Effects of fulminant hepatic encephalopathy on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase: comparison of the enzymes’ response to in vitro treatment with ammonia

Hepatic encephalopathy can be a life-threatening complication of fulminant hepatic failure. By understanding the pathophysiology involved in the induction of this neuropsychiatric disorder, future therapeutic and/or preventive attempts could be considered. In this study, an attempt has been made in order to shed more light on the mechanisms involved in the effects of thioacetamide (TAA)-induced fulminant hepatic encephalopathy on: (a) the adult rat brain total antioxidant status (TAS) and (b) the activities of acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase. Moreover, in vitro experiments were conducted in order to evaluate the possible role of ammonia (incubated as NH(4)Cl, in a toxic concentration of 3mM) in the observed effects of TAA-induced fulminant hepatic encephalopathy on the examined adult rat brain enzyme activities. Fulminant hepatic encephalopathy caused a significant decrease in TAS (-22%, p < 0.001) and the activity of Na(+),K(+)-ATPase (-26%, p < 0.001), but had non-significant effects on the whole brain AChE and Mg(2+)-ATPase activities. The in vitro experiments (conducted through a 3h incubation with ammonia), showed no significant alterations in any of the examined parameters. Our in vitro and in vivo findings suggest that alterations in AChE and Mg(2+)-ATPase activities are not involved in the pathophysiology of the adult-onset fulminant hepatic encephalopathy, while the observed Na(+),K(+)-ATPase inhibition could be a result of the oxidative stress, neurotransmission deregulation, and/or of the presence of other toxic substances (that appear to act as direct or indirect inhibitors of the enzyme) and not due to the excess accumulation of ammonia in the brain.     

Pulmonary capillary endothelial metabolic dysfunction: severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

OBJECTIVE: Pulmonary endothelial dysfunction is intertwined with the development and progression of pulmonary arterial hypertension (PAH). Pulmonary endothelium is an active metabolic tissue in healthy human subjects. This study was undertaken to determine the effects of PAH on pulmonary endothelial angiotensin-converting enzyme (ACE) activity and to identify differences between common PAH types, i.e., PAH related to connective tissue disease (PAH-CTD) versus idiopathic PAH (IPAH). METHODS: Nineteen patients with PAH-CTD, 25 patients with IPAH, and 23 control subjects were evaluated. The single-pass transpulmonary percent metabolism (%M) and hydrolysis (both reflecting enzyme activity per capillary) of an ACE synthetic substrate were determined. In addition, the calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), was determined. RESULTS: The %M values in patients with PAH-CTD (mean+/-SEM 53.6+/-3.6%) were significantly reduced compared with those in control subjects (P<0.01) and those in patients with IPAH (P<0.03), but were similar between the IPAH and control groups (mean+/-SEM 66.2+/-3.6% and 74.7+/-2.7%, respectively). Substrate hydrolysis was also significantly reduced in patients with PAH-CTD. The FCSA/BSA was significantly reduced in patients with PAH-CTD (mean+/-SEM 1,068+/-118 ml/minute/m2) and in patients with IPAH (1,443+/-186 ml/minute/m2) compared with that in controls (2,948+/-245 ml/minute/m2; P<0.01 for both). At a given cardiac index, the FCSA/BSA tended to be lower in the PAH-CTD group than in the IPAH group. Moreover, unlike in IPAH, a linear relationship between the FCSA/BSA and the diffusing capacity for carbon monoxide (DLCO) was observed in PAH-CTD (r=0.54, P<0.03). CONCLUSION: The metabolically functional pulmonary capillary bed appears to be reduced to an equal extent in PAH-CTD and IPAH. However, %M and hydrolysis appear to be reduced in PAH-CTD but not in IPAH, reflecting relatively diminished ACE activity on the pulmonary capillary endothelial cells of patients with PAH-CTD, and showing that pulmonary endothelial metabolic function differs between PAH types. This study also provides the first functional evidence that a reduced DLCO value in patients with PAH-CTD is related to the degree of FCSA loss.     

Left atrial appendage occlusion: Initial experience with the Amplatzer™ Amulet™

Background

The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicated device for percutaneous left atrial appendage (LAA) occlusion. The new device has been designed to facilitate the implantation process, improve the sealing performance and further reduce the risk of complications. The objective of the study was to describe the initial experience with the Amplatzer Amulet for percutaneous LAA occlusion.

Methods

This was a prospective single-center study of patients undergoing percutaneous LAA occlusion. The indication for LAA closure was a formal contraindication for oral anticoagulation or previous history of stroke due to INR lability. All procedures were done under general anesthesia and transesophageal echocardiography (TEE) guidance. Transthoracic echocardiography was performed 24 h after the procedure in order to rule out procedural complications before discharge. Further follow-up was done with a clinical visit and TEE at 1–3 months.

Results

Between July-2012 and June-2013, 25 patients with a mean CHA₂DS₂-VASC of 4.3 ± 1.7 underwent LAA occlusion with the Amplatzer Amulet. The device was successfully implanted in 24 patients (96%) without any procedural stroke, pericardial effusion or device embolization. None of the patients presented any clinical event at follow-up. Follow-up TEE showed complete LAA sealing in all patients with no residual leaks > 3 mm and no device embolization. One patient (4.1%) presented a device thrombosis at follow-up without clinical expression.

Conclusion

In this initial series of patients, the Amulet showed a remarkable acute and short-term performance in terms of feasibility and safety as depicted by the high successful implantation rate and the low incidence of complications.     

Clinical importance of main pancreatic duct variants and possible correlation with pancreatic diseases

Abstract

Background: Except for pancreas divisum (PD), the prevalence of anatomic variants of the main pancreatic duct (MPD) seems to be insufficiently investigated. To date, their role in the occurrence of pancreatic exocrine insufficiency (PEI) and morphological changes suggestive of chronic pancreatitis (CP) has remained unclear.

Methods: A systematic review was performed, searching MEDLINE and Web of Science, limited to articles published between 1960 and 1 June 2019.

Results: Our review included a total number of 3234 subjects. The most common variant of MPD was type 3, followed by type 1, indicating MPD drainage pattern into major papilla (MP) as the most frequent. A sub-variant of type 3, known as ‘reverse pancreas divisum’ had a prevalence of 2.2%. Type 4 variant- PD, was found in 6.4% of all cases. The most common sub-variant of PD was complete PD, followed by incomplete PD and variant with MPD as only pancreatic duct. Type 5 variant (including ansa pancreatica) was present in 2.9% of subjects. Apart from one study with a significantly higher frequency of morphological changes suggestive of CP in patients with ansa pancreatica, the studies stated no significant association between pancreatic disease and MPD variants. Furthermore, only one study examined the influence of MPD variants on exocrine pancreatic function. Although equivocal, this association is most likely found to be insignificant.

Conclusion: To elucidate linkage between MPD variants and the occurrence of chronic pancreatitis and impairment of pancreatic exocrine function, further clinical investigations are warranted.     

Fascia lata allograft bridging of a rotator cuff tear in a rabbit animal model

Purpose:

Despite advances in surgical treatment options, large rotator cuff (r-c) tears still represent a challenge for orthopedic surgeons. The purpose of this study was to evaluate the temporary and spatial histological incorporation of fascia lata allografts, used for bridging artificially created defects of the r-c.

Materials and Methods:

Seventy-two rabbits were divided into two groups and a supraspinatus tendinous defect was created. Half of the rabbit population underwent repair only, while in the other half, the defect was bridged utilizing fascia lata allograft. The animals were euthanized at 2, 4, and 6 weeks postoperative. Half of the specimens were evaluated histologically and the other half underwent mechanical testing.

Results:

There was an increased remodeling activity, fibroblastic in growth and strong presence of collagen fibers observed at 6 weeks on both groups. A gradually increasing mechanical strength was noticed by week 6 and increased toughness was also found at the same time period. There was no significant difference observed between the two groups regarding their histological and mechanical properties.

Conclusions:

In the difficult scenario of a large irreparable tear where the simple suture of the remaining r-c is impossible, allograft bridging, could be used with satisfactory results.

Clinical Relevance:

Treatment Study, Level 1.     

Evaluation of foot hypoperfusion and estimation of percutaneous transluminal angioplasty outcome in patients with critical limb ischemia using intravoxel incoherent motion microperfusion MRI

Objectives:To emerge hypoperfusion of lower limbs in patients with critical limb ischemia (CLI) using Intravoxel Incoherent Motion microperfusion magnetic resonance imaging (IVIM-MRI). Moreover to examine the ability of IVIM-MRI to differentiate patients with severe peripheral arterial disease (PAD) from normal subjects and evaluate the percutaneous transluminal angioplasty (PTA) results in patients with CLI.Methods:Eight patients who presented with CLI and six healthy volunteers were examined. The patients underwent IVIM-MRI of lower extremity before and following PTA. The imaging protocol included sagittal diffusion-weighted (DW) sequences. DW images were analyzed and color parametric maps of the micro-circulation of blood inside the capillary network (D*) were constructed. The studies were evaluated by two observers to define interobserver reproducibility.Results:Technical success was achieved in all patients (8/8). The mean ankle-brachial index increased from 0.35 ± 0.2 to 0.76 ± 0.25 (p < 0.05). Successful revascularization improved IVIM microperfusion. Mean D* increased from 279.88 ± 13.47 10⁻⁵ mm²/s to 331.51 ± 31 10⁻⁵ mm²/s, following PTA, p < 0.05. Moreover, PAD patients presented lower D* values as compared to healthy individuals (279.88 ± 13.47 10⁻⁵ mm²/s vs 332.47 ± 22.95 10⁻⁵ mm²/s, p < 0.05, respectively). Good interobserver agreement was obtained with an ICC = 0.84 (95% CI 0.64–0.93).Conclusions:IVIM-MRI can detect differences in microperfusion between patients with PAD and healthy individuals. Moreover, significant restitution of IVIM microperfusion is found following successful PTA.Advances in knowledge:IVIM-MRI is a safe, reproducible and effective modality for evaluation of lower limb hypoperfusion in patients with PAD. It seems also to be a helpful tool to detect changes of tissue perfusion in patients with CLI following revascularization.     

The role of cytokines in polymyositis

Objective. To investigate the effect of interferon-γ (IFNγ) on the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differentiation and maturation in vitro. Methods. Human muscle cell cultures were established from normal muscle biopsy material, using the explant technique. T cells were studied for their capacity to adhere to IFNγ-treated and untreated myoblasts and myotubes. The role of intercellular adhesion molecule type 1 (ICAM-1) in cell adhesion to muscle cells was examined in blocking studies, by enzyme-linked immuno-sorbent assay (ELISA), and by immunohistochemical staining using monoclonal antibodies (MAb). Results. Treatment of muscle cells (myoblasts and myotubes) with IFNγ resulted in a significant dose-dependent increase in the number of adherent T cells. Adhesion of T cells to muscle cells was significantly inhibited by MAb to ICAM-1 and to lymphocyte function–associated antigen type 1, but not by MAb to HLA–DR. There was no difference in the level of T cell adhesion to IFNγ-treated allogeneic versus autologous muscle cells. By ELISA and immunohistochemical analysis, ICAM-1 expression on the surface of cultured human muscle cells was either absent or barely detectable, but was strongly induced by treatment of muscle cells with IFNγ. Conclusion. Induction of cell adhesion molecules on muscle cells by IFNγ may be an important mechanism for the localization of T cells in the affected muscles of patients with autoimmune myositis.