Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions.

The spatial and temporal distributions of proteins are critical to protein function, but cannot be directly assessed by measuring protein bundance. Here we describe a mass spectrometry-based proteomics strategy, Simultaneous Proteome Localization and Turnover (SPLAT), to measure concurrently protein turnover rates and subcellular localization in the same experiment. Applying the method, we find that unfolded protein response (UPR) has different effects on protein turnover dependent on their subcellular location in human AC16 cells, with proteome-wide slowdown but acceleration among stress response proteins in the ER and Golgi. In parallel, UPR triggers broad differential localization of proteins including RNA-binding proteins and amino acid transporters. Moreover, we observe newly synthesized proteins including EGFR that show a differential localization under stress than the existing protein pools, reminiscent of protein trafficking disruptions. We next applied SPLAT to an induced pluripotent stem cell derived cardiomyocyte (iPSC-CM) model of cancer drug cardiotoxicity upon treatment with the proteasome inhibitor carfilzomib. Paradoxically, carfilzomib has little effect on global average protein half-life, but may instead selectively disrupt sarcomere protein homeostasis. This study provides a view into the interactions of protein spatial and temporal dynamics and demonstrates a method to examine protein homeostasis regulations in stress and drug response.

Soporte nutricional especializado en un paciente con úlceras por presión: un informe de caso / Specialized nutritional support in a patient with pressure ulcers: a case report

Las úlceras por presión son lesiones de la piel y/o del tejido subyacente. El soporte nutricional adecuado constituye parte del tratamiento de estas lesiones. El objetivo de este reporte es demostrar la eficacia del soporte nutricional como factor coadyuvante en la recuperación de éstas. Paciente masculino de 29 años de edad que ingresó al hospital con diagnóstico de neuroinfección. Durante su estadía desarrolló una úlcera en la región sacra. Fue tratado con nutrición enteral por sonda nasoentérica que incluyó dieta y soporte nutricional hiperproteicos enriquecido con glutamina y arginina; posteriormente se brindó colágeno hidrolizado. A los 36 días tras la aparición de la úlcera, ésta es recuperada. Luego de 4 meses, el paciente fue dado de alta. La intervención nutricional fue crucial en la recuperación de la úlcera. Se enfatiza la necesidad de prevenirlas a través de un monitoreo oportuno y adecuado.

Pressure ulcers are injuries to the skin and / or the underlying tissue. Opportune nutritional support is part of the treatment of these injuries. This report aims to demonstrate the efficacy of nutritional support as a contributing factor in this ulcer recovery. A 29-year-old male patient was admitted to the hospital with a diagnosis of neuroinfection. During his stay, he developed a pressure ulcer in the sacral region. He was treated with enteral nutrition via a nasoenteric tube that included a hyperprotein diet and nutritional support enriched with glutamine and arginine; subsequently, hydrolyzed collagen was provided. Thirty-six days after the development of the pressure ulcer, it has recovered. After four months, the patient was discharged. The nutritional intervention was crucial in the recovery of UPP. The need to prevent this type of ulcers through timely and adequate monitoring is emphasized.

Efeito agudo do verapamil na cardiopatia hipertensiva. / Acute effect of verapamil in hypertensive cardiopathy

Foram estudados 16 pacientes hipertensos, 7 do sexo masculino, com idade media de 56 anos (28 a 76 anos). Apos uso de 0,15 mg/ kg de verapamil por via venosa, houve aumento significativo da pressao media no atrio direito, de 2,3 + ou - 0,6 mm Hg para 3,4 + ou - 0,6 mm Hg (P < 0,05), queda significativa das pressoes aortica maxima, de 165 + ou - 5,4 mm Hg para 136 +ou- 5,4 mm Hg, aortica minima de 87 +/- 3 mm Hg para Hg e aortica media de 119 +/- 4,6 mm Hg para 96 +/- 4,6 mm Hg (P < 0,001), diminuicao da resistencia vascular sistemica de 20 +/- 1 para 15 +/- 1 unidades (P < 0, 001) e da dp/dt maxima do ventriculo esquerdo, de 2350 +/- 115 mm Hg/s para 1923 +/- 115 mm Hg/s (P < 0,05). Observou-se ainda uma tendencia ao aumento do indice cardiaco. A frequencia cardiaca, a pressao media da arteria pulmonar, a pressao diastolica final do ventriculo esquerdo, os volumes diastolicos e sistolicos finais e a fracao de ejecao do ventriculo esquerdo nao se alteraram

Gastrostomía endoscópica percutánea (GEP): Dispositivo diseñado reutilizable (NAGEP) en técnica endoscópica de un tiempo. Estudio experimental en perros / Percutaneous endoscopic gastrostomy (GEP): designed reusable device (NAGEP) for one time endoscopic technique. Experimental study in dogs

INTRODUCTION: This aim of our experimental study was to demonstrate the versatility of our designed reusable decive for PEG and its future application in humans. MATERIALS AND METHODS: 20 mongrel dogs received enteral nutrition by a Foley tube placed by a single endoscopic technique using a reusable stainless steel designed decive, three reusable stainless steel designed decive, three reusable stainless steel dilators, an Olympus XQ20 video gastrointestinal endoscope, basic surgical equipment and surgical material. RESULTS: The procedure was successfully performed in all dogs under general anaesthesia. The duration of the whole procedure ranged from 10 to 18 min. The complications regardless by the PEG procedure were minimal. The Foley tube was retained by 15 days. CONCLUSIONS: The application of the stainless steel reusable designed decive for the PEG is safe, and presents several advantages. This technique for PEG placement could be used in the future due the characteristics of the designed device: durable and reusable for unlimited number of procedures.