Pancreatic Islet Transplantation into the Submandibular Gland: Our Experimental Experience and a Review of the Relevant Literature.

Pancreatic islet transplantation is a promising therapy for type 1 diabetes. Islet transplantation is clinically performed through intra-portal infusion, which is associated with several drawbacks, including poor engraftment. The histological resemblance between the submandibular gland and the pancreas renders it an attractive alternative site for islet transplantation. In this study, we refined the technique of islet transplantation into the submandibular gland to achieve good morphological features. Then, we transplanted 2600 islet equivalents into the submandibular glands of diabetic Lewis rats. Intra-portal islet transplantation was performed in diabetic rats as a control. Blood glucose levels were followed for 31 days, and an intravenous glucose tolerance test was performed. Immunohistochemistry was used to demonstrate the morphology of transplanted islets. Follow-up after transplantation showed that diabetes was cured in 2/12 rats in the submandibular group in comparison to 4/6 in the control group. The intravenous glucose tolerance test results of the submandibular and intra-portal groups were comparable. Immunohistochemistry showed large islet masses in the submandibular gland in all examined specimens with positive insulin staining. Our results show that submandibular gland tissue can support the islet function and engraftment but with considerable variability. Good morphological features were achieved using our refined technique. However, islet transplantation into rat submandibular glands did not demonstrate a clear advantage over conventional intra-portal transplantation.

A New Animal Model of Insulin-Glucose Dynamics in the Intraperitoneal Space Enhances Closed-Loop Control Performance.

Current artificial pancreas systems (AP) operate via subcutaneous (SC) glucose sensing and SC insulin delivery. Due to slow diffusion and transport dynamics across the interstitial space, even the most sophisticated control algorithms in on-body AP systems cannot react fast enough to maintain tight glycemic control under the effect of exogenous glucose disturbances caused by ingesting meals or performing physical activity. Recent efforts made towards the development of an implantable AP have explored the utility of insulin infusion in the intraperitoneal (IP) space: a region within the abdominal cavity where the insulin-glucose kinetics are observed to be much more rapid than the SC space. In this paper, a series of canine experiments are used to determine the dynamic association between IP insulin boluses and plasma glucose levels. Data from these experiments are employed to construct a new mathematical model and to formulate a closed-loop control strategy to be deployed on an implantable AP. The potential of the proposed controller is demonstrated via in-silico experiments on an FDA-accepted benchmark cohort: the proposed design significantly outperforms a previous controller designed using artificial data (time in clinically acceptable glucose range: 97.3±1.5% vs. 90.1±5.6%). Furthermore, the robustness of the proposed closed-loop system to delays and noise in the measurement signal (for example, when glucose is sensed subcutaneously) and deleterious glycemic changes (such as sudden glucose decline due to physical activity) is investigated. The proposed model based on experimental canine data leads to the generation of more effective control algorithms and is a promising step towards fully automated and implantable artificial pancreas systems.

Antiarrhythmic properties of atrial pacing.

Bradycardia, atrial stretch and dilatation, autonomic nervous system disorders, and the presence of triggers such as atrial premature contractions, are factors which predispose a person to paroxysmal AF. Atrial pacing not only eliminates bradycardia but also prevents atrial premature contractions and dispersion of refractoriness, which are a substrate for atrial fibrillation. As the prolonged duration of atrial activation during pacing, especially from locations changing the physiological pattern of this activation (right atrium lateral wall, right atrium appendage), negatively influences both a mechanical and an electrical function of the atria, the atrial pacing site affects an atrial arrhythmogenesis. A conventional atrial lead location in the right atrium appendage causes non-physiological activation propagation, resulting in a prolongation of the activation time of both atria. This location is optimal according to a passive fixation of the atrial lead but the available contemporary active fixation leads could potentially be located in any area of the atrium. There is growing evidence of the benefit of pacing, imitating the physiological propagation of impulses within the atria. It seems that the Bachmann's bundle pacing is the best pacing site within the atria, not only positively influencing the atrial mechanical function but also best fulfilling the so-called atrial resynchronization function, in particular in patients with interatrial conduction delay. It can be effectively achieved using only one atrial electrode, and the slight shortening of atrioventricular conduction provides an additional benefit of this atrial pacing site.

Avaliação da glicemia capilar na ponta de dedo versus locais alternativos: valores resultantes e preferência dos pacientes / Analysis of fingerstick capillary glycemia versus alternative site: results and patients preferences

O trabalho visa avaliar eficácia e a preferência dos pacientes na monitorização da glicemia capilar em locais alternativos: lóbulo de orelha, antebraço e panturrilha em relação à ponta de dedo. Foram avaliados 89 pacientes (39 M/50 F) com diabetes melito tipo 2 (DM2). A monitorização foi feita com glicosímetro digital (ACCU - CHEK Performa, Roche), lancetador ACCU-CHEK Multiclix, em grau 5 na face palmar da falange distal do 3º dedo da mão direita, porção inferior do lóbulo da orelha direita, antebraço direito e região superior da panturrilha direita. Não houve diferença da glicemia capilar na ponta de dedo em relação aos locais alternativos. A ponta de dedo foi o local mais doloroso. Quanto ao local de preferência, a orelha e a ponta de dedo foram os preferidos. A monitorização glicêmica em locais alternativos é simples, segura e eficaz, como a glicemia de ponta de dedo.

This paper evaluate the efficacy and patients preferences of glucose monitoring in alternatives sites: ear lobe, forearm and calf against conventional fingerstick. We studied 89 patients (39 M/ 50 F) with type 2 diabetes mellitus (DM2). Glucose monitoring was measured using a digital glucosimeter (ACCU - CHEK Performa, Roche), and ACCU-CHEK Multiclix lancetador, with grade 5 on the distal phalange on the right hand's third finger, inferior part of right ear lobe, right forearm and right calf. There was not statistical significance on the comparative analyzes of fingerstick and alternatives sites. There was more pain in fingerstick. The patients preferred the fingerstick and the ear lobe. Glucose monitoring in alternative sites is as simple, safe and efficient as fingerstick.