Reconstruction of the adult hemifacial microsomia patient with temporomandibular joint total joint prosthesis and orthognathic surgery

HFM patients' reconstruction has always been a challenge for maxillofacial surgeons, and numerous reconstructive techniques have been described. Surgical treatment depends on the patient's age and contemplates Temporomandibular Joint (TMJ) reconstruction in conjunction with orthognathic surgery, usually necessary following completion of growth to maximize the functional and esthetic results. Distraction osteogenesis had gained popularity as valid alternative in growing patients, but the two primary methods to reconstruct the TMJs involve the use of autogenous, using free or microvascular bone grafts, or alloplastic graft, but there is no widely accepted method

Organ donor pancreases for the study of human islet cell histology and pathophysiology: a precious and valuable resource

Direct in vivo assessment of pancreatic islet-cells for the study of the pathophysiology of diabetes in humans is hampered by anatomical and technological hurdles. To date, most of the information that has been generated is derived from histological studies performed on pancreatic tissue from autopsy, surgery, in vivo biopsy or organ donation. Each approach has its advantages and disadvantages (as summarised in this commentary); however, in this edition of Diabetologia, Kusmartseva et al (https://doi.org/10.1007/s00125-017-4494-x) provide further evidence to support the use of organ donor pancreases for the study of human diabetes. They show that length of terminal hospitalisation of organ donors prior to death does not seem to influence the frequency of inflammatory cells infiltrating the pancreas and the replication of beta cells. These findings are reassuring, demonstrating the reliability of this precious and valuable resource for human islet cells research

Synthesis and characterization of non-bridging mono- and bis-σ-η1-alkynyl derivatives of the phosphido-bridged hexaplatinum core [Pt6(μ-PBut2)4(CO)4]2+

Several mono- or bis-alkynyl derivatives of general formula Pt6(μ-PBut2)4(CO)4X(CC–R), Pt6(μ-PBut2)4(CO)4(CC–R)2 or Pt6(μ-PBut2)4(CO)4(CC–R)(CC–R′) were obtained under Sonogashira type conditions. The new clusters have been characterized with microanalysis and using IR and multinuclear NMR spectroscopy. The crystal and molecular structures of Pt6(μ-PBut2)4(CO)4(CC–R)2 (R = H, C6H4-4-n-C5H11) are presented and electrochemical and spectroelectrochemical studies of some representative compounds are also reported

Insulin secretory granules labelled with phogrin-fluorescent proteins show alterations in size, mobility and responsiveness to glucose stimulation in living β-cells

The intracellular life of insulin secretory granules (ISGs) from biogenesis to secretion depends on their structural (e.g. size) and dynamic (e.g. diffusivity, mode of motion) properties. Thus, it would be useful to have rapid and robust measurements of such parameters in living β-cells. To provide such measurements, we have developed a fast spatiotemporal fluctuation spectroscopy. We calculate an imaging-derived Mean Squared Displacement (iMSD), which simultaneously provides the size, average diffusivity, and anomalous coefficient of ISGs, without the need to extract individual trajectories. Clustering of structural and dynamic quantities in a multidimensional parametric space defines the ISGs’ properties for different conditions. First, we create a reference using INS-1E cells expressing proinsulin fused to a fluorescent protein (FP) under basal culture conditions and validate our analysis by testing well-established stimuli, such as glucose intake, cytoskeleton disruption, or cholesterol overload. After, we investigate the effect of FP-tagged ISG protein markers on the structural and dynamic properties of the granule. While iMSD analysis produces similar results for most of the lumenal markers, the transmembrane marker phogrin-FP shows a clearly altered result. Phogrin overexpression induces a substantial granule enlargement and higher mobility, together with a partial de-polymerization of the actin cytoskeleton, and reduced cell responsiveness to glucose stimulation. Our data suggest a more careful interpretation of many previous ISG-based reports in living β-cells. The presented data pave the way to high-throughput cell-based screening of ISG structure and dynamics under various physiological and pathological conditions

Pancreatic Beta Cell Identity in Humans and the Role of Type 2 Diabetes

Pancreatic beta cells uniquely synthetize and release insulin. Specific molecular, functional as well as ultrastructural traits characterize their insulin secretion properties and survival phenotype. In this review we focus on human islet/beta cells, and describe the changes that occur in type 2 diabetes and could play roles in the disease as well as represent possible targets for therapeutical interventions. These include transcription factors, molecules involved in glucose metabolism and insulin granule handling. Quantitative and qualitative insulin release patterns and their changes in type 2 diabetes are also associated with ultrastructural features involving the insulin granules, the mitochondria, and the endoplasmic reticulum

Metabolic response of Insulinoma 1E cells to glucose stimulation studied by fluorescence lifetime imaging

A cascade of highly regulated biochemical processes connects glucose stimulation to insulin secretion in specialized cells of mammalian pancreas, the β-cells. Given the importance of this process for systemic glucose homeostasis, noninvasive and fast strategies capable to monitor the response to glucose in living cells are highly desirable. Here, we use the phasor-based approach to Fluorescence Lifetime IMaging (FLIM) microscopy to quantify the ratio between protein-bound and free Nicotinamide adenine dinucleotide (phosphate) species in their reduced form (NAD(P)H), and the Insulinoma cell line INS-1E as a β-like cellular model. Phasor-FLIM analysis shows that the bound/free ratio of NAD(P)H species increases upon pulsed glucose stimulation. Such response is impaired by 48-hours preincubation of cells under hyperglycemic conditions. Phasor-FLIM concomitantly monitors the appearance of long-lifetime species (LLS) as characteristic products of hyperglycemia-induced oxidative stress

A role for autophagy in β-cell life and death.

Autophagy is a vacuolar, self-digesting mechanism responsible for the removal of organelles and defined regions of the cytoplams. This process has, in general, a beneficial role for the cell, since it regulates the turnover of aged proteins and eliminates damaged structures. However, cells that undergo altered autophagy may be triggered to die in a non-apoptotic manner. As a matter of fact, in recent years it has become clear that dysregulated autophagy may be implicated in several disorders, such as cancer, neurodegenerative diseases and hepatic encephalopathy. We have recently shown that β-cells of type 2 diabetic subjects show signs of autophagy associated death, which may contribute to the overall loss of β-cell mass in type 2 diabetes. In addition, studies with cell lines and rodent models have demonstrated the importance of autophagy in β-cell function and survival. Altogether, the available evidence supports the view that autophagy is implicated in β-cell pathophysiology, and suggests that addressing the molecular mechanisms involved in autophagic regulation might provide clues for preventing or treating β-cell damage in diabetes

Capacitive Displacement Sensor for a Self-Sensing Shock-Absorber Piston-Cylinder Mechanism

Measurement of piston displacement is a common problem for any pneumatic or hydraulic device, like shock-absorber. Direct measurements are not always feasible because of mechanical constraints; most recent techniques rely on magnetic phenomena, introducing considerable complexity. In an attempt to achieve an economical and feasible solution, an intrinsic capacitive sensor is developed. Such sensors measure the capacitance between piston and cylinder, which is directly proportional to displacement. It is developed an oscillator stage to measure the unknown capacitance. The oscillator’s output is acquired by a microcontroller, conditioned and transformed into the estimated displacement. This paper focuses on the design methodology of the measurement stage, highlighting tradeoffs and optimizations. The sensor was developed for an automotive application in a commercial shock absorber: however, it can be extended to other devices where proper electrical isolation between cylinder and piston is provided. Mathematical models and experimental results are reported compared to a commercial position sensor

Alteration of beta-cell constitutive NO synthase activity is involved in the abnormal insulin response to arginine in a new rat model of type 2 diabetes.

We have previously obtained a new type 2 diabetic syndrome in adult rats given streptozotocin and nicotinamide, characterized by reduced beta-cell mass, partially preserved insulin response to glucose and tolbutamide and excessive responsiveness to arginine. We have also established that the neuronal isoform of constitutive NO synthase (nNOS) is expressed in beta-cells and modulates insulin secretion. In this study, we explored the kinetics of glucose- and arginine-stimulated insulin release in perifused isolated islets as well as the effect of N-omega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, to get insight into the possible mechanisms responsible for the arginine hypersensitivity observed in vitro in this and other models of type 2 diabetes. A reduced first phase and a blunted second phase of insulin secretion were observed upon glucose stimulation of diabetic islets, confirming previous data in the isolated perfused rat pancreas. Exposure of diabetic islets to 10 mM arginine, in the presence of 2.8 mM glucose, elicited a remarkable monophasic increment in insulin release, which peaked at 639 +/- 31 pg/islet/min as compared to 49 +/- 18 pg/islet/min in control islets (P << 0.01). The addition of L-NAME to control islets markedly enhanced the insulin response to arginine, as expected from the documented inhibitory effect exerted by nNOS activity in normal beta-cells, whereas it did not further modify the insulin secretion in diabetic islets, thus implying the occurrence of a defective nNOS activity in these islets. A reduced expression of nNOS mRNA was found in the majority but not in all diabetic islet preparations and therefore cannot totally account for the absence of L-NAME effect, that might also be ascribed to post-transcriptional mechanisms impairing nNOS catalytic activity. In conclusion, our results provide for the first time evidence that functional abnormalities of type 2 experimental diabetes, such as the insulin hyper-responsiveness to arginine, could be due to an impairment of nNOS expression and/or activity in beta-cell