes of their offspring. For this purpose, adult male rats were subjected to daily 10min session of forced swimming for 21 consecutive days. Then, two parental breeding groups were formed: stressed father (SF) and non-stressed father (NSF) or control group. 30-day-old pups were tested for anxiety-like behavior by using the elevated plus maze (EPM). Serum corticosterone level was also measured by ELISA. Hippocampal NR3C1 DNA methylation, gene and protein expression were respectively assayed by methylation sensitive restriction enzymes (Real Time PCR), Reverse Transcriptase PCR (RT-PCR) and Western-blotting in all groups. More anxiety-related behavior, serum corticosterone concentration, DNA methylation levels of NR3C1 and lower expression of this gene were significantly observed in paternally stressed pups compared to control pups. As well, molecular changes were more pronounced in male pups compared to female pups. Our results revealed that paternal stress prior to conception has a negative effect on molecular, hormonal and behavioral outcomes in their offspring.


Assuntos
Metilação de DNA , Hipocampo/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores de Glucocorticoides/metabolismo , Estresse Psicológico/metabolismo , Animais , Ansiedade/metabolismo , Corticosterona/sangue , Epigênese Genética , Feminino , Masculino , Gravidez , RNA Mensageiro/metabolismo , Ratos Wistar
9.
J Otol ; 10(1): 18-20, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29937777

RESUMO

BACKGROUND: The measurement of the piston length during stapedotomy is important and it may have significant effects on the surgical outcome. OBJECTIVE: To determine the piston length in a group of otosclerosis patients who underwent primary stapedotomy. MATERIAL AND METHODS: Between Sep 2013 and Sep 2014, 85 patients with diagnosed otosclerosis underwent primary stapedotomy. Teflon prosthesis of 0.6 mm of diameter was used in all patients. The distance between medial surface of the long process of incus and center point of the stapedial footplate measured. The piston length calculated by adding 0.25 mm for the thickness of footplate and 0.50 mm for placement of the prosthesis into the vestibule. RESULTS: The distance between stapedial foot plate and incus ranged from 3.50 to 4.50 mm. The mean distance was 3.95 ± 0.16 mm. In majority of cases (74.1%) piston length was 4.75 mm followed by 4.50 mm in 15.3% and 5.00 mm in 5.9%. Piston length was 4.25 mm in 3.5% and 5.25 mm in only 1.2% of patients. There was no significant post-operative complication and air bone gap closure obtained in all patients. CONCLUSION: The most common distance between foot plate and incus is 4.00 mm. No case needed a piston longer than 5.25 mm or shorter than 4.25 mm.

10.
Am J Forensic Med Pathol ; 34(1): 5-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23361069

RESUMO

Treatment of nasal obstruction with conventional septoplasty is a very common operation in otorhinolaryngology. There are considerable complications that may become even life threatening. We report a rare complication of septoplasty, namely, skull base injury. The possible mechanisms and treatment modality are discussed. Like other similar procedures, prevention of the skull base injury is more important than its treatment. Correct knowledge about anatomy of the region and meticulous manipulation and instrumentation are the most considerable topics.


Assuntos
Osso Etmoide/lesões , Osso Etmoide/patologia , Complicações Intraoperatórias , Septo Nasal/cirurgia , Fraturas Cranianas/patologia , Adolescente , Encefalocele/patologia , Patologia Legal , Humanos , Hidrocefalia/patologia , Hemorragias Intracranianas/patologia , Masculino , Obstrução Nasal/cirurgia , Pneumocefalia/patologia , Complicações Pós-Operatórias , Fraturas Cranianas/etiologia
11.
Auris Nasus Larynx ; 40(2): 177-83, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22854054

RESUMO

OBJECTIVE: To define anatomical variations that may lead to rhinogenic contact point headache. METHODS: Paranasal sinuses CT scan and medical records of sixty-five patients who underwent a successful endoscopic surgery for rhinogenic contact point headache reviewed. RESULTS: Eleven distinct anatomical variations were found in patients with rhinogenic contact point headache. All of them were surgically curable. CONCLUSION: There are multiple anatomical situations that may lead to rhinogenic contact point headache and each one has its own characteristics. Treatment plan should be personalized for every patient considering the diagnosed anatomical variation.


Assuntos
Cefaleia/etiologia , Nariz/diagnóstico por imagem , Seios Paranasais/diagnóstico por imagem , Adulto , Variação Anatômica , Feminino , Cefaleia/diagnóstico por imagem , Cefaleia/cirurgia , Humanos , Masculino , Nariz/cirurgia , Seios Paranasais/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
12.
Indian J Otolaryngol Head Neck Surg ; 65(Suppl 2): 216-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24427649

RESUMO

To determine the effectiveness of dexamethasone to reduce pain, nausea and vomiting after septoplasty. Study is a prospective double-blind randomized controlled trial. A total of 90 patients were enrolled and received an either of dexamethasone or placebo in the induction of anesthesia. The patients were asked to note the level of pain on the visual analogue scale in the first 24 h after surgery. They also had to record their severity of nausea and number of vomiting attacks. There were statistically significant differences between the two groups for the level of pain noted on the visual analogue scale. The severity of nausea was lower after treatment with dexamethasone but the difference between two groups was not significant. There was also a significant decrease in the number of vomiting attacks in patients treated with dexamethasone. A single dose of 8 mg of dexamethasone, given intravenously, at induction of anesthesia for septoplasty significantly decreased the pain, post-operative nausea and vomiting for the day of operation.

13.
Indian J Otolaryngol Head Neck Surg ; 65(Suppl 3): 537-40, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24427710

RESUMO

End stage renal failure patients, face to multiple complications. One of them is the involvement of auditory system. There are several proposed mechanisms for occurrence of hearing loss in these patients. There is no study performed in Iran for determining the status of hearing loss and results of audiometric tests in chronic renal failure patients. To assess prevalence, type and accompanying factors of auditory complications in end stage renal disease patients. Seventy chronic renal failure patients underwent clinical examination and audiometric tests. Their medical records reviewed to find out any contributing factor with auditory complications. There was higher prevalence of sensory neural hearing loss in CRF patients. The hearing loss was more obvious in higher frequencies. Its prevalence and severity increased with chronicity of renal failure and hemodialysis. There was not any difference regarding the sex. The hearing loss did not disturbed speech discrimination score and acoustic reflex. Sensory-neural hearing loss is common among CRF patients and deserves more attention than is paid by current approaches.

14.
Eur Arch Otorhinolaryngol ; 266(2): 273-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18553093

RESUMO

The purpose of this study was to review our recent experience with deep neck infections and compare it to the experiences in the available literature. A total number of 112 charts of patients treated for deep neck infections at the department of otolaryngology of our hospital between August 1996 and September 2007 were retrospectively reviewed. All the relevant clinical charts including presentation, origin and site of deep neck infection, radiological, and bacteriological studies and interventions along with demographic profile, details of hospital stay, and outcomes were evaluated. The findings were compared to those in the available literature. Until 2002, we had nearly constant number of patients annually but since then we have found an increasing number of them. The most common presenting symptom was neck swelling (88.4%). Fever was present in 63.4 and 78% had leukocytosis. The most common known cause was dental infection (31.3%) and in 32.1% of them origin remained unknown. The most commonly encountered site was the submandibular space and 23.2% of patients had two or more involved spaces. Exactly 20.5% were treated with intravenous antibiotic therapy alone whereas 79.5% had surgical procedures with successful results in 98.2% of them. Diabetes mellitus was diagnosed in 20.5% of cases. There was no case of known primary or acquired immunodeficiency. We had two deaths from septic shock but there was not any other complication. Mean hospitalization time was 7 days. Deep neck infections remain potentially lethal infections if they are not diagnosed early and treated promptly. Widespread diffusion of empirical broad-spectrum oral antibiotic and anti-inflammatory treatments may cause masked presentations of deep neck infections without swelling, fever, or leukocytosis. Our tailored approach (medical or medical and surgical) based on clinical and radiological evidence was successful in 98.2% of the patients with a short mean hospitalization time.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Pescoço , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/patologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Infecções Bacterianas/terapia , Criança , Pré-Escolar , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Hospitalização/tendências , Humanos , Incidência , Lactente , Irã (Geográfico)/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/terapia , Adulto Jovem
15.
Clin Infect Dis ; 37(7): e107-8, 2003 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-13130420

RESUMO

Disseminated Fusarium infection is a rare disease that is usually limited to immunocompromised patients. It more commonly occurs in patients with acute leukemia and prolonged neutropenia. We report a case of chronic Fusarium infection in an adult patient with undiagnosed chronic granulomatous disease (CGD), a primary immunodeficiency disorder in which phagocytic cells are defective in generating superoxide anion and its metabolites. The case is important because the patient had no manifestations of CGD until she was almost 60 years old and because this is, to our knowledge, the first reported case of Fusarium infection in a patient with CGD.


Assuntos
Fusarium , Doença Granulomatosa Crônica/complicações , Micoses/etiologia , Infecções Oportunistas/microbiologia , Feminino , Doença Granulomatosa Crônica/imunologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Micoses/microbiologia , Infecções Oportunistas/imunologia
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