C1 inhibitor infusion modifies platelet activity in hereditary angioedema patients

CONTEXT: C1 inhibitor (C1-INH) is an alpha2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The alpha-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE). OBJECTIVE: To evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE. DESIGN: Assessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate. PATIENTS: In 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria. MEASUREMENTS: Platelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5 microM; collagen, 5 microg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay). RESULTS: After C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate- and collagen-induced platelet aggregation versus preinfusion values (maximum after 1-2 days; P <.001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively. CONCLUSIONS: These data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.     

The Mussel Mytilus galloprovincialis in the Bay of Naples: New Insights on Oogenic Cycle and Its Hormonal Control

The aim of the present article was to investigate the oogenic cycle of Mytilus galloprovincialis sampled in the Bay of Naples, and to immunolocalize 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and P450 aromatase, enzymes involved in the synthesis of two sex hormones: testosterone and 17β-estradiol. We demonstrate that the oogenic cycle starts in late summer-early fall and continues in early winter when the first event of spawning occurs; other spawning events take place until June, when the ovary is spent and contains a few empty ovarian follicles and numerous somatic cells, that is, adipogranular cells and vesicular connective tissue cells. During the oogenic cycle, apoptotic events occur at the level of oogonia, previtellogenic oocytes, as well as follicle cells; by contrast, necrosis events probably take place in vitellogenic oocytes, which, once degenerated, transfer their content to healthy oocytes. Finally, the present data demonstrate that 3β-HSD, 17β-HSD, and P450 aromatase are present in the ovary both during the reproductive and nonreproductive phases. The possible role of these enzymes during the Mytilus galloprovincialis reproductive cycle is discussed. Anat Rec, 302:1039–1049, 2019. © 2019 Wiley Periodicals, Inc.     

Neuroretinal dysfunction in patients affected by neurofibromatosis type 1

AIM: To examine neuroretinal function by using the multifocal electroretinography (mfERG) test in patients with neurofibromatosis type 1 (NF1) without optic pathway gliomas (OPGs). METHODS: This study was conducted on 35 patients (35 eyes) with NF1 and 30 healthy subjects (30 eyes) for the control group. Each subject underwent a complete ophthalmological examination including spectral domain-optical coherence tomography (SD-OCT) and mfERG. The 1.5-Tesla magnetic resonance imaging (MRI) scan of the brain was performed in NF1 patients to assess the presence of OPGs. All participants were recruited having a best corrected visual acuity (BCVA) of no less than 20/20 in each eye. The amplitude and implicit time of the P1 wave (first-order Kernel component) were evaluated on mfERG. Data analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual field. RESULTS: Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy controls, while the reduction was not significant in the 2 central degrees between the groups. A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group, with lower amplitudes detected in the nasal quadrants. No differences in the implicit times were recorded in the 2 central degrees and in the 4 quadrants as compared between NF1 patients and controls. CONCLUSION: Impaired neuroretinal function in NF1 patients is expressed in a decreased amplitude of the P1-wave between 2 and 25 central retinal degrees on mfERG. Altered intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate (cAMP) generation, can be involved. The possible use of mfERG as subclinical retinal damage indicator has a potential utility in clinical practice for the follow-up of NF1 patients.     

Diagnostic accuracy of ICD-9 code 780.2 for the identification of patients with syncope in the emergency department

Purpose

Syncope is a common condition that affects individuals of all ages and is responsible for 1–3% of all emergency department (ED) visits. Prospective studies on syncope are often limited by the exiguous number of subjects enrolled. A possible alternative approach would be to use of hospital discharge diagnoses from administrative databases to identify syncope subjects in epidemiological observational studies. We assessed the accuracy of the International Classification of Diseases, Ninth Revision (ICD-9) code 780.2 “syncope and collapse” to identify patients with syncope.

Methods

Patients in two teaching hospitals in Milan, Italy with a triage assessment for ED access that was possibly related to syncope were recruited in this study. We considered the index test to be the attribution of the ICD-9 code 780.2 at ED discharge and the reference standard to be the diagnosis of syncope by the ED physician.

Results

The sensitivity, specificity, positive and negative predictive values of the ICD-9 code 780.2 to identify patients with syncope were 0.63 (95% confidence interval [CI] 0.58–0.67), 0.98 (95% CI 0.98–0.99), 0.83 (95% CI 0.79–0.87) and 0.95 (95% CI 0.94–0.95), respectively.

Conclusions

The moderate sensitivity of ICD-9 code 780.2 should be considered when the code is used to identify patients with syncope through administrative databases.

     

A Kunitz proteinase inhibitor from corms of Xanthosoma blandum with bactericidal activity

Bacterial infections directly affect the world's population, and this situation has been aggravated by indiscriminate use of antimicrobial agents, which can generate resistant microorganisms. In this report, an initial screening of proteins with antibacterial activity from corms of 15 species of the Xanthosoma genus was conducted. Since Xanthosoma blandum corms showed enhanced activity toward bacteria, a novel protein with bactericidal activity was isolated from this particular species. Edman degradation was used for protein N-termini determination; the primary structure showed similarities with Kunitz inhibitors, and this protein was named Xb-KTI. This protein was further challenged against serine proteinases from different sources, showing clear inhibitory activities. Otherwise, no hemolytic activity was observed for Xb-KTI. The results demonstrate the biotechnological potential of Xb-KTI, the first proteinase inhibitor with antimicrobial activity described in the Xanthosoma genus.     

Granulin is a soluble cofactor for toll-like receptor 9 signaling

Toll-like receptor (TLR) signaling plays a critical role in innate and adaptive immune responses and must be tightly controlled. TLR4 uses LPS binding protein, MD-2, and CD14 as accessories to respond to LPS. We therefore investigated the presence of an analagous soluble cofactor that might assist in the recruitment of CpG oligonucleotides (CpG-ODNs) to TLR9. We report the identification of granulin as?an essential secreted cofactor that potentiates TLR9-driven responses to CpG-ODNs. Granulin, an unusual cysteine-rich protein, bound to CpG-ODNs and interacted with TLR9. Macrophages from granulin-deficient mice showed not only impaired delivery of CpG-ODNs to endolysosomal compartments, but?also decreased interaction of TLR9 with CpG-ODNs. As a consequence, granulin-deficient macrophages showed reduced responses to stimulation with CpG-ODNs, a trait corrected by provision of exogenous granulin. Thus, we propose that granulin contributes to innate immunity as a critical soluble cofactor for TLR9 signaling.     

Insulin resistance increases risk of carpal tunnel syndrome: a case-control study

Carpal tunnel syndrome (CTS) is one of the most common upper limb compression neuropathies. In only 50% of cases it is possible to identify a cause. Our objective was to determine the role of glucose metabolism abnormalities in idiopathic CTS. We identified 117 patients with idiopathic moderate or severe CTS and 128 controls. In all we evaluated glucose and insulin levels at fasting and after 2-h oral glucose tolerance test (2h-OGTT). In addition we determined insulin resistance (IR). Following OGTT the prevalence of glucose metabolism abnormalities was significantly higher in the CTS group (p = 0.001). IR was documented in 80% of patients, of whom 45% had impaired glucose tolerance, 14% newly diagnosed diabetes mellitus, and 20% IR only. Waist circumference and body mass index were also significantly increased in the CTS group. In this study, we focused on evidence that pre-diabetes may represent a risk factor for CTS. We proposed to determine IR as a rule in all patients with idiopathic CTS.     

Intra- and extra-cranial effects of transient blood pressure changes on brain near-infrared spectroscopy (NIRS) measurements

Brain near-infrared spectroscopy (NIRS) is an emerging neurophysiological tool that combines straightforward activity localization with cost-economy, portability and patient compatibility. NIRS is proving its empirical utility across specific cognitive and emotional paradigms. However, a potential limitation is that it is not only sensitive to haemodynamic changes taking place in the cortex, and task-related cardiovascular responses expressed in the perfusion of extracranial layers may be confounding. Existing literature reports correlations between brain NIRS and systemic blood pressure, yet it falls short of establishing whether in normal participants the blood pressure changes encountered in experimental settings can have confounding effects. Here, we tested this hypothesis by performing two experimental manipulations while recording from superficial occipital cortex, encompassing striate and extrastriate regions. Visual stimulation with reversing chequerboards evoked cortical haemodynamic responses. Simultaneously and independently, transient systemic blood pressure changes were generated through rapid arm-raising. Shallow-penetration NIRS recordings, probing only extra-cerebral tissues, highlighted close haemodynamic coupling with blood pressure. A different coupling pattern was observed in deep-penetration recordings directed at haemodynamic signals from visual cortex. In absence of blood-pressure changes, NIRS signals tracked differences in visual stimulus duration. However when blood pressure was actively manipulated, this effect was absent and replaced by a very large pressure-related response. Our observations demonstrate that blood pressure fluctuations can exert confounding effects on brain NIRS, through expression in extracranial tissues and within the brain itself. We highlight the necessity for continuous blood pressure monitoring alongside brain NIRS, and for further research on methods to correct for physiological confounds.     

Impact on Dyslipidemia of the Laparoscopic Ileal Interposition Associated to Sleeve Gastrectomy in Type 2 Diabetic Patients

Background  

Dyslipidemia is known to increase significantly the odds of major cardiovascular events in the general population. Its control becomes even more important in the type 2 diabetic (T2DM) population. Bariatric surgeries, especially gastric bypass, are effective in achieving long-term control of dyslipidemia in morbidly obese patients.