RESUMEN
Paragangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the potential to metastasize. To date, molecular mechanisms of paraganglioma progression remain elusive. We report a case of a 38-year-old woman with metastatic CPGL manifesting as a recurrent tumor with lymph node metastasis. The tumor was fast-growing and had a high Ki-67 proliferation index. Immunohistochemical (IHC) examination and whole-exome sequencing were performed for both recurrent tumor and metastasis. A germline pathogenic splice acceptor variant in the SDHB gene was found in the patient. Immunoreactivity of the SDHB subunit was weak diffuse in both samples, indicating deficiency of the succinate dehydrogenase. Moreover, the recurrent tumor exhibited loss of heterozygosity (LOH) at the SDHB locus, that is according to Knudson's "two-hit" hypothesis of cancer causation. We also identified a rare somatic promotor mutation in the TERT gene associated with the tumor progression. Obtained results confirmed the indicative role of the germline SDHB mutation for metastatic CPGLs, as well as the potential prognostic value of the TERT promoter mutation.
Asunto(s)
Cuerpo Carotídeo/patología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Paraganglioma/diagnóstico , Paraganglioma/genética , Adulto , Biomarcadores de Tumor , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Pruebas Genéticas , Humanos , Inmunohistoquímica , Mutación , Paraganglioma/terapia , Succinato Deshidrogenasa/genética , Succinato Deshidrogenasa/metabolismoRESUMEN
Various authors have hypothesized carotid body (CB) involvement in Coronavirus Disease 2019 (COVID-19), through direct invasion or indirect effects by systemic stimuli ('cytokine storm', angiotensin-converting enzyme [ACE]1/ACE2 imbalance). However, empirical evidence is limited or partial. Here, we present an integrated histopathological and virological analysis of CBs sampled at autopsy from four subjects (2 males and 2 females; age: >70 years old) who died of COVID-19. Histopathological, immunohistochemical and molecular investigation techniques were employed to characterize Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV2) viral invasion and inflammatory reaction. SARS-CoV2 RNA was detected in the CBs of three cases through Real-Time Reverse Transcription Polymerase Chain Reaction (RT-PCR). In these cases, positive immunostaining for Nucleocapsid and Spike protein were also demonstrated, mainly at the level of large roundish cells consistent with type I cells, confirming direct CB invasion. In these cases, T lymphocytes showed focal aggregations in the CBs, suggestive of local inflammatory reaction. Blood congestion and microthrombosis were also found in one of the positive cases. Intriguingly, microthrombosis, blood congestion and microhaemorrages were also bilaterally detected in the CBs of the negative case, supporting the possibility of COVID-19 effects on the CB even in the absence of its direct invasion. SARS-CoV-2 direct invasion of the CB is confirmed through both immunohistochemistry and RT-PCR, with likely involvement of different cell types. We also reported histopathological findings which could be ascribed to local and/or systemic actions of SARS-CoV-2 and which could potentially affect chemoreception.
Asunto(s)
COVID-19 , Cuerpo Carotídeo , SARS-CoV-2 , Anciano , Autopsia , COVID-19/patología , COVID-19/virología , Cuerpo Carotídeo/patología , Cuerpo Carotídeo/virología , Proteínas de la Nucleocápside de Coronavirus/metabolismo , Femenino , Humanos , Masculino , Fosfoproteínas/metabolismo , ARN Viral/análisis , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/metabolismoRESUMEN
Carotid bodies (CBs) are chemoreceptors that monitor and register changes in the blood, including the levels of oxygen, carbon dioxide, and pH, and regulate breathing. Enhanced activity of CBs was shown to correlate with a significant elevation in the blood pressure of patients with hypertension. CB removal or denervation were previously shown to reduce hypertension. Here we demonstrate the feasibility of a dual-mode ultrasound array (DMUA) system to safely ablate the CB in vivo in a spontaneously hypertensive rat (SHR) model of hypertension. DMUA imaging was used for guiding and monitoring focused ultrasound (FUS) energy delivered to the target region. In particular, 3D imaging was used to identify the carotid bifurcation for targeting the CBs. Intermittent, high frame rate imaging during image-guided FUS (IgFUS) delivery was used for monitoring the lesion formation. DMUA imaging provided feedback for closed-loop control (CLC) of the lesion formation process to avoid overexposure. The procedure was tolerated well in over 100 SHR and normotensive rats that received unilateral and bilateral treatments. The measured mean arterial pressure (MAP) exhibited measurable deviation from baseline 2-4 weeks post IgFUS treatment. The results suggest that the direct unilateral FUS treatment of the CB might be sufficient to reduce the blood pressure in hypertensive rats and justify further investigation in large animals and eventually in human patients.
Asunto(s)
Cuerpo Carotídeo/cirugía , Ultrasonido Enfocado de Alta Intensidad de Ablación/instrumentación , Hipertensión/cirugía , Cirugía Asistida por Computador/instrumentación , Animales , Cuerpo Carotídeo/patología , Hipertensión/diagnóstico por imagen , Hipertensión/patología , Masculino , Ratas , Ratas Endogámicas SHR , Signos VitalesRESUMEN
Postmortem changes occurring in human carotid body were simulated on the Wistar rat model. It was shown that light, dark, and pyknotic (progenitor) subtypes of human carotid body cells are an artifact and cannot be used in clinical practice to study the characteristics of various human diseases. The differences between the control group of healthy individuals and individuals with the various pathologies are most likely due to the different levels of premortal hypoxia that the tissue had been exposed to. Moreover, widespread antigens used in practice were divided into 2 groups by their tolerance to autolysis: stable and unstable ones. This can be useful for the development of immunohistochemical test algorithms for the diagnostics on autopsy material.
Asunto(s)
Artefactos , Autólisis/patología , Cuerpo Carotídeo/ultraestructura , Paro Cardíaco/patología , Hipoxia/patología , Células Madre/ultraestructura , Animales , Autólisis/metabolismo , Autopsia/normas , Biomarcadores/metabolismo , Cuerpo Carotídeo/metabolismo , Cuerpo Carotídeo/patología , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Paro Cardíaco/genética , Paro Cardíaco/metabolismo , Humanos , Hipoxia/genética , Hipoxia/metabolismo , Inmunohistoquímica , Modelos Biológicos , Ratas , Ratas Wistar , Células Madre/metabolismo , Células Madre/patología , Sinaptofisina/genética , Sinaptofisina/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismoRESUMEN
Blood and cerebrospinal fluid (CSF) acidosis is the most troubling complication in subarachnoid hemorrhage (SAH) if carotid body (CB) networks are disrupted. However, histopathological examination of the choroid plexus (CP) in acidic CSF has not been evaluated so far. In this study, we aimed to investigate the CP in acidic CSF following SAH. Twenty-eight rabbits were used. Five rabbits were used to analyze CB network (control group; n = 5); seven rabbits were injected 1 mL of saline (Sham group; n = 7); and the rest 16 rabbits were given 1 mL of autologous arterial blood inject into the cisterna magna to create SAH (SAH group; n = 16). Blood and CSF pH values were recorded before/during/after the experimental procedures. Nuclear darkening, cellular shrinkage and pyknosis suggested the presence of apoptosis of epithelial cells of CP. The densities of normal and degenerated epithelial cells of CPs were estimated using stereological methods. The relationship between the pH values and degenerated epithelial cell densities of CPs were statistically compared by Mann-Whitney U-test. The pH values of blood were estimated as 7.359 ± 0.039 in the control group, 7.318 ± 0.062 in the Sham group, 7.23 ± 0.013 in the SAH group. CSF pH values were 7.313 ± 0.028 in the control group, 7.296 ± 0.045 in the Sham group, and 7.224 ± 0.012 in the SAH group. Degenerated epithelial cell density of CP was 25 ± 7 in the control group, 226 ± 64 in the Sham group, and 2115 ± 635 in the SAH group. There was a considerable link between CSF pH values and degenerated epithelial cells of CP (P < 0.0001). This study shows that CB insult causes acidosis of CSF as well as cellular degeneration of CP during SAH. This is the first description of this in the literature.
Asunto(s)
Acidosis/patología , Ventrículos Cerebrales/patología , Líquido Cefalorraquídeo/química , Plexo Coroideo/patología , Hemorragia Subaracnoidea/patología , Acidosis/etiología , Animales , Cuerpo Carotídeo/patología , Modelos Animales de Enfermedad , Concentración de Iones de Hidrógeno , Conejos , Hemorragia Subaracnoidea/complicacionesRESUMEN
Acidosis is the most dangerous complication of subarachnoid hemorrhage (SAH). Although the carotid bodies (CBs) network is essential for pH regulation, neither binuclear neurons (BNN) nor their functions have been mentioned so far in the literature. The aim of this study was to investigate the crucial roles of mononuclear (MNN) or BNN in CBs on acidosis following SAH. Twenty-five hybrid rabbits were used. Five rabbits were used as a control group, six for sham, and the remaining 14 rabbits were used as the study group by injection of 1 mL of autologous arterial blood into the cisterna magna to produce SAH. Normal and degenerated MNN/BNN densities of CBs were counted by stereological methods. The mean blood pH values were: 7.362 ± 0.041 in the control group; 7.324 ± 0.064 in sham, 7.272 ± 0.062 in the SAH group. The degenerated MNN and BNN values were 5 ± 1/mm3 and 9 ± 3/mm3 in the control group; 15 ± 5/mm3 and 22 ± 6/mm3 in sham, 965 ± 113/mm3 and 1532 ± 176/mm3 in the SAH group. Mean pH values were under 7.212 ± 0.130 in animals with prominent degenerated BNN. The differences between MNN/pH changes were significant between the SAH and control groups (P < 0.005); whereas BNN/pH values were significant between the SAH and sham groups (pH < 0.005), SAH and control (P < 0.0001). BNN degeneration could result in more severe acidosis than MNN following SAH which has not been described so far.
Asunto(s)
Acidosis/complicaciones , Cuerpo Carotídeo/metabolismo , Neuronas/metabolismo , Hemorragia Subaracnoidea/sangre , Animales , Cuerpo Carotídeo/patología , Concentración de Iones de Hidrógeno , Neuronas/patología , Conejos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/patologíaRESUMEN
Chronic exposure to intermittent hyperoxia causes abnormal carotid body development and attenuates the hypoxic ventilatory response (HVR) in neonatal rats. We hypothesized that concurrent exposure to intermittent hypercapnic hypoxia would influence this plasticity. Newborn rats were exposed to alternating bouts of hypercapnic hypoxia (10% O2/6% CO2) and hyperoxia (30-40% O2) (5 cycles h-1, 24 h d-1) through 13-14 days of age; the experiment was run twice, once in a background of 21% O2 and once in a background of 30% O2 (i.e., "relative hyperoxia"). Hyperoxia had only small effects on carotid body development when combined with intermittent hypercapnic hypoxia: the carotid chemoafferent response to hypoxia was reduced, but this did not affect the HVR. In contrast, sustained exposure to 30% O2 reduced carotid chemoafferent activity and carotid body size which resulted in a blunted HVR. When given alone, chronic intermittent hypercapnic hypoxia increased carotid body size and reduced the hypercapnic ventilatory response but did not affect the HVR. Overall, it appears that intermittent hypercapnic hypoxia counteracted the effects of hyperoxia on the carotid body and prevented developmental plasticity of the HVR.
Asunto(s)
Hipercapnia/fisiopatología , Hiperoxia/fisiopatología , Ventilación Pulmonar/fisiología , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Análisis de los Gases de la Sangre , Cuerpo Carotídeo/patología , Cuerpo Carotídeo/fisiopatología , Femenino , Hemoglobinas/metabolismo , Pulmón/patología , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Mecánica Respiratoria , Factores de TiempoRESUMEN
The role of cystathionine-γ-lyase (CSE) derived H2S in the hypoxic and anoxic responses of the carotid body (CB) were examined. Experiments were performed on Sprague-Dawley rats, wild type and CSE knockout mice on C57BL/6 J background. Hypoxia (pO2 = 37 ± 3 mmHg) increased the CB sensory nerve activity and elevated H2S levels in rats. In contrast, anoxia (pO2 = 5 ± 4 mmHg) produced only a modest CB sensory excitation with no change in H2S levels. DL-propargylglycine (DL-PAG), a blocker of CSE, inhibited hypoxia but not anoxia-evoked CB sensory excitation and [Ca2+]i elevation of glomus cells. The inhibitory effects of DL-PAG on hypoxia were seen: a) when it is dissolved in saline but not in dimethyl sulfoxide (DMSO), and b) in glomus cells cultured for18 h but not in cells either soon after isolation or after prolonged culturing (72 h) requiring 1-3 h of incubation. On the other hand, anoxia-induced [Ca2+]i responses of glomus cell were blocked by high concentration of DL-PAG (300µM) either alone or in combination with aminooxyacetic acid (AOAA; 300µM) with a decreased cell viability. Anoxia produced a weak CB sensory excitation and robust [Ca2+]i elevation in glomus cells of both wild-type and CSE null mice. As compared to wild-type, CSE null mice exhibited impaired CB chemo reflex as evidenced by attenuated efferent phrenic nerve responses to brief hyperoxia (Dejours test), and hypoxia. Inhalation of 100% N2 (anoxia) depressed breathing in both CSE null and wild-type mice. These observations demonstrate that a) hypoxia and anoxia are not analogous stimuli for studying CB physiology and b) CSE-derived H2S contributes to CB response to hypoxia but not to that of anoxia.
Asunto(s)
Cuerpo Carotídeo/efectos de los fármacos , Cistationina gamma-Liasa/metabolismo , Hipoxia/patología , Sulfitos/uso terapéutico , Potenciales de Acción/efectos de los fármacos , Animales , Calcio/metabolismo , Cuerpo Carotídeo/patología , Células Cultivadas , Cistationina gamma-Liasa/genética , Hipoxia/tratamiento farmacológico , Masculino , Nervio Frénico/efectos de los fármacos , Nervio Frénico/fisiología , Ratas , Ratas Sprague-Dawley , Sulfitos/farmacologíaRESUMEN
BACKGROUND: The use of long-term immunosuppressive treatments on neural transplantation has been controversial during the last decades. Although nowadays there is a consensus about the necessity of maintaining a permanent state of immunosuppression to preserve the survival of cerebral grafts, little is known about the effects that chronic immunosuppression produces both on the neurodegenerative process and on transplants function. METHODS: Here, we establish a new immunosuppressive protocol, based on the discontinuous administration of CsA (15 mg/kg; s.c.) and prednisone (20 mg/kg; s.c.), to produce long-term immunosuppression in mice. Using this treatment, we analyse the effects that long-term immunosuppression induces in a chronic 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) model of parkinsonism and on the neuroprotective and neurorestorative anti-parkinsonian actions exerted by rat carotid body (CB) xenografts. RESULTS: This protocol preserves the survival of rat CB xenotransplants maintaining the general wellness of the grafted mice. Although permanent immunosuppression does not prevent the MPTP-induced cell death of nigral neurons and the consequent degeneration of dopaminergic striatal innervation, allowing for its use as Parkinson's disease (PD) model, it reduces the microglial activation and slightly declines the striatal damage. Moreover, we reported that chronic administration of immunosuppressant drugs does not alter the neuroprotective and restorative anti-parkinsonian actions of rat CB xenografts into parkinsonian mice. CONCLUSIONS: This new immunosuppressive protocol provides a new murine model to assay the long-term effects of cerebral xenografts and offer a pharmacological alternative to the commonly used genetic immunodeficient mice, allowing the use of genetically modified mice as hosts. In addition, it will permit the experimental analysis of the effects produced by human CB xenografts in the chronic PD murine model, with the final aim of using CB allografts as an option of cell therapy in PD patients.
Asunto(s)
Cuerpo Carotídeo/patología , Tratamiento Basado en Trasplante de Células y Tejidos , Xenoinjertos/efectos de los fármacos , Terapia de Inmunosupresión , Trasplante Heterólogo , Animales , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Dopamina/metabolismo , Terapia de Inmunosupresión/métodos , Masculino , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/patologíaRESUMEN
Chronic intermittent hypoxia (CIH), main feature of obstructive sleep apnea, produces nitro-oxidative stress, which contributes to potentiate carotid body (CB) chemosensory discharges and sympathetic-adrenal-axis activity, leading to hypertension. The MnSOD enzymatic activity, a key enzyme on oxidative stress control, is reduced by superoxide-induced nitration. However, the effects of CIH-induced nitration on MnSOD enzymatic activity in the CB and adrenal gland are not known. We studied the effects of CIH on MnSOD protein and immunoreactive (MnSOD-ir) levels in the CB, adrenal gland and superior cervical ganglion (SCG), and on 3-nitrotyrosine (3-NT-ir), CuZnSOD (CuZnSOD-ir), MnSOD nitration, and its enzymatic activity in the CB and adrenal gland from male Sprague-Dawley rats exposed to CIH for 7 days. CIH increased 3-NT-ir in CB and adrenal gland, whereas MnSOD-ir increased in the CB and in adrenal cortex, but not in the whole adrenal medulla or SCG. CIH nitrated MnSOD in the CB and adrenal medulla, but its activity decreased in the adrenal gland. CuZnSOD-ir remained unchanged in both tissues. All changes observed were prevented by ascorbic acid treatment. Present results show that CIH for 7 days produced MnSOD nitration, but failed to reduce its activity in the CB, because of the increased protein level.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Cuerpo Carotídeo/metabolismo , Hipoxia/metabolismo , Superóxido Dismutasa/metabolismo , Tirosina/análogos & derivados , Glándulas Suprarrenales/patología , Animales , Cuerpo Carotídeo/patología , Hipoxia/patología , Inmunohistoquímica , Masculino , Estrés Nitrosativo , Estrés Oxidativo , Ratas Sprague-Dawley , Tirosina/análisis , Tirosina/metabolismoRESUMEN
It has recently been established that carotid bodies play a significant role in the regulation of activities of the cardiovascular system as well as in the pathogenesis of arterial hypertension, heart failure and diabetes. Aim of study was to determinate the influence of polymorphisms within genes of the renin-angiotensin-aldosterone system (RAAS) on the volume of the carotid bodies (CB) in patients with hypertension (HTA). The study group consisted of 77 patients with HTA. All patients were genotyped for single-nucleotide polymorphisms of genes coding for: angiotensinogen: rs4762, rs5049, rs5051 and rs699; angiotensin-converting enzyme: rs4343; angiotensin receptor type 1 gene (AGTR1): rs5182 and rs5186; and the aldosterone synthase: rs1799998. The estimation of volumes of CB (VrCB+lCB) was based on computed tomography angiography. Among individuals with essential hypertension certain relationships were documented between rs5182 and rs5186 polymorphisms of AGTR1 gene and rs1799998 polymorphism of CYP11B2 gene on one hand and the volume of carotid bodies on one other. Patients carrying the C alleles within the rs5182 and rs5186 of AGTR1 gene was associated with higher values of VrCB+lCB. The carriage of the T allele in the rs5182 locus of the AGTR1 gene determine lower values of VrCB+lCB. In summary, in patients with HTA a higher volume of CB may be resulted from the presence of specific genotypes in RAAS.
Asunto(s)
Cuerpo Carotídeo/diagnóstico por imagen , Citocromo P-450 CYP11B2/genética , Hipertensión Esencial/diagnóstico por imagen , Hipertensión Esencial/genética , Polimorfismo de Nucleótido Simple , Receptor de Angiotensina Tipo 1/genética , Anciano , Cuerpo Carotídeo/patología , Angiografía por Tomografía Computarizada , Hipertensión Esencial/tratamiento farmacológico , Femenino , Estudios de Asociación Genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Humanos , Masculino , Tamaño de los Órganos , Estudios RetrospectivosRESUMEN
Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H2S production in the CB. Blockade of H2S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H2S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H2S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H2S. Inhibiting H2S synthesis prevented IH-evoked sympathetic activation and hypertension.
Asunto(s)
Cuerpo Carotídeo/metabolismo , Cuerpo Carotídeo/patología , Gases/metabolismo , Hipoxia/metabolismo , Hipoxia/patología , Especies Reactivas de Oxígeno/metabolismo , Animales , Humanos , Sulfuro de Hidrógeno/metabolismoRESUMEN
The carotid body is now looked at as a multipurpose sensor for blood gases, blood pH, and several hormones. The matter of glucose sensing by the carotid body has been debated for several years in the literature, and these days there is a consensus that carotid body activity is modified by metabolic factors that contribute to glucose homeostasis. However, the sensing ability for glucose is still being pondered: are the carotid bodies low glucose sensors or, in contrast, are they overresponsive in high-glucose conditions? Herein, we debate the glucose and insulin sensing capabilities of the carotid body as key early events in the overactivation of the carotid body, which is increasingly recognized as an important feature of metabolic diseases. Additionally, we dedicate a final section to discuss new outside-the-box therapies designed to decrease carotid body activity that may be used for treating metabolic diseases.
Asunto(s)
Cuerpo Carotídeo/metabolismo , Cuerpo Carotídeo/patología , Resistencia a la Insulina , Animales , Humanos , Enfermedades Metabólicas/patología , Sistema Nervioso Simpático/patologíaRESUMEN
Introducción: Los tumores del cuerpo carotideo son tumores infrecuentes, generalmente benignos y muy vascularizados, por lo que su resección es un reto para el cirujano. El objetivo de este estudio es realizar una caracterización epidemiológica de los pacientes con glomus carotideo operados en la Unidad de Cirugía Cardiovascular de Guatemala (UNICAR) Metodología: El estudio fue descriptvo retrospectivo analizando los registros clínicos de todos los pacientes sometidos a resección de glomus carotideo en UNICAR de enero de 2,002 a diciembre de 2,015. Resultados: Se documentaron 17 pacientes a quienes se les realizo resección de glomus en la unidad, de los cuales 1 expediente no fue posible analizar porque no se encontró en el archivo. El 93% de los pacientes fueron de sexo femenino lo cual está descrito que es el género más afectado. La altitud es característica de esta patología ya que el 93%, 15 de los 16 venían de una altura mayor de los 1,500 mts sobre el nivel del mar. No se pudo determinar la etnia como factor de riesgo ya que el 50% de los pacientes fueron de etnia indígena y el 50% de etnia ladina. Se obtuvo un caso de herencia familiar ya que tanto la abuela como la nieta presentaron glomus carotideo. Las biopsias que se documentaron fueron solamente en 5 pero pensamos que hay un subregistro ya que consultando con los especialistas estás pudieron haber sido más. Conclusiones: El Glomus Carotideo es una patología poco frecuente, sin embargo, debe ser tratado en unidades especializadas vasculares debido a su compleja resección y el importante riesgo de sangrado. En este estudio se logró caracterizar epidemiológicamente a los pacientes, coincidiendo con lo reportado en la literatura mundial.
Background: Carotid body tumors are uncommon, generally benign, hypervascular turmors; resection is a challenge for surgeons. The aim of this study is to characterize patents with carotid body tumors who underwent resection at the Cardiovascular Surgical Unit in Guatemala (UNICAR) Methods and Results: There were a total of 17 patents in this descriptve and retrospectve trial who underwent resection of carotid body tumor during 2002 to 2015, but we only had access to 16 of the patents clinical records. 93% were female patents, this is the same as reported in other trials being women more affected than men. Altitude of more than 1,500 m from sea level was present in 93% of the patents. This is remarkable due to the country's geography where there can be in some department's altitudes from 0 m at sea level to as high as 2,800 m. Their background in race speaking isn't related to the presence of this pathology, 50% were indigenous and 50% were ladinos. There was only one case of family related heritage where grandmother and granddaughter had a carotid body tumor resection. Previous biopsy was only recorded in 5 clinical records but we think this can be a sub registry due to the experience of some of the surgeons who said most of them had previous scars and it made the resection more difficult. Conclusions: Carotid body tumors are rare in presentation and they must be treated in a specialized vascular unit due to its complex resection and hemorrhage risk.
Asunto(s)
Humanos , Masculino , Femenino , Tumor del Cuerpo Carotídeo/cirugía , Cuerpo Carotídeo/patología , Estudios Epidemiológicos , Paraganglios CromafinesRESUMEN
Cystathionine-γ-lyase (CSE) is a multifunctional enzyme, and hydrogen sulfide (H2S) is one of its products. CSE and H2S have recently been proposed to be critical signaling molecules in hypoxia-induced excitation of carotid body (CB) glomus cells and the chemosensory response. Because the role of H2S in arterial chemoreception is still debated, we further examined the role of CSE by studying the effects of hypoxia on TASK K+ channel activity, cell depolarization, [Ca2+]i and ventilation using CSE+/+ and CSE-/- mice. As predicted, hypoxia reduced TASK activity and depolarized glomus cells isolated from CSE+/+ mice. These effects of hypoxia were not significantly altered in glomus cells from CSE-/- mice. Basal [Ca2+]i and hypoxia-induced elevation of [Ca2+] were also not significantly different in glomus cells from CSE+/+ and CSE-/- mice. In whole-body plethysmography, hypoxia (10%O2) increased minute ventilation in both CSE+/+ and CSE-/- mice equally well, and no significant differences were found in either males or females when adjusted by body weight. Together, these results show that deletion of the CSE gene has no effects on hypoxia-induced changes in TASK, cell depolarization, [Ca2+]i and ventilation, and therefore do not support the idea that CSE/H2S signaling is important for CB chemoreceptor activity in mice.
Asunto(s)
Calcio/metabolismo , Cuerpo Carotídeo/patología , Cistationina gamma-Liasa/metabolismo , Hipoxia , Proteínas del Tejido Nervioso/metabolismo , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Ventilación , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Animales , Animales Modificados Genéticamente , Bicarbonatos/farmacología , Células Quimiorreceptoras/efectos de los fármacos , Células Quimiorreceptoras/fisiología , Cistationina gamma-Liasa/genética , Modelos Animales de Enfermedad , Femenino , Sulfuro de Hidrógeno/metabolismo , Hipoxia/metabolismo , Hipoxia/patología , Hipoxia/terapia , Masculino , Ratones , Ratones Endogámicos C57BL , Oxígeno/farmacología , Cloruro de Potasio/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Volumen de Ventilación Pulmonar/efectos de los fármacos , Volumen de Ventilación Pulmonar/fisiologíaRESUMEN
The purpose of this study was to investigate immunoreactivity for dopamine ß-hydroxylase (DBH) and tyrosine hydroxylase (TH) in carotid body (CB) glomus cells in spontaneously hypertensive rats (SHR/Izm) at 4 (prehypertensive stage), 8 (early stage of developmental hypertension), 12 (later stage of developmental hypertension), and 16weeks of age (established hypertensive stage). Age-matched Wistar Kyoto rats (WKY/Izm) were used as controls. Staining properties for TH were similar between both strains at each age. Regarding DBH immunostaining, although some glomus cells showed intense DBH immunoreactivity at 4weeks of age, these cells were rarely observed at 8, 12, and 16weeks of age in WKY/Izm. In SHR/Izm, intense DBH immunoreactivity was observed in some glomus cells at 4weeks of age, these cells were also observed at 8 and 12weeks of age, and their number increased at 16weeks of age. An image analysis showed that the percentage of DBH-immunopositive glomus cells in WKY/Izm was approximately 30% at 4weeks of age and significantly decreased to approximately 10% at 8, 12, and 16weeks of age (p<0.05). This percentage in SHR/Izm was approximately 40% at each age. The gray scale intensity for DBH immunoreactivity in DBH-immunopositive glomus cells was similar in both strains at 4weeks of age, but became significantly lower in WKY/Izm and higher in SHR/Izm with increase in age (p<0.05). These results suggest that noradrenaline in glomus cells plays an important role in the regulation of neurotransmission between CB and afferent nerves during developmental hypertension.
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Envejecimiento/metabolismo , Cuerpo Carotídeo/enzimología , Dopamina beta-Hidroxilasa/metabolismo , Hipertensión/enzimología , Envejecimiento/patología , Animales , Cuerpo Carotídeo/crecimiento & desarrollo , Cuerpo Carotídeo/patología , Recuento de Células , Técnica del Anticuerpo Fluorescente , Hipertensión/patología , Masculino , Neuronas/enzimología , Neuronas/patología , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
OBJECTIVE: The chemoreceptor network, consisting of the glossopharyngeal nerve and carotid body (GPN-CB), is essential for the regulation of blood pH. Its ischemic insults after subarachnoid hemorrhage (SAH), which may contribute to acidosis, have not been investigated. METHODS: Twenty-three hybrid rabbits were used. They were divided into 3 groups: 5 as a control group, 5 as a sham group, and the remaining 13 as the study group. Injections included 1 cm3 serum saline and 1 cm3 autolog arterial blood into the cisterna magna in the sham and study group, respectively. Blood pH values of all animals were recorded. After 2 weeks, animals were euthanized. The number of normal and degenerated neurons of the carotid bodies (CBs) was counted by stereologic methods and analyzed statistically. RESULTS: Two of 13 rabbits died within the second week. The mean blood pH values were measured as 7.35 ± 0.07 in the control group (n = 5), 7.33 ± 0.06 in the sham group (n = 5), 7.29 ± 0.05 in rabbits with slight acidosis (n = 6), and 7.23 ± 0.02 in rabbits with prominent acidosis (n = 7). In the control group, the average normal neuronal density of the CBs was 6432 ± 790/mm3 and the degenerated neuron density was 11 ± 3/mm3, whereas the degenerated neuronal density in CBs was 35 ± 8/mm3 in the sham group and 1034 ± 112/mm3 in the slight acidosis-developed group (n = 6; P < 0.05). Conversely, degenerated neuron density of CBs was 2134 ± 251/mm3 in the prominent acidosis-developed animals (n = 7; P < 0.005). Interestingly, in the rabbits who died, the degenerated neuron density of the CB was 3160 ± 840/mm3. CONCLUSION: An inverse relationship between neurodegeneration in the CB and pH values secondary to the disruption of the GPN-CB network after SAH was found, which may contribute to developing acidosis.
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Acidosis/fisiopatología , Análisis Químico de la Sangre , Cuerpo Carotídeo/fisiopatología , Modelos Animales de Enfermedad , Nervio Glosofaríngeo/fisiopatología , Red Nerviosa/fisiopatología , Hemorragia Subaracnoidea/fisiopatología , Resultado del Tratamiento , Acidosis/patología , Animales , Cuerpo Carotídeo/patología , Nervio Glosofaríngeo/patología , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Red Nerviosa/patología , Conejos , Hemorragia Subaracnoidea/patologíaAsunto(s)
Hipoxia , Oxígeno/metabolismo , Apnea Obstructiva del Sueño , Animales , Cuerpo Carotídeo/metabolismo , Cuerpo Carotídeo/patología , Cuerpo Carotídeo/fisiopatología , Enfermedad Crónica , Humanos , Hipoxia/metabolismo , Hipoxia/patología , Hipoxia/fisiopatología , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/patología , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
Background The study aims to conduct a review of the surgical management of carotid body tumor. Methods Consecutive patients with CBT who received surgical interventions from January 1994 to January 2014 at our institution were reviewed. Clinical, operative, pathological and follow up information were reported. Results Twenty patients (four males; median age was 36) with 21 CBT operations were recorded during the period. One patient undertook sequential operations for bilateral CBTs. Patients had 19 neck mass, 1 incidental finding and 1 facial nerve palsy. Six CBTs (28.6%) were Shamblin class I, ten (47.6%) were class II and five (23.8%) were class III. Nine CBTs had preoperative conjunctive embolization. Two operations required internal carotid artery resection and reconstruction. Four patients received subtotal resections, while 17 achieved complete resection. Complications included two major strokes, three hoarse voice and two Horner's syndrome. Shamblin class was significant predictor of operative time, blood loss, and whether complete resection accomplished, but could not predict postoperative complication. With median follow up period of 94 months, there was no tumor recurrence found in those had complete resection. Conclusions This small cohort showed that Shamblin class was significant in predicting technical difficulties but could not predict occurrence of complications.