Electrocardiographic changes of ST-elevation myocardial infarction in patients with complete occlusion of the left main trunk without collateral circulation: Differential diagnosis and clinical considerations

Acute coronary syndromes due to involvement of the left main trunk usually present with subtotal occlusion and electrocardiographic pattern with predominant ST depression (non-ST-elevation myocardial infarction). The cases with complete occlusion frequently present an ST-elevation myocardial infarction pattern, but these patients usually die before reaching the hospital. We present a series of 7 patients with total left main trunk occlusion without collateral circulation showing ST-elevation myocardial infarction pattern. The electrocardiographic pattern is similar to left anterior descending coronary artery proximal occlusion to first septal and first diagonal but without ST elevation in V(1) and aVR because of left circumflex coronary artery compromise. In 4 (60%) of 7 of cases, there is also advanced right bundle-branch block plus superoanterior hemiblock. Despite severe clinical state at entrance (5/7 presented cardiac arrest/cardiogenic shock), 3 patients (43%) survived after percutaneous coronary intervention.     

Safety in the Use of Dexmedetomidine (Precedex) for Deep Brain Stimulation Surgery: Our Experience in 23 Randomized Patients

Objective: Evaluation of safety and efficacy of dexmedetomidine in deep brain stimulation (DBS) surgery. Materials and Methods: A cohort of 23 patients, candidates for DBS for Parkinson's disease, Tourette syndrome, or obsessive‐compulsive disorder, was randomized in two groups: dexmedetomidine group and control group. Standard anesthesiologic parameters were recorded and analyzed, together with the need for other medications. A ten‐degree scale (visual analog scale) assessing patient discomfort during DBS also was recorded at the end of surgery. Results: The results demonstrated good stability of intraoperative monitoring: no respiratory depression and good overall cooperation with the neurologist, while no side‐effects were recorded. Conclusions: Our conclusion is that dexmedetomidine should be considered as a valuable option for sedation in poorly collaborating patients undergoing DBS surgery.     

S100B and schizophrenia

The research for peripheral biological markers of schizophrenia, although abundant, has been unfruitful. In the last 2 decades, the S100B protein has made its own room in this area of research. S100B is a calcium‐binding protein that has been proposed as a marker of astrocyte activation and brain dysfunction. Research results on S100B concentrations and schizophrenia clinical diagnosis are very consistent; patients with schizophrenia have higher S100B concentrations than healthy controls. The results regarding schizophrenia subtypes and clinical characteristics are not as conclusive. Age of patients, body mass index, illness duration and age at onset have been found to show no correlation, a positive correlation or a negative correlation with S100B levels. With respect to psychopathology, S100B data are inconclusive. Positive, negative and absence of correlation between S100B concentrations and positive and negative psychopathology have been reported. Methodological biases, such as day/night and seasonal variations, the use of anticoagulants to treat biological samples, the type of analytical technique to measure S100B and the different psychopathological scales to measure schizophrenia symptoms, are some of the factors that should be taken into account when researching into this area in order to reduce the variability of the reported results. The clinical implications of S100B changes in schizophrenia remain to be elucidated.     

Sudden Stopping in Patients with Cerebellar Ataxia

Stopping during walking, a dynamic motor task frequent in everyday life, is very challenging for ataxic patients, as it reduces their gait stability and increases the incidence of falls. This study was conducted to analyse the biomechanical characteristics of upper and lower body segments during abrupt stopping in ataxic patients in order to identify possible strategies used to counteract the instability in the sagittal and frontal plane. Twelve patients with primary degenerative cerebellar ataxia and 12 age- and sex-matched healthy subjects were studied. Time–distance parameters, dynamic stability of the centre of mass, upper body measures and lower joint kinematic and kinetic parameters were analysed. The results indicate that ataxic patients have a great difficulty in stopping abruptly during walking and adopt a multi-step stopping strategy, occasionally with feet parallel, to compensate for their inability to coordinate the upper body and to generate a well-coordinated lower limb joint flexor–extensor pattern and appropriate braking forces for progressively decelerating the progression of the body in the sagittal plane. A specific rehabilitation treatment designed to improve the ability of ataxic patients to transform unplanned stopping into planned stopping, to coordinate upper body and to execute an effective flexion–extension pattern of the hip and knee joints may be useful in these patients in order to improve their stopping performance and prevent falls.     

Cyclodextrin Protects Podocytes in Diabetic Kidney Disease

Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD⁺) when compared with diabetic patients with normoalbuminuria (DKD⁻) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes.Diabetic kidney disease (DKD) is responsible for nearly half of the incidents of end-stage kidney disease in the U.S. (1), yet our current understanding of the pathophysiological processes responsible for DKD has led to limited improvements in patient outcomes. Multifactorial intervention reduces the rate of progression of DKD but does not prevent end-stage kidney disease in type 1 (T1D) or type 2 diabetes (T2D) (2,3). A key factor for this translation gap is the current lack of adequate mechanistic insight into DKD in humans.The kidney glomerulus is a highly specialized structure that ensures the selective ultrafiltration of plasma so that essential proteins are retained in the blood (4). Podocytes are glomerular epithelial cells that contribute to the glomerular filtration barrier through a tight regulation of actin cytoskeleton remodeling (4). Currently, the diagnosis of DKD relies on the detection of microalbuminuria (5). However, a growing body of evidence suggests that key histological lesions precede the development of albuminuria (6,7); among them, decreased podocyte number (podocytopenia) has been described as an independent predictor of DKD progression (8–12). Although we have previously shown that podocyte insulin resistance and susceptibility to apoptosis is already present at the time of onset of microalbuminuria in experimental models of DKD, the cause of podocyte injury in early DKD remains unknown (13).We used a previously established cell-based assay in which differentiated human podocytes are exposed to 4% patient sera for 24 h (14) to identify new pathways and targets in DKD. Podocytes exposed to the sera of patients with DKD showed increased cholesterol accumulation in association with downregulation of ATP-binding cassette transporter 1 (ABCA1) expression that was independent of circulating cholesterol.ABCA1 is a major regulator of cellular cholesterol homeostasis by mediating efflux to lipid-poor apolipoprotein acceptors in the bloodstream (15). ABCA1 genetic variants are strongly associated with the risk of coronary artery disease (16). Furthermore, the capacity of patient sera to induce ABCA1-mediated cholesterol efflux in macrophages is impaired in patients with T2D and incipient or overt nephropathy (17). Excessive cholesterol accumulation has been described in glomeruli of rodent models of T1D and T2D (18–20) and may contribute to DKD development and progression. Finally, inactivating mutations of ABCA1 result in Tangier disease, which causes premature atherosclerosis and proteinuria (21).Although interventions that increase ABCA1 expression (such as liver X receptor agonists) may be beneficial in DKD, they have a relatively high incidence of adverse events (22) as well as intrinsic lipogenic effects (23). We used β-cyclodextrins, cyclic oligosaccharides consisting of seven β(1-4)-glucopyranose rings, to remove cholesterol from differentiated human podocytes in vitro and from diabetic animals in vivo. The exact mechanism by which cyclodextrins (CDs) remove cholesterol from cells is not completely understood, but the formation of cholesterol/CD inclusion complexes at the membrane surface plays an important role in this process (24).We hypothesized that 2-hydroxypropyl-β-cyclodextrin, which was recently approved by the U.S. Food and Drug Administration (FDA) for the cure of Niemann-Pick disorder (25,26), would be an effective way to sequester cholesterol and to protect podocytes from cholesterol-dependent damage in DKD in vivo and in vitro.     

Low-dose sirolimus-eluting hydroxyapatite coating on stents does not increase platelet activation and adhesion ex vivo

We previously found paclitaxel-eluting polymer-coated stents causing more human platelet-monocyte complex formation than bare metal stents in vitro. Presently, we examined patterns of platelet activation and adhesion after exposure to 6 nanofilm HAp-coated (HAp-nano) stents, 6 HAp-microporous-coated (HAp-micro) stents, 5 HAp sirolimus-eluting microporous-coated (HAp-SES) stents and 5 cobalt-chromium stents (BMS) deployed in an in vitro flow system. Blood obtained from healthy volunteers was circulated and sampled at 0, 10, 30 and 60 min. By flow cytometry, there were no significant differences in P-Selectin expression between the 4 stent types (HAp-nano = 32.5%; HAp-micro = 42.5%, HAp-SES = 10.23%, BMS = 7% change from baseline at 60 min, p = NS); PAC-1 antibody binding (HAp-nano = 11.8%; HAp-micro = 2.9%, HAp-SES = 18%, BMS = 6.4% change from baseline at 60 min, p = NS) or PMC formation (HAp-nano = 21.6%; HAp-micro = 4%, HAp-SES = 6.6%, BMS = 17.4% change from baseline at 60 min, p = NS). The 4 stent types did not differ in the average number of platelet clusters >10 μm in diameter by SEM (HAp-nano = 2.39 ± 5.75; HAp-micro = 2.26 ± 3.43; HAp-SES = 1.93 ± 3.24; BMS = 1.94 ± 2.41, p = NS). The majority of the struts in each stent group were only mildly covered by platelets, (HAp-nano = 80%, HAp-micro = 61%, HAp-SES = 78% and BMS = 52.1%, p = NS). The HAp-microporous-coated stents (ECD) attracted slightly more proteinaceous material than bare metal stents (HAp-micro = 35% struts with complete protein coverage, P < 0.0001 vs. other 3 stent types). In conclusion, biomimetic stent coating with nanofilm or microporous hydroxyapatite, even when eluting low-dose sirolimus, does not increase the platelet activation in circulating human blood, or platelet adhesion to stent surface when compared to bare metal stents in vitro.