RESUMEN
Upper urinary tract urolithiasis is an emerging disease in cats, with 98% of kidney stones composed of calcium oxalate. In humans, disturbances in the intestinal and urinary microbiota are suspected to contribute to the formation of calcium oxalate stones. We hypothesized that similar mechanisms may be at play in cats. This study examines the intestinal and urinary microbiota of nine cats with kidney stones compared to nine healthy cats before, during, and after treatment with the antibiotic cefovecin, a cephalosporin. Initially, cats with kidney stones displayed a less diverse intestinal microbiota. Antibiotic treatment reduced microbiota diversity in both groups. The absence of specific intestinal bacteria could lead to a loss of the functions these bacteria perform, such as oxalate degradation, which may contribute to the formation of calcium oxalate stones. This study confirms the presence of a distinct urobiome in cats with kidney stones, characterized by greater richness and diversity compared to healthy cats. These findings highlight the potential of microbiota modulation as a strategy to prevent renal lithiasis in cats.
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An 18-month-old neutered male domestic shorthair cat was presented for an emergency consultation after falling from the second floor. The cat sustained minor traumatic injuries but did not exhibit dyspnea. Routine radiographic examination raised suspicion of a diaphragmatic hernia, but the circumscribed nature of the soft tissues visible in the thorax was atypical for a classic traumatic diaphragmatic hernia. A positive contrast peritoneography highlighted the likely presence of a hernial sac, which strongly suggested a "true diaphragmatic hernia", also known as "pleuroperitoneal hernia". This diagnosis was confirmed during laparotomy, which allowed for the visualization of a 3 cm radial diaphragmatic defect in the right ventral quadrant of the pars sternalis. The diaphragm's edges were rounded. A portion of the falciform ligament and a part of the omentum were protruding through the defect and were contained within a hernial sac. Herniorrhaphy was performed. The cat recovered without complications. Given its presentation and location, ventrally and to the right, this anomaly is analogous to what is described in humans as "Morgagni hernia". Six other cases of Morgagni hernias have probably been reported in cats but were not identified as such. This case underscores the utility of peritoneography, a straightforward technique useful for diagnosing diaphragmatic hernias, which enables differentiation between acquired traumatic forms and congenital forms, particularly peritoneopericardial hernias and pleuroperitoneal hernias. True diaphragmatic hernias are almost always serendipitous discoveries.
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Restless legs syndrome (RLS) is a common chronic sensory-motor neurological disorder that remains a clinical diagnosis. Most RLS patients present with sleep complaints in the form of initiation and/or maintenance insomnia as RLS has a circadian rhythmicity. An increased number of periodic leg movements during sleep (PLMS) is a supportive criterion in the diagnosis of RLS. Abnormalities in the central dopaminergic and iron systems are involved in the physiopathology of RLS. There is a higher prevalence of RLS and PLMS in sleep-disordered breathing patients, particularly those with obstructive sleep apnoea (OSA), the most common sleep disorder in western societies. The complex mechanisms underlying the association between OSA, RLS and PLMS remain unclear. Untreated OSA can lead to adverse cardiovascular consequences due to cardio-metabolic dysfunction. It remains controversial whether RLS could further adversely impact the cardiovascular consequences of OSA. The PLMS do not have an additive effect on the hypersomnia experienced by some sleep-disordered breathing patients. Continuous positive airway pressure (CPAP) therapy is the most effective therapy for OSA. The presence of PLMS during CPAP treatment could be a marker of an incomplete resolution of sleep-disordered breathing in the form of increased upper airway resistance syndrome, despite treatment. Dopaminergic agonists are the preferred agent for the treatment of RLS, and are indicated when RLS symptoms are frequent and affect quality of life. PLMS and RLS do not seem to contribute to the residual hypersomnia that can be observed in some sleep-disordered breathing patients despite adequate compliance and effective CPAP therapy.
Asunto(s)
Síndrome de las Piernas Inquietas/epidemiología , Síndrome de las Piernas Inquietas/fisiopatología , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/fisiopatología , Comorbilidad , Presión de las Vías Aéreas Positiva Contínua , Humanos , Síndrome de Mioclonía Nocturna/epidemiología , Síndrome de Mioclonía Nocturna/fisiopatología , Prevalencia , Síndrome de las Piernas Inquietas/clasificación , Síndromes de la Apnea del Sueño/terapia , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/terapia , Resultado del TratamientoRESUMEN
Recent trials in patients with neurodegenerative diseases documented the safety of gene therapy based on adeno-associated virus (AAV) vectors deposited into the brain. Inborn errors of the metabolism are the most frequent causes of neurodegeneration in pre-adulthood. In Sanfilippo syndrome, a lysosomal storage disease in which heparan sulfate oligosaccharides accumulate, the onset of clinical manifestation is before 5 years. Studies in the mouse model showed that gene therapy providing the missing enzyme α-N-acetyl-glucosaminidase to brain cells prevents neurodegeneration and improves behavior. We now document safety and efficacy in affected dogs. Animals received eight deposits of a serotype 5 AAV vector, including vector prepared in insect Sf9 cells. As shown previously in dogs with the closely related Hurler syndrome, immunosuppression was necessary to prevent neuroinflammation and elimination of transduced cells. In immunosuppressed dogs, vector was efficiently delivered throughout the brain, induced α-N-acetyl-glucosaminidase production, cleared stored compounds and storage lesions. The suitability of the procedure for clinical application was further assessed in Hurler dogs, providing information on reproducibility, tolerance, appropriate vector type and dosage, and optimal age for treatment in a total number of 25 treated dogs. Results strongly support projects of human trials aimed at assessing this treatment in Sanfilippo syndrome.
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Encéfalo/metabolismo , Terapia Genética/métodos , Mucopolisacaridosis III/terapia , Mucopolisacaridosis I/terapia , Acetilglucosaminidasa/genética , Animales , Encéfalo/patología , Dependovirus/genética , Modelos Animales de Enfermedad , Perros , Terapia Genética/efectos adversos , Vectores Genéticos/genética , Reacción en Cadena de la PolimerasaRESUMEN
UNLABELLED: CASE HISTORY AND PRESENTATION: Two non-human primates (Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 µg hour(-1) transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. MANAGEMENT AND FOLLOW-UP: Attempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 µg L(-1) ) confirmed fentanyl overdose. CONCLUSIONS: This report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach.
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Sobredosis de Droga/patología , Fentanilo/envenenamiento , Macaca fascicularis , Administración Cutánea , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/envenenamiento , Animales , Masculino , Naloxona/administración & dosificación , Naloxona/farmacología , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/farmacologíaRESUMEN
Despite the ability to determine feline blood types, the transfusion of canine blood to cats is still practiced in some countries. Xenotransfusion is effective-even if its effects only last for a few days-and is not associated with serious adverse effects. It avoids the need for blood typing, and most importantly, it avoids the transmission of intraspecific infectious agents, notably the feline leukemia virus (FeLV). Transfusion with canine blood is easier, quicker and less costly than transfusion with feline blood; it is less disagreeable for the donor. In the light of these arguments, when feline blood collected according to current guidelines is not available, in particular when the donor is not confirmed to be negative for the FeLV provirus, the authors consider it to be judicious to use canine blood for feline transfusion in emergency situations; this practice is preferable to inaction and to the inoculation of an infectious agent. Allotransfusion remains preferable in non-emergency situations as a treatment of chronic compensated anaemiae or if an appropriate donor (negative for FeLV provirus) is available. However, 2-4 days after a xenotransfusion, if a clinical alteration and a significant decrease in haematocrit are observed, a transfusion with cat's blood confirmed to be negative for FeLV provirus should be performed. Xenotransfusion should never be used twice.
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A 5-year-old recently castrated male Doberman dog presented for prolonged erection of one week's duration with associated pain and dysuria. This was the fourth episode within a year. Each episode was associated with an unusual event, which was stressful for the dog. Castration performed two months prior to the final episode did not prevent recurrence. Due to tissue necrosis, penile amputation and urethrostomy had to be performed. The dog recovered fully. Prolonged erection that persists beyond or that is unrelated to sexual stimulation is called "priapism". This term refers to the Greek god Priapus, a god of fertility, memorialized in sculptures for his giant phallus. In humans, depending on the mechanism involved, priapism is classified as nonischemic or ischemic. Because prognosis and treatment are different, priapism must be determined to be nonischemic or ischemic. Nonischemic priapism is a rare condition observed when an increase in penile arterial blood flow overwhelms the capacity of venous drainage; it is often associated with penile trauma, and does not require medical intervention. Ischemic priapism is associated with decreased venous return. In humans, ischemic priapism accounts for 95% of cases, the majority of which are idiopathic. Ischemic priapism is a urological emergency; simple conservative measures such as aspiration of blood from the corpora cavernosa and intracavernosal injection of an adrenergic agent are often successful. Stuttering priapism, also called recurrent or intermittent priapism, is a particular form of ischemic priapism reported in humans that is characterized by repetitive episodes of prolonged erections. Management consists of treating each new episode as an episode of acute ischemic priapism, and preventing recurrence with oral medications such as dutasteride and/or baclofen, gabapentin, or tadalafil. To the authors' knowledge, this case is the first report of stuttering priapism in a dog.
RESUMEN
A 6-year-old mixed-breed male Papillon dog, castrated at the age of 7 months, presented for work-up of a difficulty walking associated with constipation and urinary incontinence. Ultrasonography and radiography were consistent with a tumor of the prostate and lymph node metastases. An irregular osteoproliferation of the ventral edges of L5-L6-L7 suggested tumor invasion. Periosteal proliferative lesions of the pelvis, the femur, the humerus, the tibia and the calcaneus were consistent with hypertrophic osteopathy. Necropsy and histological examination confirmed the diagnosis of prostatic adenocarcinoma with lymph node, pulmonary, liver and bone metastases, associated with hypertrophic osteopathy.
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BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) patients are at risk of recurrent vascular events. The primary objectives were to evaluate among TIA patients the prevalence of sleep apnea and among patients with sleep apnea auto-titrating continuous positive airway pressure (auto-CPAP) adherence. The secondary objective was to describe among TIA patients with sleep apnea the recurrent vascular event rate by auto-CPAP use category. METHODS: All intervention patients received auto-CPAP for 2 nights, but only intervention patients with evidence of sleep apnea received auto-CPAP for the remainder of the 90-day period. Intervention patients received polysomnography at 90 days after TIA. Control patients received polysomnography at baseline and at 90 days. Acceptable auto-CPAP adherence was defined as >or=4 hours per night for >or=75% of nights. Vascular events included recurrent TIA, stroke, hospitalization for congestive heart failure, myocardial infarction, or death. RESULTS: We enrolled 70 acute TIA patients: 45 intervention and 25 control. The majority of patients had sleep apnea: 57% at baseline and 59% at 90 days. Among the 30 intervention patients with airflow obstruction, 12 (40%) had acceptable auto-CPAP adherence, 18 (60%) had some use, and none had no use. Three intervention patients (12%) had recurrent events compared with 1 (2%; P=0.13) control patient. The vascular event rate was highest among sleep apnea patients with no CPAP use: none, 16%; some, 5%; acceptable adherence 0% (P=0.08). CONCLUSIONS: Sleep apnea is common among acute TIA patients. It appears feasible to provide auto-CPAP in the acute TIA period. Larger studies should evaluate whether a strategy of diagnosing and treating sleep apnea can reduce recurrent vascular events after TIA.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua/instrumentación , Ataque Isquémico Transitorio/terapia , Síndromes de la Apnea del Sueño/terapia , Anciano , Anciano de 80 o más Años , Presión de las Vías Aéreas Positiva Contínua/métodos , Estudios de Factibilidad , Femenino , Humanos , Ataque Isquémico Transitorio/complicaciones , Masculino , Persona de Mediana Edad , Procesamiento de Señales Asistido por Computador/instrumentación , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/etiologíaRESUMEN
Sponges can be inadvertently left behind during surgery. A retained surgical sponge is called a textiloma, gossypiboma, or gauzoma. This complication is rare and rarely reported. These foreign bodies can lead to postoperative infection or abscess formation, while others remain asymptomatic for many years before leading to a granuloma with adhesions. This paper reports a case of extravesical textiloma in a spayed female dog with severe hematuria and a thickened bladder wall, mimicking a tumor on ultrasound. Clinical signs occurred >8 years after sterilization.
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Enfermedades de los Perros/etiología , Cuerpos Extraños/veterinaria , Granuloma/veterinaria , Hematuria/veterinaria , Complicaciones Posoperatorias/veterinaria , Tapones Quirúrgicos de Gaza/veterinaria , Animales , Diagnóstico Diferencial , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía , Perros , Femenino , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/etiología , Granuloma/etiología , Granuloma/cirugía , Hematuria/etiología , Ovariectomía/efectos adversos , Ovariectomía/veterinaria , Complicaciones Posoperatorias/etiología , Tapones Quirúrgicos de Gaza/efectos adversos , Resultado del Tratamiento , Ultrasonografía , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/veterinariaRESUMEN
Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk factors. Although patients with OSA have higher prevalence of hypertension and evidence of hypercoagulability, the mechanism of this increased risk is unknown. Obstructive apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow. These perturbations can adversely affect the cerebral circulation. We hypothesized that patients with OSA have impaired cerebral autoregulation, which may contribute to the increased risk of cerebral ischemia and stroke. We examined cerebral autoregulation in patients with and without OSA by measuring cerebral artery blood flow velocity (CBFV) by using transcranial Doppler ultrasound and arterial blood pressure using finger pulse photoplethysmography during orthostatic hypotension and recovery as well as during 5% CO(2) inhalation. Cerebral vascular conductance and reactivity were determined. Forty-eight subjects, 26 controls (age 41.0+/-2.3 yr) and 22 OSA (age 46.8+/-2.3 yr) free of cerebrovascular and active coronary artery disease participated in this study. OSA patients had a mean apnea-hypopnea index of 78.4+/-7.1 vs. 1.8+/-0.3 events/h in controls. The oxygen saturation during sleep was significantly lower in the OSA group (78+/-2%) vs. 91+/-1% in controls. The dynamic vascular analysis showed mean CBFV was significantly lower in OSA patients compared with controls (48+/-3 vs. 55+/-2 cm/s; P <0.05, respectively). The OSA group had a lower rate of recovery of cerebrovascular conductance for a given drop in blood pressure compared with controls (0.06+/-0.02 vs. 0.20+/-0.06 cm.s(-2).mmHg(-1); P <0.05). There was no difference in cerebrovascular vasodilatation in response to CO(2). The findings showed that patients with OSA have decreased CBFV at baseline and delayed cerebrovascular compensatory response to changes in blood pressure but not to CO(2). These perturbations may increase the risk of cerebral ischemia during obstructive apnea.
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Circulación Cerebrovascular/fisiología , Homeostasis/fisiología , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Presión Sanguínea/fisiología , Interpretación Estadística de Datos , Femenino , Humanos , Hipercapnia/fisiopatología , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , PolisomnografíaRESUMEN
The objectives of this study were (1) to evaluate the indications, complications and outcomes of multiple red cell transfusions (MrcTs) in cats; of these cats (2) to describe those that received massive transfusion and (3) compare them with those who received MrcTs over a longer time course. Twenty-seven cats were identified which received a total of 110 transfusions, with a median of three transfusions (range 3-15) per cat. The transfusions consisted of 47 units of whole blood and 63 units of packed red blood cells. The median age of cats was 6 years (range 6 months to 15 years). Cats were hospitalized for a median of 6 days, with a range of 1-38 days. No acute transfusion reactions were documented, although due to the critical nature of the cats, they may not have been appreciated. Sixteen cats survived to discharge and 11 died or were euthanased. Indications (and % survival) for transfusions included bone marrow failure (n=8; 50%); surgical loss (n=4; 100%), sepsis (n=3; 0%), neoplasia (n=3; 33%), acute renal failure (n=3; 66%), trauma (n=2; 100%), gastrointestinal bleeding (n=1; 100%), and cats with multiple disease processes (n=3; 33%). MrcTs are well-tolerated in cats and may be associated with a favorable outcome.
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Enfermedades de los Gatos/mortalidad , Enfermedades de los Gatos/terapia , Transfusión de Eritrocitos/veterinaria , Animales , Tipificación y Pruebas Cruzadas Sanguíneas/veterinaria , Enfermedades de la Médula Ósea/veterinaria , Gatos , Transfusión de Eritrocitos/efectos adversos , Femenino , Hemorragia Gastrointestinal/veterinaria , Masculino , Insuficiencia Renal/veterinaria , Sepsis/veterinaria , Resultado del TratamientoRESUMEN
This case report presents a 14-month-old female Poodle mix with acute megakaryoblastic leukemia based on a marked thrombocytosis, abnormal platelet morphology, circulating dwarf megakaryocytes, and blast cells in the blood. Bone marrow abnormalities included dysmegakaryopoiesis dygranulopoiesis, and an increased number of blast cells was observed in the blood. Extensive leukemic involvement was also found in the liver, spleen, lymph nodes, lungs, kidneys, and brain. The cytopathologic features of the abnormal circulating cells were highly suggestive of being megakaryocytic in origin, which was supported by negative myeloperoxidase staining and positive von Willebrand factor staining on immunocytochemistry (ICC). The neoplastic cells were also CD61 positive and had variable von Willebrand factor expression on ICC. Although there were only 25% blast cells in the bone marrow, which theoretically supported myelodysplastic syndrome, the hypothesis that this case represented acute myeloid leukemia of megakaryoblastic origin was confirmed by the continuous increase in circulating blast cell numbers during follow-up visits and the extensive leukemic involvement of parenchymal organs.
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Encéfalo/patología , Enfermedades de los Perros/patología , Leucemia Megacarioblástica Aguda/veterinaria , Trombocitosis/veterinaria , Animales , Perros , Femenino , Leucemia Megacarioblástica Aguda/complicaciones , Leucemia Megacarioblástica Aguda/patología , Trombocitosis/etiologíaRESUMEN
An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume mechanical ventilation in an elastase-induced murine model of pulmonary emphysema. In this model, two time points, associated with different levels of lung inflammation but similar lung destruction, were analyzed. C57BL/6 mice received a tracheal instillation of 5 IU of porcine pancreatic elastase (Elastase mice) or the same volume of saline (Saline mice). Fourteen (D14) and 21 (D21) days after instillation, mice were anesthetized, intubated, and either mechanically ventilated (MV) or maintained on spontaneous ventilation (SV) during two hours. As compared with Saline mice, Elastase mice showed a similarly increased mean chord length and pulmonary compliance at D14 and D21, while bronchoalveolar lavage cellularity was comparable between groups. Lung mechanics was similarly altered during mechanical ventilation in Elastase and Saline mice. Activated alveolar macrophages CD11bmid were present in lung parenchyma in both Elastase SV mice and Elastase MV mice at D14 but were absent at D21 and in Saline mice, indicating an inflammatory state with elastase at D14 only. At D14, Elastase MV mice showed a significant increase in percentage of neutrophils in total lung, as compared with Elastase SV mice. Furthermore, alveolar macrophages of Elastase MV mice at D14 overexpressed Gr1, and monocytes showed a trend to overexpression of CD62L, compared with Elastase SV mice. In an elastase-induced model of pulmonary emphysema, normal tidal volume mechanical ventilation may produce an increase in the proportion of pulmonary neutrophils, and an activation of alveolar macrophages and pulmonary monocytes. This response seems to be observed only when the emphysema model shows an underlying inflammation (D14), reflected by the presence of activated alveolar macrophages CD11bmid.
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Inflamación/patología , Macrófagos Alveolares/patología , Elastasa Pancreática/metabolismo , Enfisema Pulmonar/patología , Animales , Líquido del Lavado Bronquioalveolar/citología , Modelos Animales de Enfermedad , Inflamación/metabolismo , Pulmón/metabolismo , Pulmón/patología , Macrófagos Alveolares/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/metabolismo , Monocitos/patología , Neutrófilos/metabolismo , Neutrófilos/patología , Neumonía/metabolismo , Neumonía/patología , Enfisema Pulmonar/metabolismo , Porcinos , Ventiladores MecánicosRESUMEN
Quantitative RT-PCR (qRT-PCR) and Western blotting studies on transporters at the blood-brain barrier (BBB) of isolated brain microvessels have produced conflicting data on their cellular distribution. A major problem is identifying cells expressing the genes of interest, since isolated brain microvessels are composed of several cell types and may be contaminated with mRNA or proteins from astrocytes and neurons. We isolated rat brain microvessels and examined microscopically samples at each step of isolation to evaluate microvessel purity. The expression of specific markers of endothelial cells (Glut-1, Flk-1), pericytes (Ng2), neurons (synaptophysin, Syn) and astrocytes (Gfap) was measured by qRT-PCR in order to select the protocol giving the least astrocyte and neuron mRNAs and the most endothelial mRNAs. We also evaluated the gene expression of drug transporters (Mdr1a, Mdr1b, Mrp1-5, Bcrp and Oatp-2) at each step to optimize their location in cells at the BBB. The Mdr1a, Mrp4, Bcrp and Oatp-2 gene profiles were similar to those of endothelium markers. The profiles of Mrp2 and Mrp3 closely resembled that of Ng2. Mrp5 and Mrp1 expression was not increased in the microvessel-enriched fraction, suggesting that they are ubiquitously expressed throughout the cortex parenchyma. We also evaluated by Western blotting the expression of P-gp, Mrp2, Gfap and Syn in the cortex and in the purest obtained microvessel fraction. Our results showed that P-gp expression strongly increased in microvessels whereas Mrp2 was not detected in any of the fraction. Surprisingly, Gfap expression increased in isolated microvessels whereas Syn was not detected. Our results showed that the strategy consisting of identifying gene expression at different steps of the protocol is useful to identify cells containing mRNA at the BBB and give overall similar results with protein expression.
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Barrera Hematoencefálica/metabolismo , Proteínas Portadoras/genética , Arterias Cerebrales/metabolismo , Células Endoteliales/metabolismo , Microcirculación/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/genética , Masculino , Proteínas de Transporte de Membrana/genética , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Técnicas de Cultivo de Órganos/métodos , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Physiological studies of the blood-brain barrier (BBB) are often performed in rats. We describe the functional characterization of a reproducible in vitro model of the rat BBB and its validation for investigating mechanisms involved in BBB regulation. Puromycin-purified primary cultures of brain endothelial cells, co-cultured with astrocytes in the presence of hydrocortisone (HC) and cAMP, presented low sucrose permeability (< or =0.1 x 10(-3) cm/min) and high transendothelial electrical resistance (> or =270 Omega cm(2)). Expression of specific BBB markers and their transcripts was detected by immunostaining and RT-PCR, respectively: tight junction proteins (claudin-3 and -5, ZO-1 and occludin) and transporters (P-gp, Bcrp and Oatp-2). RT-PCR experiments demonstrated a role of treatment by astrocytes, HC and cAMP in regulation of the transcript level of tight junction proteins (claudin-5 and ZO-1) as well as transporters (Mdr1a, Mrp3, Mrp4, Bcrp, Glut-1), while transcript level of Mdr1b was significantly decreased. The functionality of efflux pumps (P-gp, Mrps and Bcrp) was demonstrated in the presence of specific inhibitors (PSC833, MK571 or Ko143, respectively) by (i) assessing the uptake of the common substrates rhodamine 123 and daunorubicin and (ii) evaluating apical to basolateral and basolateral to apical polarized transport of daunorubicin. In addition, a good correlation (R=0.94) was obtained between the permeability coefficients of a series of compounds of various lipophilicity and their corresponding in vivo rodent blood-brain transfer coefficients. Taken together, our results provide compelling evidence that puromycin-purified rat brain endothelial cells constitute a reliable model of the rat BBB for physiological and pharmacological characterization of BBB transporters.
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Astrocitos/fisiología , Barrera Hematoencefálica/fisiología , Permeabilidad Capilar/fisiología , Células Endoteliales/fisiología , Regulación de la Expresión Génica/fisiología , Análisis de Varianza , Animales , Animales Recién Nacidos , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/citología , Permeabilidad Capilar/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo/métodos , AMP Cíclico/farmacología , Impedancia Eléctrica , Regulación de la Expresión Génica/efectos de los fármacos , Hidrocortisona/farmacología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Modelos Animales , Transporte de Proteínas/efectos de los fármacos , Transporte de Proteínas/fisiología , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
Obstructive sleep apnea (OSA) syndrome is a common and often life-altering sleep-related breathing disorder. It not only adversely affects cardiovascular health, but the quality of life of these patients is also often significantly compromised. They experience excessive daytime sleepiness and poor cognitive, social and exercise performance. Furthermore, they often have marital problems with increased divorce rates, depression, and poor job performance.Our purpose in writing this review is to highlight the various neuropsychiatric domains that are affected in OSA patients and to emphasize that identifying and treating this condition can significantly improve the quality of life of these individuals. In recent years there has been ample evidence supporting the role of treatment for OSA to improve cardiovascular outcomes. We provide similar evidence supporting the treatment of OSA to improve health-related quality of life outcomes for these patients. Surgical, non-surgical and pharmacologic modalities are currently available as effective options for the treatment of OSA, with continuous positive airway pressure therapy appearing to be the most promising.
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Calidad de Vida , Apnea Obstructiva del Sueño , Presión de las Vías Aéreas Positiva Contínua , HumanosRESUMEN
The breast cancer resistance protein (BCRP/ABCG2) is, like P-glycoprotein (P-gp), a member of the ABC family of drug transporters. These proteins actively transport various anticancer drugs from cells, causing multidrug resistance. The physiological expression of P-gp/ABCB1 at the blood-brain barrier (BBB) effectively restricts the brain uptake of many antitumor drugs by mediating their active efflux from the brain to the blood vessel lumen. However, little is known about the function of Abcg2 at the BBB in vivo. We used in situ brain perfusion to measure the uptake of two known Abcg2 substrates, prazosin and mitoxantrone, and the nonsubstrate vinblastine by the brains of wild-type and P-gp-deficient mutant mdr1a(-/-) mice with or without the P-gp/Abcg2 inhibitor GF120918 or the P-gp inhibitor PSC833. P-gp had no effect on the brain transport of prazosin and mitoxantrone at the mouse BBB, but wild-type and P-gp-deficient mouse brains perfused with GF120918 or a high concentration of prazosin showed carrier-mediated effluxes of prazosin and mitoxantrone from the brain that did not involve P-gp. In contrast, the brain uptake of vinblastine was restricted only by P-gp and not by Abcg2 at the BBB. The amounts of abcg2 mRNA in cortex homogenates and capillary-enriched fractions of wild-type and mdr1a(-/-) mouse brains were measured by real-time quantitative reverse transcription-PCR. There was approximately 700-times more abcg2 mRNA in brain microvessels than in the cortex of the wild-type mice, confirming that Abcg2 plays an important role at the BBB. There was also approximately 3 times more abcg2 mRNA in the microvessels from P-gp-deficient mutant mouse brains than in the microvessels of wild-type mouse brains. These findings confirm that Abcg2 is a physiological transporter at the BBB that restricts the permeability of the brain to its substrates in vivo. Lastly, the defective P-gp in the mutant mdr1a(-/-) mice was associated with increased abcg2 mRNA at the BBB and a greater export of prazosin and mitoxantrone from the brain, as measured in the P-gp-deficient mice versus the wild-type mice.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Barrera Hematoencefálica/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/deficiencia , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/deficiencia , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/biosíntesis , Transportadoras de Casetes de Unión a ATP/genética , Animales , Transporte Biológico Activo , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Masculino , Ratones , Ratones Noqueados , Mitoxantrona/farmacocinética , Prazosina/farmacocinética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Vinblastina/farmacocinéticaRESUMEN
A 20 kg German shepherd dog was presented to a French veterinary teaching hospital for seizures and hyperthermia. The dog had returned 1 month previously from a six-month stay in Senegal and sub-Saharan Africa. Biochemistry and haematology showed severe hypoglycaemia (0.12 g/L), anaemia and thrombocytopenia. Despite administration of large amounts of glucose (30 mL of 30% glucose IV and 10 mL of 70% sucrose by gavage tube hourly), 26 consecutive blood glucose measurements were below 0.25 g/L (except one). Routine cytological examination of blood smears revealed numerous free extracytoplasmic protozoa consistent with Trypanosoma congolense. PCR confirmed a Trypanosoma congolense forest-type infection. Treatment consisted of six injections of pentamidine at 48-hour intervals. Trypanosomes had disappeared from the blood smears four days following the first injection. Clinical improvement was correlated with the normalization of laboratory values. The infection relapsed twice and the dog was treated again; clinical signs and parasites disappeared and the dog was considered cured; however, 6 years after this incident, serological examination by ELISA T. congolense was positive. The status of this dog (infected or non-infected) remains unclear. Hypoglycaemia was the most notable clinical feature in this case. It was spectacular in its severity and in its refractory nature; glucose administration seemed only to feed the trypanosomes, indicating that treatment of hypoglycaemia may in fact have been detrimental.
Asunto(s)
Enfermedades de los Perros/parasitología , Hipoglucemia/veterinaria , Parasitemia/veterinaria , Trypanosoma congolense/aislamiento & purificación , Tripanosomiasis Africana/veterinaria , África del Sur del Sahara , Animales , Antiprotozoarios/uso terapéutico , Enfermedades de los Perros/sangre , Perros , Femenino , Fiebre/etiología , Fiebre/veterinaria , Glucosa/efectos adversos , Glucosa/uso terapéutico , Hipoglucemia/tratamiento farmacológico , Hipoglucemia/etiología , Parasitemia/sangre , Parasitemia/diagnóstico , Parasitemia/tratamiento farmacológico , Pentamidina/uso terapéutico , Recurrencia , Convulsiones/etiología , Convulsiones/veterinaria , Senegal , Viaje , Tripanosomiasis Africana/sangre , Tripanosomiasis Africana/diagnóstico , Tripanosomiasis Africana/tratamiento farmacológicoRESUMEN
This study investigated the long-term effectiveness and safety of a variant of the transobturator vaginal tape inside-out technique for acquired urinary incontinence. Twelve spayed female dogs were operated over a 2 yr period. No intraoperative complications were encountered. Transient dysuria was the most common postoperative complication (7 out of 12 dogs). On the 12th day postoperatively, incontinence was completely cured in 11 out of 12 dogs (92%). At the time of the second evaluation (median follow-up time was 21 mo), patients classified as "cured," "greatly improved," or "improved" were 25, 50, and 25% of the total, respectively. At the time of either the fourth evaluation or at the time of death (median follow-up time was 52 mo), 50% of the bitches (6 out of 12) had the same results as previously but the other 50% had leakage that reappeared sporadically. A fistula appeared on the path of the tape in two bitches at 28 and 32 mo postsurgically. The technique presented is effective and more cost effective than the standard technique and could constitute an attractive alternative; however, it could be associated with an immediate postoperative dysuria, delayed fistula formation, and a partial recurrence of clinical signs.