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.     

Evolutionary puzzle of Toxoplasma gondii with suicidal ideation and suicide attempts: An updated systematic review and meta‐analysis

The World Health Organization has reported an annual global suicide rate of 14.5 per 100,000 people. On the other hand, it is estimated that approximately one‐third of the global population are infected with Toxoplasma gondii (T. gondii) parasite. It is widely assumed that microbial pathogens, such as T. gondii, are probably associated with affective and behavioural modulation. The present article aimed to assess the proposed role of toxoplasmosis in raising the risk of suicidal ideation (SI) and suicide attempts (SA) using the available epidemiological data. Seven major electronic databases and the Internet search engine Google were searched for all the studies published between the 1st of January 1950 and 31st of October 2019. The heterogeneity and the risk of bias within and across studies were assessed. Following data extraction, pooled odds ratios (ORs) with 95% confidence interval (CI) across studies were calculated using the random‐effects models. A total number of 9,696 articles were screened and 27 studies were regarded as eligible in our systematic review (SI with five papers and 22 papers on SA). A significant association was detected between antibodies against T. gondii with TA (ORs = 1.57; 95% confidence interval [CI] 1.23–2.00, p = .000). Exploration of the association between T. gondii and SA yielded a positive effect of seropositivity for IgG antibodies but not IgM. Despite the limited number of studies, a statistical association was detected between suicidal behaviours and infection with latent T. gondii.     

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.