Placebo controlled phase II clinical trial: Safety and efficacy of combining intranasal insulin & acute exercise

A growing number of investigations are exploring the utility of intranasal insulin as a means of mitigating cognitive decline. However, as a basic tenant of dementia prevention programs is increasing physical activity, it is essential to obtain a preliminary assessment of the safety profile of combining intranasal insulin with physical activity; to ensure that undue risks are not incurred. Utilizing a randomized double-blind placebo-controlled design, a sample of 116 non-diabetic, fasted college-aged adults were randomly assigned to receive a dose of 0-to-120 IU of NovoLog (Insulin Aspart) before being randomized to 20 min of exercise or sitting control condition. The safety of intranasal insulin was assessed by examining the incidence of potential symptoms of hypoglycemia and changes in peripheral blood glucose. The efficacy of a combination therapeutic approach was assessed using behavioral measures of inhibition and sustained attention alongside neuroelectric indices of attentional engagement. The frequency of symptoms reported following administration of intranasal insulin were not observed to interact with exercise so as to make their occurrence any more or less prominent, nor was the frequency observed to relate to the dose of intranasal insulin. However, doses of intranasal insulin of 100 IU or more were observed to result in a 7-fold increase in the likelihood of a level 1 hypoglycemic event for those individuals in the exercise condition. This study provides preliminary evidence to suggest that exercise is not associated with an increase in risk when combined with lower doses of intranasal insulin.

Clinical trial registration The trial is registered at ClinicalTrials.gov, number NCT04292535.

     

Splenic infarction secondary to acute pancreatitis

BACKGROUND AND OBJECTIVE: the close anatomic relationship of the pancreas with the splenic vessels and the spleen is responsible for splenic complications in the course of acute pancreatitis. Our objective was to report two cases of severe acute pancreatitis complicated by splenic infarction. PATIENTS: in a three-month period of time two patients were diagnosed with splenic infarction secondary to acute pancreatitis. In both cases splenic infarction diagnosis and follow-up were carried out using computed tomography. RESULTS: in the first case images clearly showed a narrowing of the splenic artery due to the inflammatory pancreatic condition. In the second case no involvement of the splenic vessels could be demonstrated, hence the only possible etiological explanation was a hypercoagulability state generated by pancreatitis. CONCLUSIONS: it would be advisable that splenic complications were added to the list of relevant extrapancreatic manifestations. CT is very useful for the diagnosis and follow-up of splenic complications arising in acute pancreatitis.     

Acute Chagas' disease: immunohistochemical characteristics of T cell infiltrate and its relationship with T. cruzi parasitic antigens

OBJECTIVE: The present work analysed endomyocardial biopsies of patients with acute Chagas' disease in order to evaluate the frequency and intensity of T. cruzi antigens, CD4+ and CD8+ T cells to determine the characteristics of this recurrent disease in Venezuela. MATERIAL AND METHODS: Twelve endomyocardial biopsies of patients with Chagas' disease, 12 to 51 years old, (7M and 5F) were analysed. T. cruzi antigens and CD4+ (helper) and CD8+ (cytotoxic-suppressor) T cells were detected by the immunoperoxidase technique.The presence and intensity of lymphocytic myocarditis was evaluated according to the degree of myocardial fibre injury caused by inflammatory infiltrate. RESULTS: Myocarditis was present in 100% of the cases. The mean numbers of CD4+ T cell and CD8+ T cell were 11.00 (+/- 10.29); 14.69 (+/- 13.08) and the CD4/CD8 T cell ratio was 0.75. T. cruzi antigens were detected in 58%. There was a good correlation between the numbers of CD4 and CD8 T cells of each case and a lack of correlation with the amount of T. cruzi antigens. CONCLUSION: All patients with acute Chagas' disease show some degree of myocarditis that seems to be directly related to the presence of parasitic antigens. Both CD4 and CD8 T cells participate in this process.We are following these patients to see if patients with severe myocarditis and more parasite antigens in the acute phase will develop chronic heart failure.     

CD40 Induces Anti-Toxoplasma gondii Activity in Nonhematopoietic Cells Dependent on Autophagy Proteins

Toxoplasma gondii infects both hematopoietic and nonhematopoietic cells and can cause cerebral and ocular toxoplasmosis, as a result of either congenital or postnatally acquired infections. Host protection likely acts at both cellular levels to control the parasite. CD40 is a key factor for protection against cerebral and ocular toxoplasmosis. We determined if CD40 induces anti-T. gondii activity at the level of nonhematopoietic cells. Engagement of CD40 on various endothelial cells including human microvascular brain endothelial cells, human umbilical vein endothelial cells, and a mouse endothelial cell line as well as human and mouse retinal pigment epithelial cells resulted in killing of T. gondii. CD40 stimulation increased expression of the autophagy proteins Beclin 1 and LC3 II, enhanced autophagy flux, and led to recruitment of LC3 around the parasite. The late endosomal/lysosomal marker LAMP-1 accumulated around the parasite in CD40-stimulated cells. This was accompanied by killing of T. gondii dependent on lysosomal enzymes. Accumulation of LAMP-1 and killing of T. gondii were dependent on the autophagy proteins Beclin 1 and Atg7. Together, these studies revealed that CD40 induces toxoplasmacidal activity in various nonhematopoietic cells dependent on proteins of the autophagy machinery.     

Sequence Conservation of the Region Targeted by the Abbott RealTime HBV Viral Load Assay in Clinical Specimens

The Abbott RealTime HBV assay targets the N-terminal region of the S gene. Here we analyzed the sequence variability of the assay target region from >2,100 clinical specimens. Thermodynamic modeling of the percentage of bound primer/probe at the assay annealing temperature was performed to assess the potential effect of sequence variability.     

Enzymatic synthesis and electrochemical characterization of sodium 1,2-naphthoquinone-4-sulfonate-doped PEDOT/MWCNT composite

The development of novel materials with improved functional characteristics for supercapacitor electrodes is of current concern and calls for elaboration of innovative approaches. We report on an eco-friendly enzymatic synthesis of a composite based on poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-walled carbon nanotubes (MWCNTs). The redox active compound, sodium 1,2-naphthoquinone-4-sulfonate (NQS), was used as a dopant for the backbone of the polymer. Oxidative polymerization of 3,4-ethylenedioxythiophene (EDOT) was catalyzed by a high redox potential laccase from the fungus Trametes hirsuta. Atmospheric oxygen served as an oxidant. A uniform thin layer of NQS-doped PEDOT formed on the surface of MWCNTs as a result of the enzymatic polymerization. The PEDOT–NQS/MWCNT composite showed a high specific capacitance of ca. 575 F g⁻¹ at a potential scan rate of 5 mV s⁻¹ and an excellent cycling stability within a potential window between −0.5 and 1.0 V, which makes it a promising electrode material for high-performance supercapacitors.

The use of redox active NSQ as a dopant of PEDOT dramatically increases the specific capacitance and cyclic stability of enzymatically synthesized PEDOT–NSQ/MWCNT composite.