Cardiovascular & Haematological Disorders - Drug Targets - Volume 20, Issue 4, 2020

Prevention is essential for avoiding the complications of muscle hematomas (compartment syndrome, pseudotumors and peripheral nerve lesions) in hemophilic patients. This is achieved through early diagnosis of muscle hematomas and proper long-term hematological treatment until they have resolved (confirmed by image studies). Ultrasound-guided percutaneous drainage could be beneficial in terms of achieving better and faster symptom relief. Acute compartment syndrome (ACS) requires emergency surgical treatment (decompression fasciotomy). As for pseudotumors, the biopsy will help us confirm the diagnosis and rule out true tumors (chondrosarcoma, liposarcoma, synovial sarcoma) that sometimes mimic hemophilic pseudotumors. Surgical removal of hemophilic pseudotumors is the best solution. As alternatives, there are curettage and filling with cancellous bone and radiotherapy (when surgery is contraindicated). Preoperative arterial embolization (ideally 2 weeks before surgery) helps control intraoperative bleeding during surgery for giant pelvic pseudotumors. Peripheral nerve injuries, which are rare, almost always occur due to compression of hematomas in the vicinity. In most cases, they usually resolve with hematological treatment only. If such treatment fails, surgery would be indicated.

Cardiac arrhythmias are associated with several cardiac diseases and are prevalent in people with or without structural and valvular abnormalities. Ventricular arrhythmias (VA) can be life threating and their onset require immediate medical attention. Similarly, atrial fibrillation and flutter lead to stroke, heart failure and even death. Optimal treatment of VA is variable and depends on the medical condition associated with the rhythm disorder (which includes reversible causes such as myocardial ischemia or pro-arrhythmic drugs). While an implanted cardioverter defibrillator is often indicated in secondary prevention of VA. This review highlights the newest advancements in these techniques and management of ventricular and atrial tachyarrhythmias, along with pharmacological therapy.

Platelets are small blood cells known primarily for their ability to adhere and aggregate at injured vessels to arrest bleeding. However, when triggered under pathological conditions, the same adaptive mechanism of platelet adhesion and aggregation may cause thrombosis, a primary cause of heart attack and stroke. Over recent decades, research has made considerable progress in uncovering the intricate and dynamic interactions that regulate these processes. Integrins are heterodimeric cell surface receptors expressed on all metazoan cells that facilitate cell adhesion, movement, and signaling, to drive biological and pathological processes such as thrombosis and hemostasis. Recently, our group discovered that the plexin-semaphorin-integrin (PSI) domains of the integrin β subunits exert endogenous thiol isomerase activity derived from their two highly conserved CXXC active site motifs. Given the importance of redox reactions in integrin activation and its location in the knee region, this PSI domain activity may be critically involved in facilitating the interconversions between integrin conformations. Our monoclonal antibodies against the β 3 PSI domain inhibited its thiol isomerase activity and proportionally attenuated fibrinogen binding and platelet aggregation. Notably, these antibodies inhibited thrombosis without significantly impairing hemostasis or causing platelet clearance. In this review, we will update mechanisms of thrombosis and hemostasis, including platelet versatilities and immune-mediated thrombocytopenia, discuss critical contributions of the newly discovered PSI domain thiol isomerase activity, and its potential as a novel target for anti-thrombotic therapies and beyond.

The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement, including cardiac involvement. Even with the availability of advanced diagnostic testing and novel therapies, prognosis remains poor. It is overlooked as a cause of heart failure with preserved ejection fraction leading to a delay in diagnosis when management options are limited and associated with poor survival outcomes. Therefore, the education of physicians is needed to ensure that it would be highly considered as a differential diagnosis. The purpose of this manuscript is to review the advances in the diagnosis and management of cardiac amyloidosis with the aim of educating colleagues who provide care in the primary care setting. We have summarized the pathogenesis of amyloidosis, its association with plasma cell dyscrasias, novel diagnostic and surveillance approaches including echocardiography, cardiovascular magnetic resonance imaging, histopathologic techniques, systemic biomarkers, and advanced treatment approaches including supportive symptomatic management and standard of care chemotherapy targeting the amyloid deposits. Given the overall poor prognosis of amyloidosis, we have also discussed the role of palliative and hospice care.

Background: Evaluation of risk factors associated with coronary artery disease and cardiac health in hemophilia patients is necessary to prevent the onset of ischemic heart disease. In this study, we evaluated the cardiovascular status of hemophilic patients in Lorestan province for the early onset of ischemic heart disease. Methods: In this cross-sectional descriptive study, a total of 80 patients presenting severe hemophilia, a detailed questionnaire-based investigation was conducted to analyze the prevalence of cardiovascular risk factors in severe hemophilic patients. In patients with hemophilia, body mass index (BMI), blood pressure, diabetes, LDL, cholesterol and HDL, the risk of cardiovascular death was estimated using a predictive risk predictor algorithm of Europe SCORE. Results: The mean age of the patients was 25 years, where all the patients were non-diabetic. Echocardiography did not show any wall motion abnormality and changes in the T wave and dysrhythmia were also not seen by ECG. 7 patients had high blood pressure, 11 had abnormal HDL, and 1 had abnormal LDL. In this study, serum LDL and HDL levels were not significantly correlated with age and BMI. Conversely, age and BMI were significantly associated with hypertension. Hypertension was observed in people over the age of 25 years and in overweighed individuals. 78.8% had normal BMI and 21.3% were overweighed. There was no significant correlation between serum LDL, serum HDL, and blood pressure and sex. The levels of abnormal LDL and HDL were higher in men than in women. Conclusion: ECG findings from our study did not report any significant cardiac abnormalities among hemophilic patients. Cardiovascular risk factors were not significantly correlated in these patients.

Aims: To study the toxicological profile and anti-hyperlipidemic effects of Spondias mombin leaves methanolic extract in experimental rats. Background: Preventing high levels of lipids or its recurrence is currently one of the key aims of clinical and experimental studies. Objective: This study was carried out to investigate the toxicological profile and anti-hyperlipidemic effects of methanolic extract of leaves of Spondias mombin. Methods: The acute toxicity study was carried out where the limited dose of 2000 mg/kg body weight was administered to five rats at 48 h intervals. The interpretation was prepared and recorded for 24 h. In the sub-acute toxicity study, rats were treated with 250, 500, and 1000 mg/kg doses of the extract every 24 h for 28 days. The hematological, biochemical, and histopathological tests of treated animals were carried out at the end of the test. The anti-hyperlipidemic activity of plant extract (100, 200 mg/kg) was studied on Triton-X-100 induced hyperlipidemia in rats. Histopathological changes in the liver of rats were examined. Results: For acute and subacute treatment, the extract did not reveal any signs of toxicity or mortality, or any significant effects on hematological, biochemical parameters, and histopathology of organs. The extract demonstrated an important anti-hyperlipidemic result by decreasing the serum levels of cholesterol, TGs, LDL, VLDL, and enhancing HDL. Conclusion: Taking up the evidence of the experimental study, we can conclude that the methanolic extract of Spondias mombin leaves helps in declining hyperlipidemia in rats and it can be safely used for a period of 28 days to treat hyperlipidemia.

Aims: The study aimed to investigate the antihyperglycemic activity of Matricaria pubescens. Background: Matricaria pubescens (Def). Shultz (Asteraceae) is commonly used traditionally for the treatment of diabetes in Morocco. Objective: The present investigation aimed to assess the antihyperglycemic and antioxidant effects of the aqueous extract of the aerial part of Matricaria pubescens (M. pubescens). Methods: The effect of a single and repeated oral administration of the aqueous extract of aerial part of M. pubescens (AEAPMP) at a dose of 40 mg/kg on glucose was examined in normal and streptozotocin-induced diabetic rats. Additionally, histopathological examination of the pancreas and liver was carried out according to the Hematoxylin-Eosin method. The antioxidant activity was performed using the DPPH assay. Results: The results showed that the aqueous extract of M. pubescens (AEAPMP) exhibited a significant lowering activity on blood glucose levels in STZ-induced diabetic rats. In addition, AEAPMP ameliorated the histopathological tissues of the liver and pancreas. Furthermore, in vitro antioxidant activity of AEAPMP has been shown. Conclusion: In conclusion, this study demonstrates that M. pubescens possesses a beneficial effect against hyperglycemia associated with diabetes.

Aims: The aim of this study was to evaluate the antidiabetic effect of Scorzonera undulata. Background: Scorzonera undulata ssp deliciosa, locally known as “Guiz”, is used as a phytomedicine in Morocco and Algeria to treat different health problems. Interestingly, it is used in the Moroccan pharmacopeia to treat diabetes. To our knowledge, this medicinal herb has never been investigated for any pharmacological activity. Objective: This study aimed to evaluate the antihyperglycemic effect of the aqueous extract of the aerial part of Scorzonera undulata (SUAP) in normal and STZ-induced diabetic rats and to assess the acute toxicity of this extract in Wistar rats. Methods: This study investigated the effects of SUAP at a dose of 20 mg/kg on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rats. The acute toxicity of SUAP was examined according to the OECD test guideline; rats were divided into four groups of each sex and orally received the SUAP (1000, 2000, or 3000 mg/kg BW). Post-treatment, body weight, signs of toxicity, and/or mortality were observed during 14 days. Other assays such as histopathological examination, preliminary phytochemical investigation, determination of glycogen content and evaluation of α-amylase were performed according to standard protocols. Results: The findings of the current study depicted that both single and repeated oral administration of SUAP (20 mg/kg) generated a significant fall in the blood glucose levels in diabetic rats. A single oral administration of SUAP (at the highest dose of 3000 mg/kg BW) had no significant acute toxicological effects, and oral LD50 of SUAP was greater than 3000 mg/kg. Furthermore, repeated oral administration of SUAP during 15 days led to an increase in the liver glycogen content in diabetic rats to improve the histopathological structure of the liver and pancreas in SUAPtreated diabetic rats and to ameliorate some biochemical parameters such as ALT and creatinine. SUAP had no effect on α-amylase activity. In addition, the preliminary phytochemical investigation showed the richness of the roots of SUAP in some phytochemicals, particularly the polyphenols. Conclusion: The present study demonstrates the antihyperglycemic effect of Scorzonera undulata in diabetic rats which could be involved through the improvement of liver structure and function. In addition, the dose used is not toxic. Finally, the extract contains large amounts of bioactive compounds, mainly polyphenols.