Cardiovascular & Haematological Disorders - Drug Targets - Volume 20, Issue 2, 2020

Introduction: Severe ankle hemophilic arthropathy can be a calamitous sign of severe hemophilia with important inferences for activities of daily living. Aims: To summarize the contemporary, accessible information on Total Ankle Replacement (TAR) for ankle hemophilic arthropathy. Methods: A search of Cochrane Library and PubMed (MEDLINE) regarding the role of TAR in ankle hemophilic arthropathy. Results: The insufficient information regarding the results of TAR for hemophilic arthropathy is confined to scanty case series and case reports. An evaluation of the accessible literature reveals encouraging but inconstant outcomes. The reported rate of adverse events is 33%. The reported anticipated survival of TAR is 94% at 5 years, 85% at 10 years and 70% at 15 years. Conclusion: Whereas people with advanced hemophilic arthropathy of the ankle are prone to ameliorate pain and range of motion following TAR, there is deficient knowledge to regularly recommend its use. Adverse events and infection percentages are disturbing. Moreover, the lack of survival analysis knowledge makes it difficult to assess the benefit to people with hemophilia. TAR is a demanding surgical procedure and its survival is not comparable to that after hip or knee replacement.

Background: Statins are currently used for secondary prevention of Coronary Heart Disease (CHD), as the lipid-lowering therapy with them is proven safe and effective. Objective: The purpose of this research is to investigate the dose-dependent effect of statins used for secondary prevention of coronary heart disease, as well as mechanisms of quantitative and qualitative changes in lipoproteins, fatty acids and cholesterol in the blood and tissues of people of both sexes. Methods: In a clinical trial (n=125, of which 89 patients belong to group 1 and 36 to group 2) and an experiment on laboratory animals (n = 100), simvastatin reduced the total level of fatty acids in blood plasma, when given in the amount that was within the therapeutic dose range. Results: This effect was achieved through a drug-induced improvement in the capacity of hepatic cells to absorb Low-density (LDL) and Very-low-density (VLDL) lipoproteins. Conclusion: Considering the formation of saturated fatty acids, statin performed better in males. With Omega-3 polyunsaturated fatty acids involved, changes in lipoproteins, cholesterol and fatty acids (liver and myocardium) were similar to those caused by small doses of a statin drug. Effects of the combination of bisoprolol and acetylsalicylic acid were completely different from those caused by the use of statin.

Background: The effect of hydroalcoholic extract of Ziziphus jujuba (ZJ) on hypertension has been reported previously. Objective: This experiment investigates the effect of two ethyl acetate (EA, a polar and semi-polar compound) and aqueous fractions (AQ, a polar compound) of ZJ extract on cardiovascular parameters in acute hypertension induced by angiotensin II (AngII). Methods: Rats were randomly divided into following groups (n=7 in each group): 1) Control; 2) AngII (50 ng/kg); 3) Losartan (LOS, 30 mg/kg) + AngII; 4, 5) ethyl acetate fraction (EA150 and EA300 mg/kg) + AngII and 6, 7) aqueous fraction (AQ150 and AQ300 mg/kg) + AngII. Rats were treated with both fractions and LOS orally for four weeks and in the experiment day (28th) AngII intravenously injected and cardiovascular parameters (Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP) and Heart Rate (HR)) directly were recorded by a power lab system. Results: AngII could significantly increase SBP and MAP (P<0.001) and decrease HR with respect to the control and these responses were attenuated by LOS. The SBP and MAP in both doses of EA+ AngII and the higher dose of AQ fractions + AngII were significantly lower than the AngII group (P<0.05 to P<0.001). Bradycardia induced by AngII was also reduced by LOS and both fractions. The comparison of two fractions also showed that the effect of EA fraction is greater than the AQ. Conclusion: This study indicates that both fractions of the ZJ extract have a beneficial effect on hypertension. Because effect of EA was greater than AQ, we suggested that antihypertensive effects of ZJ mediated polar and nonpolar compounds.

Background: Inflammation has been shown to accompany Metabolic Syndrome (MetS) and its features. Cathepsin D is one of a proinflammatory mediator. In the current study, we aimed to investigate the effect of curcumin supplementation on serum cathepsin D levels in patients with MetS. Methods: The current study was conducted on 18-65 years old individuals with MetS diagnosed according to the International Diabetes Federation guidelines. A total of 80 participants were randomly divided into treatment and control groups. The first group (n=40) was given 2 capsules containing 500 mg of phosphatidylcholine complex of curcumin, and the other group (n=40) was given two 500 mg placebo capsules for 6 weeks. Before (week 0) and after (week 6) the intervention, anthropometric indices and blood pressure were measured and blood samples were taken. Serum cathepsin D was measured using an ELISA kit. Results: There was no significant difference between treatment and control groups in terms of weight, body mass index, waist circumference and serum cathepsin D levels before and after the intervention. In addition, there was no significant difference between pre- and post-trial values of serum cathepsin D. Conclusion: The present results do not suggest any effect of curcumin on cathepsin D levels in patients with MetS.

Background: Activation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV1) channels protects the heart from Ischemia/Reperfusion (I/R) injury through releasing Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP). The current study aimed to study the cardioprotective effects of TRPV1 in obesity. Methods: TRPV1 gene knockout (TRPV1-/-) and Wild-Type (WT) mice were Fed a High-Fat Diet (HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo. The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) and reperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 μmol/L) and SP (0.1 μmol/L). Then, Coronary Flow (CF), left ventricular peak positive dP/dt (+dP/dt), Left Ventricular Developed Pressure (LVDP) and Left Ventricular End-Diastolic Pressure (LVEDP) were measured. Results: HFD intake remarkably reduced CF, +dP/dt and LVDP and elevated LVEDP in both strains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt and LVDP, and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups. Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05). In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/- mice were improved by CGRP and SP. Conclusion: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced impairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/- mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.

Aims: Factor VIII (FVIII) replacement therapy remains a primary treatment for hemophilia A, however, the development of FVIII antibodies (inhibitors) and short half-life of the FVIII products are the major complications. Erythrocytes may prevent rapid removal of drugs from plasma. Erythrocytes are biocompatible and non-immunogenic drug delivery. In this study, in vitro activity of FVIII encapsulated by human erythrocytes was investigated. Methods: FVIII was loaded into erythrocytes using the hypo-osmotic dialysis technique. FVIII activity assay has been analyzed using Activated Partial Thromboplastin Time (APTT). Presence of FVIII on erythrocytes was detected by western blotting and flowcytometry using specific monoclonal antibody (abcam, U.K) against FVIII. Moreover, the osmotic fragility and hematologic parameters of FVIII-loaded carrier erythrocytes were measured. Results: Our results indicated that FVIII could not cross the membrane, where plenty of FVIII was found on the surface of the carrier erythrocyte. Flow cytometery results showed that 11% of the loaded carrier erythrocytes was positive for FVIII protein on their surface. The greatest activation of FVIII in both groups including lysate and non-lysate FVIII-loaded RBCs was observed on the first day, and the coagulant activity of this factor was gradually reduced on days 3 and 5. In 1:50 dilution of both groups, significant differences in FVIII activity were observed in 1:50 dilution of both groups, especially on the 5th day. Conclusion: This study aims to introduce erythrocytes as appropriate carriers for FVIII to prolong the dosing intervals in the effective and safe levels for a relatively longer time.

Background: Ursolic Acid (UA) is a pentacyclic triterpenoid carboxylic acid which is extracted from plants. UA may enhance the effect of Resistance Training (RT) in human. Objective: Current research was designed to show the effect of High-Intensity Resistance Training (HIRT) in the presence or absence of UA on the serum levels of irisin, CRP, IL-6 and TNF-α in the low activity men. Methods: The study included twenty-two healthy male HIRT with placebo, supplementation, and HIRT in the presence of UA supplementation. The two groups received eight-week intervention including 2 sets of 8 exercises, with 8~10 repetitions at 70~75% of 1 repetition maximum and a 2 min rest interval between sets, performed 3 times/week. Placebo or UA orally was evaluated as 1 capsule 3 times/day during 8 weeks. The subsequent factors were measured post- and preintervention: C-Reactive Protein (CRP), Irisin, Tumor Necrotic Factor (TNF-α) and Interleukin-6 (IL-6). Results: UA supplementation significantly increased the plasma levels of irisin in the HIRT+UA group versus the HIRT+P group (p<0.05). UA treatment also dramatically decreased the plasma levels of CRP, IL-6, and TNF-α in the HIRT+UA group versus the HIRT+P group (p<0.05). Conclusion: The current data showed that UA-induced an increase in serum irisin and reduction of CRP, IL-6, and TNF-α may have beneficial effects as a chemical for increasing of the effects of HIRT in low activity men.

Background: Laboratory data suggest that acute myeloid leukemia AML originates from a rare population of cells, termed Leukemic Stem Cells (LSCs) or leukemia-initiating cells, which are capable of self-renewal, proliferation and differentiation into malignant blasts. There is a universal agreement that LSCs lie within the CD34+ compartment of hemopoietic cells and most of leukemic stem cells express the interleukin-3 alpha chain receptor, CD123 and lack CD38. This study aimed to estimate the expression of LSC phenotype in AML patients and to correlate it with response to induction therapy. Methods: A cohort of 41 patients older than 15 years with newly diagnosed de novo AML were enrolled in this study. They were obtained from the National center of hematology in Baghdad and Baghdad teaching hospital between February and July 2013. The expression of CD34, CD38 and CD123 was assessed by multi-color flow cytometry. LSC positive (LSC+) samples must express CD34 and CD123 and lack the expression of CD38 in >1% of cells. French American British (FAB) classification system was used in this study. After four weeks of induction therapy; three groups were found: those who reached the Complete morphological Remission (CR), those who failed to reach CR and those who died before the assessment of morphological remission. The last two groups were merged for statistical purposes. Results: After the course of induction therapy, 41.46% of patients had complete morphological remission while 58.54% of the studied patients failed to reach complete remission. The Complete Remission (CR) rate was higher (53.33%) in patients who were negative for LSC phenotype than patients who were positive for LSC phenotype (34.61%). Conclusion: LSCs were expressed in 63.41% of AML cases and were in approximate distribution in FAB M3 and non-M3 patients. The expression of LSC phenotype was associated with poor response to induction therapy in AML patients.

Background: Ammodaucus leucotrichus (Apiaceae) is a medicinal plant widely used by the Moroccan population to treat various diseases including diabetes. Aims: The aim of this study was to evaluate the antidiabetic effect of the aqueous extract prepared from the fruits of this medicinal plant. Normal and streptozotocin-induced diabetic rats were treated orally by the extract of Ammodaucus leucotrichus (A. leucotrichus) at a dose of 10 mg/kg. Methods: The blood glucose levels were determined during 6 hours and 15 days during this treatment. In addition the oral glucose tolerance test as well as the analysis of histopathological changes of liver was performed. The antioxidant activity of aqueous A. Leucotrichus extract was also valuated by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH). Results: A. Leucotrichus fruit aqueous extract (ALFAE) reduced the blood glucose levels in both normal and diabetic rats. In addition, a remarkable influence on glucose tolerance was also noticed after ALFAE treatment. Moreover, ALFAE was able to exhibit a beneficial effect on histologlogical structure of liver. Finally a potential antioxidant effect has been shown in vitro. Conclusion: In conclusion, this study demonstrates the antihyperglycemic and hypoglycemic effects of A. Leucotrichus in rats supporting then its traditional use for the management of diabetes.

Background: The coexistence of two or more types of lymphoma within the same organ at the same time of diagnosis is defined as composite lymphoma, a rare disease that has recently been identified in the literature. Pointedly, the concurrence may be Hodgkin lymphoma with a Non-Hodgkin lymphoma [NHL], either B or T cells, or two different entities of NHLs. Furthermore, this condition has been described concurrently or sequentially. In order for the diagnosis to be established, two or more distinct clones should be proven by morphological and laboratory tests. Case Presentation: Herein, we cite a seventy-three-year old female patient with low-grade fever, waxing and waning cervical lymphadenopathy, whose biopsy of an axillary lymph node demonstrated the rare coexistence of Hodgkin and NHL, known as composite lymphoma. Conclusion: Composite lymphomas pose a particular diagnostic challenge, and currently, there are no agreed standards for treatment.

Background: Pure Red Cell Aplasia (PRCA) is a clinical entity comprising severe normochromic normocytic anemia, reticulocytopenia, erythroblastopenia in the bone marrow, with normal leukocyte and platelets count. PRCA can be classified into congenital and acquired, with the latter characterized as idiopathic or secondary to various infections, hematological malignancies, collagen vascular diseases, thymoma, and exposure to a variety of drugs and other chemical substances. Methods: Herein, we present a female patient, who presented with PRCA due to azathioprine treatment. Results: Prompt discontinuation of the drug together with red blood cells transfusions led to complete recovery in this young patient, without any addition of immunosuppressive regimen. Conclusion: We followed ‘the wait and see practice’ instead of administering immunosuppression to our patient, after careful consideration and extensive consultation with our hematologists. This ‘wait and see practice’ proved to be effective in the long run.