Pathophysiology,Diagnosis, and Management of Coronary No-Reflow Phenomenon

Coronary no-reflow phenomenon is a lethal mechanism of ongoing myocardial injury, following successful revascularization of an infarct-related coronary artery. Incidence of this phenomenon is high following percutaneous intervention, and is associated with adverse in-hospital and long-term outcomes. Several mechanisms such as ischemia-reperfusion injury and distal microthromboembolism in genetically susceptible patients and those with preexisting endothelial dysfunction have been implicated. However, the exact mechanism in humans is still poorly understood. Several investigative and treatment strategies within and outside the cardiac catheterization laboratory have been proposed, but have not uniformly shown success in reducing mortality or in preventing adverse left ventricular remodeling resulting from this condition. The aim of this article is to provide a brief and concise review of the current understanding of the pathophysiology, clinical predictors, and investigations and management of coronary no-reflow phenomenon.     

Aortic Delamination—A Possible Precursor of Impending Catastrophe

Aortic diameter is a powerful predictor of adverse aortic events, such as aortic rupture or dissection, forming the basis of prophylactic surgical repair criteria. Limited evidence is available regarding the association of aortic wall thickness (AWT) with these adverse aortic events. We present the case and surgical video of a 73-year-old man with chest pain and an increased AWT, who underwent ascending aortic repair and deep hemiarch placement under deep hypothermic circulatory arrest. Surgical pathology demonstrated evidence of aortic delamination and medial separation, indicative of an impending dissection. The patient recovered uneventfully, and his chest pain ultimately resolved after open repair. In this patient, increased AWT was felt to be the precursor to a potential aortic catastrophe.     

Simian virus (SV) 40 like sequences in cell lines and tumour biopsies from Australian malignant mesotheliomas

Background : Simian virus (SV) 40 sequences have been found in some, but not all studies of mesotheliomas. This virus is known to cause tumours in rodents but its role in human oncogenesis remains controversial.
Aims : The aim of this study therefore was to determine whether SV40 is associated with the development of mesotheliomas in Australia. The absence of the virus or its gene products in tissue derived from mesotheliomas would detract from this possibility.
Methods : We used polymerase chain reaction from three pairs of primers to amplify different regions of the large T antigen from DNA from cell lines and cDNA from both cell lines and an independent set of tumour biopsies from patients with mesothelioma.
Results : We examined five human mesothelioma cell lines that were established in our laboratories. In addition, we examined several tumour biopsies from seven different patients. SV40 like sequences were present in all the cell lines and in at least one sample from each of the patients examined.
Conclusions : The large T antigen of SV40 or an SV40 like virus is expressed in Australian mesotheliomas and therefore could be aetiologically-associated with tumourigenesis. Alternatively, these sequences could be expressed subsequent to the development of the disease.     

Averting transmission: A pivotal target to manage amoebiasis

Amoebiasis is a parasitic infectious disease caused by the enteric protozoan Entamoeba histolytica, a leading basis of deaths accounted to parasites, succeeding malaria and schistosomiasis. Conventional treatment methodologies used to deal with amoebiasis mainly rely on the administration of anti‐amoebic compounds and vaccines but are often linked with substantial side‐effects on the patient. Besides, cases of development of drug resistance in protozoans have been recorded, contributing further to the reduction in the efficiency of the treatment. Loopholes in the efficacious management of the disease call for the development of novel methodologies to manage amoebiasis. A way to achieve this is by targeting the essential metabolic processes of ‘encystation’ and ‘excystation’, and the associated biomolecules, thus interrupting the biphasic life cycle of the parasite. Technologies like the CRISPR‐Cas9 system can efficiently be exploited to discover novel and essential molecules that regulate the protozoan's metabolism, while efficiently manipulating and managing the known drug targets, leading to an effective halt and forestall to the enteric infection. This review presents a perspective on these essential metabolic processes and the associated molecules that can be targeted efficaciously to prevent the transmission of amoebiasis, thus managing the disease and proving to be a fruitful endeavour.     

Proteolytic activity of Plasmodium falciparum subtilisin-like protease 3 on parasite profilin,a multifunctional protein

Subtilisin-like proteases of malaria parasite Plasmodium falciparum (PfSUB1, 2 and 3) are expressed at late asexual blood stages. PfSUB1 and 2 are considered important drug targets due to their essentiality for parasite blood stages and role in merozoite egress and invasion of erythrocytes. We have earlier shown the in vitro serine protease activity of PfSUB3 and its localization at asexual blood stages. In this study, we attempted to identify the biological substrate(s) of PfSUB3 and found parasite profilin (PfPRF) as a substrate of the protease. Eukaryotic profilins are multifunctional proteins with primary role in regulation of actin filament assembly. PfPRF possesses biochemical features of eukaryotic profilins and its rodent ortholog is essential in blood stages. Profilin from related apicomplexan parasite Toxoplasma gondii (TgPRF) is known to be involved in parasite motility, host cell invasion, active egress from host cell, immune evasion and virulence in mice. In this study, mature PfSUB3 proteolysed recombinant PfPRF in a dose-dependent manner in in vitro assays. Recombinant PfPRF was assessed for its proinflammatory activity and found to induce high level of TNF-α and low but significant level of IL-12 from mouse bone marrow-derived dendritic cells. Proteolysis of PfPRF by PfSUB3 is suggestive of the probable role of the protease in the processes of motility, virulence and immune evasion.     

The effect of parity on placental weight and birth weight: Interaction with placental alkaline phosphatase polymorphism

The effect of parity on placental weight and birth weight is examined through a series of birth records from an Indian population in Calcutta. Placental weight and birth weight increase with parity, the maximum increment occurring between parities 1 and 2. This is compatible with a hypothesis of sensitization of the mother to foetal, paternally derived, antigens.

The three common placental alkaline phosphatase enzymic genotypes have no effect on determining foetal development.