Metformin therapy in COVID-19: inhibition of NETosis

Journal of Thrombosis and Thrombolysis -     

Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.     

An assessment of cerebral venous thrombosis risk factors and associated clinical outcomes in Jazan region,Saudi Arabia

Objectives:To assess cerebral venous thrombosis risk factors, and associated clinical outcomes in Jazan region, Kingdom of Saudi Arabia.Methods:This study is a retrospective review of the medical records of patients diagnosed with cerebral venous thrombosis and admitted to King Fahad Central Hospital in Jazan between 2010 and 2019. Data concerning socio-demographics, clinical features, risk factors, laboratory, and imaging investigations were retrieved. Furthermore, data about cases management, and outcomes, including death, were collected and analysed.Results:A total of 51 medical records were identified. The majority of the patients were females (68.6%), and the mean age of the patients was 33.3 years, of which three patients were under 18 years old. The most frequently recorded symptom was headache (76.5%), followed by seizure (45.1%). The most commonly recorded risk factor was protein S deficiency (57%), followed by anaemia (51%). Venous infarction and haemorrhage were the most common acute complications (13.7%). The majority of the patients had a favourable prognosis where only 27.5% recovered with disability and only one patient died due to the disease.Conclusion:Clinical presentation of cerebral venous thrombosis in Jazan region is similar to other local and international studies. However, anaemia was recorded as a main risk factor for the disease, which might require further investigation to assess the possible association between prevalence of anaemia in Jazan region and the incidence of cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease in comparison with arterial stroke. CVT cases represent approximately 0.5-1% of all types of stroke which mainly occur in young and middle-aged adults.1 The data concerning the global epidemiology of CVT is currently limited.2 However, the incidence of CVT has been reported to vary between countries where the incidence might be higher as in Asian and the Middle Eastern countries in comparison to Australia and European countries.3According to a recent study conducted in Australia, the incidence of CVT was reported to reach 15.7 per 1,000,000 persons on a yearly basis. The incidence was higher among women and among those between 31-50 years old.4 In the Middle East, an Iranian study looked at the frequency of CVT between 2001 and 2004, and the annual frequency of CVT was 12.3 per one million.5 An older study, conducted in the city of Riyadh in Saudi Arabia between 1985 and 1994, identified 40 cases of CVT. Those identified were aged between 16 and 40.6 In addition, in a more recent study conducted in Jeddah and Al-Baha between 1990 and 2010, the number of detected cases of CVT was 111 where 19 of these were detected among children.7The CVT occurs when a thrombus develops as a result of a disturbance of the balance between the process of prothrombosis and thrombolysis.8,9 Risk factors for CVT can be categorised into transient and permanent risk factors. Permanent risk factors are hereditary thrombophilia, systemic diseases or miscellaneous factors, such as obesity. Transient risk factors can be subcategorised into sex-specific, iatrogenic, or miscellaneous risk factors, such as infection, head trauma or anaemia.8 The prevalence of CVT risk factors differs between countries. Infection, pregnancy, post-partum period, and dehydration have been reported to be more common in Asia and the Middle Eastern countries in comparison to European countries.8Patients with CVT exhibit variable clinical manifestations and complications, some of which can be life threatening. The most common clinical presentation is a headache, while some patients exhibit other signs and symptoms, such as seizure, decreased level of consciousness, vomiting, focal neurological deficit, or visual symptoms.8-10 Venous infarction and haemorrhage are frequently reported complications of CVT.11 Late presentation of CVT patients can increase the risk of disability and death. The mortality rate among CVT patients has been reported to vary between 4.3% and 6.8%.12Since CVT risk factors and vulnerable groups can vary between different populations, assessment of the distribution of risk factors among local populations can be clinically valuable. Studies assessing CVT prevalence and associated risk factors and clinical outcomes in Saudi populations are currently limited. Furthermore, data about CVT in Jazan region is currently lacking. This investigation aims to identify cases diagnosed with CVT in Jazan region and to evaluate the risk factors and associated clinical outcomes.     

Metabolic reprogramming in childhood acute lymphoblastic leukemia

The first observations of altered metabolism in malignant cells were made nearly 100 years ago and therapeutic strategies targeting cell metabolism have been in clinical use for several decades.  In this review, we summarize our current understanding of cell metabolism dysregulation in childhood acute lymphoblastic leukemia (cALL). Reprogramming of cellular bioenergetic processes can be expected in the three distinct stages of cALL: at diagnosis, during standard chemotherapy, and in cases of relapse. Upregulation of glycolysis, dependency on anaplerotic energy sources, and activation of the electron transport chain have all been observed in cALL. While the current treatment strategies are tackling some of these aberrations, cALL cells are likely to be able to rewire their metabolism in order to escape therapy, which may contribute to a refractory disease and relapse. Finally, here we focus on novel therapeutic approaches emerging from our evolving understanding of the alterations of different metabolic networks in lymphoblasts.     

The effect of nadroparine on coagulation mechanisms: ultrastructural analysis.

Low molecular weight heparins are widely used in the prophylaxis and treatment of thrombotic disorders. The effect of low molecular weight heparins on coagulation was examined ultrastructurally in an animal model. A test and a control group was formed, each consisting of five rabbits. Nadroparine (225 Institute of Chaoy Unit/kg twice daily) was applied to the test group for 10 days. The control group received 1 ml saline solution subcutaneously. Blood and vascular tissue samples collected at the end of the 10th day were evaluated under a JEM 100 B electron microscope. Platelet degranulation and agglutination was observed in the control group. Fibrin materials were detected in the cytoplasms and surroundings of degranulated platelets. Erythrocyte accumulation was remarkable on the vascular endothelium with intact coagulation periods. In the test group, outer membranes of platelets, hyalomere, and granular structures in the granulomeres were detected to be nearly intact. There were rare erythrocytes in the large vascular lumens. The aggregation phase had occurred but no agglutination was detected. Nadroparine seems to preserve consistency of lipoprotein membranes of platelets and granular structures containing enzymes, which contribute to the coagulation mechanisms.     

Localization of Apaf1 gene expression in the early development of the mouse by means of in situ reverse transcriptase-polymerase chain reaction.

Apoptosis is an essential ubiquitous process that controls the duration of the life span of cells, thus playing a crucial role in morphogenetic, histogenetic, and phylogenetic developmental processes. Apaf1 (apoptosis protease activating factor 1) is one of the central mediators of the intrinsic apoptotic pathway and a part of the apoptosome, which activates procaspase-3 and promotes cell death. Gene knockout of Apaf1 in mice leads to late embryonic lethality with malformations such as the persistence of interdigital webs and hyperplasia of brain and retina. Therefore, Apaf1 is generally believed to play a crucial role in developmental apoptosis and have a widespread expression. However, its pattern of expression in early development remains unknown. To specify whether Apaf1 indeed plays this key role, we investigated the pattern of gene expression for Apaf1 in mouse embryos on day 7, 9, and 12 of development. Our results show, that gene expression for Apaf1 first occurs within the embryo between day 7 and 9 of development, becoming more widespread toward day 12 and then includes structures, such as yolk sac, mesenchyme, cartilage, heart anlage, otic vesicle, peridermis, and anlagen of the spinal ganglia and vertebral bodies. Our results also show that gene expression for Apaf1 is not ubiquitous in early mouse development. This finding indicates that cell death processes are independent of or less dependent on Apaf1 during this time. Of interest, an active gene expression for Apaf1 is also present in organ anlagen such as heart or intestine, in which no obvious phenotype is seen after Apaf1 deletion. This finding suggests a possible role for Apaf1 in such anlagen as a putative alternative compensatory pathway, which could be switched on in the case of defects in the mediators that are normally involved in such organs.