Structural and Binding Studies of SAP-1 Protein With Heparin

SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (K_D = 158 nm ). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity.     

Long-term albumin infusion in decompensated cirrhosis: A review of current literature

Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory dysfunction. Albumin infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis, large-volume paracentesis and hepatorenal syndrome. Emerging data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis patients. We review the current literature on both the established and potential role of albumin, and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.     

Ventricular asystole in a CRT‐D device. What is the mechanism?

We present a case of an 89‐year‐old man with a left ventricular assist device and cardiac resynchronization therapy device (CRT‐D) who presented with multiple presyncopal events. On the night of admission, telemetry revealed a 13‐s pause with appropriately timed pacing spikes but with failure to capture, followed by intermittent ventricular contraction with different QRS morphology. What was the mechanism for his ventricular asystole?     

Crystal storing histiocytosis: a rare presentation of plasma cell myeloma

Crystal storing histiocytosis (CSH) is a very rare association with plasma cell dyscrasias. It is presumed to be an intra-lysosomal accumulation of the secreted paraprotein aggregated into crystals and is associated with presence of variable numbers of histiocyte-like cells with phagocytosed crystalline inclusions in the bone marrow and other extramedullary sites Herein we report a case of multiple myeloma associated with CSH with a rapidly downhill clinical course. There was diagnostic confusion at the outset with a histiocytic disorder which was clarified with the use of Immunohistiochemistry along with serum protein electrophoresis and immunofixation.     

Thrombin‐Induced Platelet‐Fibrin Clot Strength Identified by Thrombelastography

Background and Objective

In‐stent restenosis (ISR) is a limitation of percutaneous coronary intervention and has been linked to specific clinical and angiographic variables. We aimed to simultaneously assess thrombosis biomarkers and lipid levels in patients with and without ISR.

Methods

Consecutive patients (n = 170) with a history of coronary stenting undergoing elective angiography were studied. Blood samples for thrombelastography, light transmittance aggregometry, and lipid levels were obtained prior to cardiac catheterization.

Results

Sixty‐nine patients (41%) had ISR (>50% luminal diameter stenosis). Among patients with ISR, 40 (58%) had ISR in more than one stent bed. Patients with ISR were more often female (37.7% vs. 21.8%, P = 0.04), had higher thrombin‐induced platelet‐fibrin clot strength (TIP‐FCS) (69.9 mm vs. 65.6 mm, P < 0.001), and a higher ApoB/A1 ratio (0.65 vs. 0.59, P = 0.03). In patients on dual antiplatelet therapy (n = 86), there were no differences in ADP‐, arachidonic acid‐, and collagen‐induced platelet aggregation between groups. The frequency of patients with ISR increased with TIP‐FCS quartiles and by ROC analysis, TIP‐FCS = 67.0 mm was the cutpoint for identification of ISR (AUC = 0.80 (95%CI 0.73–0.87, P < 0.0001). By multivariate analysis, TIP‐FCS ≥67.0 mm strongly associated with ISR (OR = 7.3, P = 0.004).

Conclusion

Patients with ISR identified at the time of cardiac catheterization have a prothrombotic phenotype indicated by high TIP‐FCS, a novel marker. Studies to confirm the prognostic utility of high TIP‐FCS for the development of ISR are ongoing. (J Interven Cardiol 2016;29:168–178)

     

β-Thromboglobulin, Platelet Production Time and Platelet Function in Vascular Disease

Plasma beta-thromboglobulin (beta TG) levels were measured in 103 healthy controls and 112 patients suffering from either peripheral vascular disease (PVD), or cerebrovascular disease (CVD) or deep vein thrombosis (DVT). Plasma beta TG was significantly elevated in 46 PVD patients and 24 recent DVT patients compared to controls, but did not differ significantly in 18 chronic DVT and 24 old CVD patients. In addition, heparin neutralizing activity (HNA) and platelet aggregation induced by adenosine diphosphate, 1-epinephrine and thrombin were compared in 33 out of the 46 PVD patients to 33 controls. The mean HNA was significantly shorter in the PVD patients than in controls. The rate and extent of platelet aggregation were increased in PVD patients compared to controls, but the difference was not statistically significant. Platelet production time (PPT) was measured in 20 controls, 35 PVD patients, nine chronic DVT and 12 chronic CVD patients; significantly shorter PPT was only observed in 14 patients with advanced PVD compared to controls, suggesting increased platelet consumption in these patients. All four assays (plasma beta TG, HNA, platelet aggregation and PPT) were performed in 25 patients; no correlation between the four tests was found in these patients suggesting that the tests were measuring various aspects of platelet function. These results suggest that in vivo platelet consumption as well as platelet aggregation and 'release reaction' are presumably enhanced in PVD and recent DVT patients and that plasma beta TG and PPT assays may be better and more specific indicators of in vivo platelet activation than in vitro platelet aggregation test.     

Assessment of mouth-to-mask ventilation in resuscitation of asphyxic newborn babies. A pilot study

The aim of the study was to compare the effectiveness of mouth-to-mask ventilation (MM) in neonatal asphyxia with bag-and-mask ventilation (BM). A new mouth-to-mask infant resuscitation system was constructed. The study was performed in two university clinics with different resources. The KEM Hospital in Bombay was well equipped and neonatologists took part in all resuscitations; Muhimbili Medical Centre in Dar es Salaam was understaffed and had no physicians available at resuscitation. Therefore, different protocols had to be used. In Bombay, the study period was limited to 5 minutes. If needed, mask ventilation was then replaced by intubation. In Dar es Salaam, MM ventilation was continued for up to 10 minutes, the inspiratory pressure was adjusted to 30 cmH₂O and the ventilation was slow (8–10 breaths/min). In Bombay, 30 babies were allocated to the BM and 24 to the MM groups. In Dar es Salaam 56 were in the BM and 64 in the MM groups. The results for term babies in Bombay and both term and pre-term babies in Dar es Salaam showed no significant differences between the two groups of treatment, as determined by Apgar score 4 at 5 and 10 minutes, number of babies with their first gasp, heart rate >130 beats/min or pulse oximeter values above 75%, all at 5 minutes. An Apgar score 4 at 5 minutes was achieved in more than 75% of all infants, irrespective of treatment. The rates of early neonatal mortality and neonatal convulsions did not differ between the two methods of resuscitation. In Dar es Salaam, the low respiratory frequency used in both groups was associated with a slow increase in heart rate above 130 beats per min. This result indicates that further studies will be needed before such slow respiratory frequencies are used. We conclude that, if adequate training is provided and the respiratory frequency is kept within the normal range, MM ventilation is an alternative to assisted ventilation when no bag and mask is available. However, further studies are necessary, since this method has proved to be tiring and uncomfortable for the resuscitating health personnel.