RESUMO
The neurodegenerative condition FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS), with polymer deposition within the endoplasmic reticulum (ER) of neurons. We generated transgenic neural progenitor cells (NPCs) from mouse fetal cerebral cortex stably expressing either the control protein GFP or human wild type, polymerogenic G392E or truncated (delta) NS. This cellular model makes it possible to study the toxicity of polymerogenic NS in the appropriated cell type by in vitro differentiation to neurons. Our previous work showed that expression of G392E NS in differentiated NPCs induced an adaptive response through the upregulation of several genes involved in the defence against oxidative stress, and that pharmacological reduction of the antioxidant defences by drug treatments rendered G392E NS neurons more susceptible to apoptosis than control neurons. In this study, we assessed mitochondrial distribution and found a higher percentage of perinuclear localisation in G392E NS neurons, particularly in those containing polymers, a phenotype that was enhanced by glutathione chelation and rescued by antioxidant molecules. Mitochondrial membrane potential and contact sites between mitochondria and the ER were reduced in neurons expressing the G392E mutation. These alterations were associated with a pattern of ER stress that involved the ER overload response but not the unfolded protein response. Our results suggest that intracellular accumulation of NS polymers affects the interaction between the ER and mitochondria, causing mitochondrial alterations that contribute to the neuronal degeneration seen in FENIB patients.
Assuntos
Antioxidantes , Neurônios , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Estresse do Retículo Endoplasmático , Epilepsias Mioclônicas , Transtornos Heredodegenerativos do Sistema Nervoso , Humanos , Camundongos , NF-kappa B/metabolismo , Neurônios/metabolismo , Neuropeptídeos , Polímeros , Serpinas , NeuroserpinaRESUMO
INTRODUCTION: A patient undergoing renal transplantation presents unique problems to the anesthetist, as almost every body system is affected. The combined spinal-epidural technique has become popular in lower abdominal surgeries because it offers the advantages of both spinal and epidural techniques. We review our experience of combined spinal-epidural technique in patients undergoing renal transplantation with respect to demographics, intraoperative anesthesia, hemodynamics, postoperative analgesia, and untoward adverse events. MATERIALS AND METHOD: Fifty consecutive patients scheduled for elective renal transplantation over a period of 4 months who consented for combined spinal-epidural anesthesia were enrolled in the study. Combined spinal-epidural anaesthesia was performed using a double-space technique in the right lateral position. Intraoperative monitoring included electrocardiography, pulse oximetry, noninvasive blood pressure, central venous pressure, and urinary output after clamp release. Intravenous fluids, colloids, and blood products were infused so as to keep the central venous pressure between 12 and 15 mm Hg. Postoperative analgesia was provided with buprenorphine via an epidural catheter. We noted intraoperative and postoperative complications. RESULTS: Neuraxial blockade was satisfactory in all but four patients who required supplementation with general anesthesia for unduly prolonged surgery. There were no significant intraoperative hemodynamic changes. The total intravenous fluid used during surgery was 64.24 +/- 12.3 mL/kg. During the postoperative period, all patients had good postoperative pain relief with no incidence of epidural hematoma. CONCLUSION: Combined spinal-epidural anesthesia proved to be a useful regional anesthetic technique, combining the reliability of spinal block and versatility of epidural block for renal transplantation.
Assuntos
Anestesia Epidural/métodos , Raquianestesia/métodos , Transplante de Rim/métodos , Adulto , Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Pressão Sanguínea , Bradicardia/prevenção & controle , Bupivacaína/uso terapêutico , Feminino , Humanos , Hipotensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Período Pós-OperatórioRESUMO
BACKGROUND: Appropriate anesthesia for pediatric renal transplantation requires stable intraoperative hemodynamics, optimal perfusion of the newly transplanted kidney and good analgesia during recovery. The aim of this study was to assess the preliminary application, success and safety of combined epidural and general anesthesia in pediatric renal transplantation in a small cohort. METHODS: We retrospectively reviewed the anesthesia records of 46 consecutive pediatric patients who received renal transplantation under combined epidural and general anesthesia from January 2003-2007. RESULTS: The mean patient age and weight were 13.2 +/- 2.4 years and 25.7 +/- 5.46 kg, respectively. The infused crystalloids, 20% albumin and red blood cell concentrates were 120 +/- 2 mL/kg to achieve a CVP of 13 to 15 mm Hg. Brisk diuresis was observed in all patients. Epidural tramadol (2 mg/kg) provided good postoperative analgesia in 89% patients. 15% patients developed radiological evidence of pulmonary edema, only one required mechanical ventilation for hypoxemia. Minor adverse effects were nausea and vomiting (17.5%) and convulsions (8.5%). No perioperative mortality or major morbidity was recorded. CONCLUSION: Epidural anesthesia is a useful adjunct to general anesthesia due to stable intraoperative haemodynamics and good postoperative analgesia.
Assuntos
Anestesia Epidural , Anestesia Geral , Transplante de Rim/métodos , Adolescente , Analgésicos/uso terapêutico , Criança , Terapia Combinada , Feminino , Humanos , Período Intraoperatório , Nefropatias/classificação , Nefropatias/cirurgia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Estudos Retrospectivos , Vômito/prevenção & controleRESUMO
In a developing country such as India, cadaveric renal transplantation accounts for only less than 1% of total renal transplantations. The reasons for such a low rate of cadaveric transplantation are many, ranging from lack of awareness to socioeconomic reasons. Our institute conducted a statewide public awareness program and initiated an intercity organ harvesting program. This doubled the cadaveric renal transplantations in the last 2 years. We performed 38 cadaveric transplantations among 190 renal transplantations in the last year (August 2005 to July 2006). We retrieved kidneys from 21 donors, of whom 9 were outside our city. From 21 donors we transplanted 38 recipients; out of whom 3 received dual kidneys and one kidney was discarded. The Mean age of the donors was 41.4 +/- 18.2 years with a mean cold ischemia time of 6.9 +/- 3.8 hours. Sixty-eight percent had delayed graft function. At the last follow-up, which was 190 +/- 98 days, patient survival rate was 90%: 4 patients died, including 2 due to bacterial sepsis and 2 due to cytomegalovirus (CMV) disease. The Graft survival rate was 85%, and the death-censored graft survival rate was 90%. Mean serum creatinine value at the last follow-up was 1.2 +/- 0.3 mg%. There were 5 episodes of acute rejection in 31 patients during first 3 months (16% acute rejection rate). The increase in cadaveric transplantations was associated with satisfactory patient and graft survival despite the high incidence of delayed graft function.
Assuntos
Transplante de Rim/estatística & dados numéricos , Adulto , Cadáver , Países em Desenvolvimento , Humanos , Índia , Pessoa de Meia-Idade , Doadores de Tecidos , Coleta de Tecidos e Órgãos/métodosRESUMO
In a developing country such as India, deceased donor renal transplantation (DDRTx) accounts for only about 1% of all renal transplants (RTx). Our institute initiated an intercity DDRTx in the year 2006, which significantly increased the number of RTx. We retrieved 74 kidneys from 37 deceased donors from various cities of Gujarat from January 2006 to December 2009. We transplanted the allografts in 66 recipients and a retrospective analysis of the donor profile and management and recipient outcome was performed. The mean age of the donors was 43.3 ± 18.8 years. The causes of death included road traffic accident in 51.35% of the donors and cerebrovascular stroke in 48.65% of the donors; 83.78% of the donors required ionotropes for hemodynamic stability in addition to vigorous intravenous fluid replacement. The average urine output of the donors was 350 ± 150 mL. The organs were perfused and stored in HTK solution. The mean cold ischemia time (CIT) was 9.12 ± 5.25 h. The mean anastomosis time in the recipient was 30.8 ± 8.7 min. 57.6% of the recipients established urine output on the operating table and 42.4% developed delayed graft function. At the end of 1 month after transplantation, the mean serum creatinine was comparable to the Ahmadabad city DDRTx, although the CIT was significantly longer in the intercity patients. Intercity organ harvesting is a viable option to increase the donor pool. Distance may not be an impediment, and good recipient outcome is possible in spite of prolonged CIT in case of proper harvesting and preservation.
Assuntos
Transplante de Rim , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/organização & administração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Transcervical resection of endometrium is an alternative to hysterectomy for women with menorrhagia. The procedure involves the use of cutting loop diathermy to resect the endometrium while the uterine cavity is irrigated with 1.5% glycine which can absorb consequent fluid and electrolyte shifts. Severe hyponatremia leading to central pontine myelinolysis is an extremely rare complication of this procedure. We report a case of a young female undergoing transcervical resection of endometrium for menorrhagia, who developed central pontine myelinolysis but made a complete recovery after three months.