Prophylactic Impact of Beta vulgaris L in Ameliorating Cyclosporine A-Induced Hepatotoxicity in Rats

Background: Hepatotoxicity induced by Cyclosporine A (CsA) remains one of the major side effects. The aim of this studywas to determine the protective effects of beet root (Beta Vulgaris L) extract and silymarin against hepatotoxicity induced byCyclosporine A in rats. Methods: Sixty male albino rats, were divided into 6 groups (n=10). Group I control group. GroupII CsA-treated and received (50mg/kg weight, orally). Group III received (500mg/kg b.wt) beet root extract orally. Group IVreceived beet root extract and CsA as in group II and III. Group V was received (100 mg/kg b.wt) silymarin orally. Group VIreceived CsA and silymarin as in group II and V. Serum levels of (ALT, AST, ALP) and bilirubin (Total and Direct) weremeasured. Oxidative stress biomarkers, antioxidant status, damage to DNA, apoptosis and inflammatory mediators weremeasured in the tissues of the liver. Result: CsA administration significantly increased serum levels of the liver enzymesALT, AST, ALP and bilirubin. In addition, significant increase in MDA, Nitrite, 8-OHdG, caspase3, NF-κB, TNF-α andsignificant decrease of GST in liver tissues was noticed. Furthermore, histopathological changes occurred in CsA treatedrats exhibited disruption of normal liver architecture, congested central vein, vacuolated cytoplasm and inflammatory cellsinfiltration. Co-administration of beet root extract or silymarin +CsA ameliorated all these parameters. Conclusion: Thepresent study suggests that beet root extract and silymarin have beneficial effect in reducing hepatotoxicity induced by CsAvia decreasing oxidative stress, inflammation, DNA damage, apoptosis and repairing the histopathological changes.

Assessment of The Potential Role of Parsley (Petroselinum Crispum) Leaves Extract in Ameliorating Cyclosporin A- Induced Nephrotoxicity in Rats

In this study, a potentiometric titration method by Calvin-Bjerrum and Irwing-Rosotti was used to investigate binarycomplexes of ibandronate sodium, a nitrogen-containing bisphosphonate, with Ca(II), Mg(II) and Sr(II). Dissociationconstants (pKa) of ibandronate sodium were measured and the stability constants of the complexes formed in aqueoussolutions at 22 oC (I = 0.11 M NaClO4) were determined. The stoichiometry of ibandronate sodium/metal complexes wasfound as 1/1 for each metal ion.

Prophylactic Impact of Beta vulgaris L in Ameliorating Cyclosporine AInduced Hepatotoxicity in Rats

Background: Hepatotoxicity induced by Cyclosporine A (CsA) remains one of the major side effects. The aim of this studywas to determine the protective effects of beet root (Beta Vulgaris L) extract and silymarin against hepatotoxicity induced byCyclosporine A in rats. Methods: Sixty male albino rats, were divided into 6 groups (n=10). Group I control group. GroupII CsA-treated and received (50mg/kg weight, orally). Group III received (500mg/kg b.wt) beet root extract orally. Group IVreceived beet root extract and CsA as in group II and III. Group V was received (100 mg/kg b.wt) silymarin orally. Group VIreceived CsA and silymarin as in group II and V. Serum levels of (ALT, AST, ALP) and bilirubin (Total and Direct) weremeasured. Oxidative stress biomarkers, antioxidant status, damage to DNA, apoptosis and inflammatory mediators weremeasured in the tissues of the liver. Result: CsA administration significantly increased serum levels of the liver enzymesALT, AST, ALP and bilirubin. In addition, significant increase in MDA, Nitrite, 8-OHdG, caspase3, NF-κB, TNF-α andsignificant decrease of GST in liver tissues was noticed. Furthermore, histopathological changes occurred in CsA treatedrats exhibited disruption of normal liver architecture, congested central vein, vacuolated cytoplasm and inflammatory cellsinfiltration. Co-administration of beet root extract or silymarin +CsA ameliorated all these parameters. Conclusion: Thepresent study suggests that beet root extract and silymarin have beneficial effect in reducing hepatotoxicity induced by CsAvia decreasing oxidative stress, inflammation, DNA damage, apoptosis and repairing the histopathological changes

Antitumor effect of thymoquinone combined with resveratrol on mice transplanted with breast cancer

Objective To test the anticancer potential activity of the combination of thymoquinone (TQ) and resveratrol (RES) against breast cancer in mice. Methods The antiproliferative activity of TQ, RES and their combination was assessed against three breast cancer cell lines and one normal cells using MTT assay. The combination index was calculated using isobolographic method. Balb/C mice were inoculated with EMT6/P cells and in vivo antitumor activity was evaluated. Results The combination therapy also caused significant decrease in tumor size with a percentage cure of 60%. The combination therapy induced geographic necrosis, enhanced apoptosis, and decreased VEGF expression. Serum levels of IFN-γ were elevated in mice treated with combination therapy with no liver or kidney toxicity. Conclusions The combination of TQ and RES against breast cancer in mice can work synergistically. The anticancer effect of this combination is mediated by apoptosis induction, angiogenesis inhibition and immune modulation.

Antitumor effect of thymoquinone combined with resveratrol on mice transplanted with breast cancer

OBJECTIVE@#To test the anticancer potential activity of the combination of thymoquinone (TQ) and resveratrol (RES) against breast cancer in mice.@*METHODS@#The antiproliferative activity of TQ, RES and their combination was assessed against three breast cancer cell lines and one normal cells using MTT assay. The combination index was calculated using isobolographic method. Balb/C mice were inoculated with EMT6/P cells and in vivo antitumor activity was evaluated.@*RESULTS@#The combination therapy also caused significant decrease in tumor size with a percentage cure of 60%. The combination therapy induced geographic necrosis, enhanced apoptosis, and decreased VEGF expression. Serum levels of IFN-γ were elevated in mice treated with combination therapy with no liver or kidney toxicity.@*CONCLUSIONS@#The combination of TQ and RES against breast cancer in mice can work synergistically. The anticancer effect of this combination is mediated by apoptosis induction, angiogenesis inhibition and immune modulation.

Assessment of the Potential Role of Silymarin Alone or in Combination with Vitamin E and/ or Curcumin on the Carbon Tetrachloride Induced Liver Injury in Rat

ABSTRACT The aim of this study was to investigate the effective role of silymarin either alone or in a combination with vitamin E and/or curcumin against the toxic impact of carbon tetrachloride (CCl4) induced liver injury The results revealed that administration of silymarin alone or in a combination with vitamin E and/or curcumin for 21 consecutive days, 24 h after CCl4 injection to rats, markedly ameliorated DNA damaged and apoptosis markers in rat livers, proinflammatory markers including tumor necrosis factor- α (TNF- α) and C-reactive protein (CRP ) in rat livers as well as interleukin 6 (IL-6), interferon gamma (IFN-γ) and vascular endothelial growth factor (VEGF) in rat sera. These treatments also could ameliorated the alteration in cytochrome P450 2E1 (CYP2E1) activity in livers of CCl4 intoxicated rats as well as the increase in the serum alanine aminotransferase (ALT) compared with CCl4 intoxicated untreated rats. The present biochemical results are supported by histo-pathological examination. In conclusion, silymarin in a combination with vitamin E and curcumin was the most effective treatment in alleviating CCl4 induced liver damage and this may support the use of this combination as an effective treatment against liver damage induced by toxic agents.

Clinical pharmacist-led diabetes management and education program effect onthe Arabic-speaking people in Australia: a pilot study

The aim of the study was to examine the feasibility of pharmacist-led diabetes educational programme on diseasecontrol and health-related quality of life in Arabic-speaking Type 2 diabetes patients in Australia. Participants' HbA1cvalues improved over the three months period, decreasing from 8.86% to 8.34%, weight decreased from 84.78 kg to83.88 kg and diastolic blood pressure decreased from 75.40 mm Hg to 72.40 mm Hg. Mean waist circumference of theparticipants improved from average mean 107.40 cm to 105.88 cm. Goals included the following: quitting or reducingthe number of cigarettes per day, choosing healthy food, exercise, reducing weight, and monitoring glucose levels. Atthe end of the three months period, participants demonstrated clear achievements of goals set. For a feasibility study,the information gathered was valuable for developing future studies in this area. Results from this study indicate that apharmacist-led diabetes education addressing the spiritual, cultural, lifestyle and educational needs of Arabic speakingpeople with diabetes when successfully implemented has the potential to improve health related outcomes. Insummary, participants in this research did have clear improvements in clinical measures following the intervention

Diabetes mellitus revisited: a narrative review

To explore the management of diabetes from a pharmacy perspective and engaging patients in self-management

Methods: A search was made of international peer-reviewed literature in PubMed, Medline, Cochrane Library and thegrey literature. This document provides a review of a relevant literature including a general overview of diabetesmellitus, therapeutic goals, pharmacologic and lifestyle treatment. The epidemiology of diabetes was explored, and anoverview of new approaches for treatment and management of diabetes mellitus collated

Results: The search yieldedstudies and information that met the inclusion criteria. Pharmacological and lifestyle management, diabetes educationand knowledge, and the prevalence of diabetes were also documented

Conclusion: Research examining the role ofhealthcare providers as diabetes educators and exploring the needs of patients with diabetes is of importance tooptimize health outcomes and minimize costs related to treatment and complications

Clinico-Demographic Analysis and Outcome of Childhood Thrombosis in a Pediatric Hematology-Oncology Unit: A single Center Experience.

Aim of the study: Thrombosis is rare in childhood with limited studies. Our retrospective study was designed to evaluate children with documented thrombotic events registered in our pediatric hematology -oncology unit over the last 3 years as regards clinical features, etiology, management and outcomes. Methods: Among 963 newly registered, 30 patients (16 females and 14 males, median age 4.5 years) with clinical and radiological evidence of thrombosis were identified. Data collection included clinical presentation, identifiable risk factors, thrombophilia screening, radiologic investigations, treatment and outcome. Results: Age at first thrombotic event was higher for patients with secondary than primary etiology (p=0.018). In 66.7% of patients, there was at least one identified risk for thrombosis, and cancer chemotherapy was the most frequent etiology. Inherited thrombophilia were proven in 13.3%. Secondary thrombophilia presented mostly with neurological symptoms (70%) while inherited thrombophilias with purpura fulminans (80%) (p=0.001). The recurrence was higher with primary (30%) compared to secondary thrombophilias (10%). Patients' outcome included neurologic deficit (26.7%), recurrence (16.7%), amputation (6.7%) and death (16.7%). Conclusion: Thrombosis secondary to an acquired risk factor occurred at older age, commonly presented by central thrombosis with no significant difference between primary and secondary thrombosis in the residual effects. Further studies are warranted to determine proper duration of anticoagulant therapy to prevent recurrence.

Gene mutations in Wilson disease in Egyptian children: report on two novel mutations

Wilson disease [WD] is an autosomal recessive disorder, caused by defects in copper-transporting P-type adenosine triphosphatase [ATPase] encoded by the ATP7B gene, resulting in the deposition of copper in the liver and brain with significant disability or death if left untreated. An available regimen of treatment gives hope to those predisposed to the disease if diagnosed early. The objective of this study was to determine the frequency of the most common European mutation [p.H1069Q] in Egyptian children with WD, in addition to screening for previously reported mutations in the Egyptian patients in our selected group. Direct DNA sequencing was applied to exons [13, 14, 18, and 19] of the ATP7B gene for 19 patients previously diagnosed with WD. Then DNA sequencing and pedigree analysis were performed in the families of the patients showing variations in their results for the purpose of family screening and carrier detection. Six out of 19 patients were studied with their families [three families]. We identified five variants of which two were novel among the studied patients. One of the novel variants was synonymous substitution [p.A1074A] in 16% of patients and the other was predicted to be missense disease-causing mutations [p.T1076I] in 16% of patients, and three previously published mutations p.H1069Q were detected in 5% of patients, p.P1273Q in 10% of patients, and a silent variant p.A1003A in 26% of patients. Screening for the two exons 14 and 18 of the ATP7B gene is important in Egyptian patients especially in suspected patients without hepatic manifestations

Subjective assessment to an educational tool used for the Arabic population with diabetes in Australia

Despite a rapid growth of Type 2 diabetes in Arab Australians, the management of diabetes in this population is yet understudied. The first aim of this study is to participants' views about: taking medicines regularly, knowledge and feelings about diabetes, sources of medicines information, and special needs of being from an Arabic speaking background. The second aim is to explore participants' feedback about the use of the Diabetes Conversation Map as an educational tool in Arabic. Focus groups were conducted in Arabic-speaking Australians with Type 2 diabetes who were asked about their knowledge and self-care skills of diabetes as well as experience of living with the disease. Common themes emerged from the focus groups included knowledge, state of mind, and needs of the Arabic speaking population. The findings provide valuable information for research in this area by designing interventions that would be translated to clinical practice

Establishment of callus and cell suspension cultures of cassia bicapsularis L.

Callus cultures were initiated from leaf of Cassia bicapsularis L. on solid Murashige and Skoog [MS] basal medium supplemented with different growth regulators. Excellent growth of callus was obtained in medium supplemented with 1 mg/l 2, 4-dichlorophenoxyacetic acid [2, 4-D] and grown in the dark. The obtained callus was subcultured every 4 weeks in the dark at 25°C. The Callus was compact, yellowish brown in color and used for establishment of cell suspension cultures. Maximum growth of suspension cultures was achieved in medium supplemented with 1 mg/l 2, 4-D and 0.1 mg/l kinetin. The growth rate of cells was initially slow but as the cultures proceeded, the growth increased significantly over a period of 22 days then the growth of cells was stable for 35 days

Evaluation of cystatin capture ELISA and sodium metaperiodate antigen treated ELISA in diagnosis of toxoplasmosis

ELISA has become the mainstay for clinical serologic evaluation of toxoplasmosis. One of the major obstacles encountered in the evaluation of ELISA is the false-positive results due to immunological cross-reactions with other parasitic diseases that exhibit some lack of specificity. Evaluation of the diagnostic efficacy of two ELISA techniques: Cystatin capture ELISA and sodium metaperiodate treated antigen-ELISA [SMP-ELISA] compared to conventional ELISA, to detect IgG antibodies for crude T. gondii antigen in sera of toxoplasmosis patients. The study was carried out on 50 individuals categorized into three groups. Toxoplasmosis group included 30 patients confirmed by Sabin-Feldman dye test. Other parasitic diseases group included 10 sera from patients with amoebiasis [2], fascioliasis [2], hydatidosis [3] and schistosomiasis [3]. Control group included 10 healthy individuals. All sera under study were examined for the detection of T gondii IgG by three different ELISA techniques: Cystatin capture ELISA, SMP-ELISA amid conventional ELISA. The diagnostic performance of the three tests was statistically compared. Cystatin capture ELISA gave the best diagnostic results with 96.6% sensitivity, 95% specificity, 96.6% Positive Predictive Value [PPV], 95% Negative Predictive Value [NPV] and 96% diagnostic accuracy. In spite of the lower sensitivity and NPV of SMP-ELISA [86.6% and 82.6%, respectively] than the conventional ELISA, it had higher specificity [95%] and PPV [96.3%]. Cystatin capture ELISA improved the diagnostic performance of conventional ELISA in diagnosis of human toxoplasmosis

Pancreatic and chromosomal toxic effects of dimethoate in adult male albino rats

Dimethoate is an organophosphate insecticide with numerous uses in agricultural crops and ornamentals. The extensive use of dimethoate may pose a health hazard to animals and humans because of its persistence in soil and crops. This study was conducted to evaluate the pancreatic and chromosomal toxic effects of dimethoate in adult male albino rats. Sixty rats weighing 180-200gm were equally divided into 3 groups: group I [negative control], group II [positive control] and group III [dimethoate].The period of the study extended for 2 months, then 10 rats from each group were sacrificed for biochemical analysis [serum glucose, insulin, amylase and pseudocholinestrase] and pancreatic histopathology. The other 10 rats were used for chromosomal analysis. The results of this study showed no significant difference between the negative and positive control groups. However, there was significant difference in all measured biochemical parameters between the dimethoate and the negative control groups. The histopathological examination of pancreas revealed vacular degeneration in cells of the acini and 8- cells of islet's of langerhans with dark stained nuclei. Pancreatic acini showed loss of basal basophilia and acini architecture. Chromosomal analysis showed significant numerical aberration [hypoploidy] and increase in chromosomal structural aberrations [gaps, fragments, deletion and clumping]. It was concluded that dimethoate has pancreatic toxic effects and could cause chromosomal aberrations in adult albino rats

Comparative study of the role of D- pencillamine and garlic extract in treatment of lead poisoning in adult albino rats

Lead is one of the most useful materials in the world. The aim of this study was to compare the curative role of D-penicillamine and garlic extract in treatment of lead poisoning in adult albino rats. The study included 80 adult albino rats consisted of 7 groups. The period of lead intoxication extended for 3 months followed by either 1 month treatment [penicillamine or garlic extract] or 1 month of no treatment. Group I: consisted of 20 rats divided equally into the negative and positive control subgroups. Each of groups 11- VII consisted into 10 rats. Group [I: [P] Pencillamine alone in a dose of 25 mg/kg 6 days/ week for 1 month. Group III: [G] garlic extract alone in a dose of 20 mg/kg 6 days/ wk for I month. Group IV: [Pb] lead poisoning in a dose of 20 mg/kg 6 days/ wk for 3 months. Group V: [Pb-P] treatment with penicillamine in Pb poisoning. Group VI: [Pb-G] treatment with garlic extract in Pb poisoning. Group VII: [Pb-F] follow up of Pb poisoning without treatment. The results of this study revealed that lead poisoning significantly elevated blood lead level [BLL] and testicular lead level [TLL] when compared with the negative control rats. Lead was testicular toxicant as it produced atrophic germinal epithelium and arrested spermatogenesis. Treatment of Pb poisoning by penicillamine or garlic extract resulted in significant decrease in BLL and TLL with significant increase in urinary lead level [ULL] when compared with the Pb treated rats. Also, P and G treatment resulted in improvement of testicular structure. [n follow up group, BLL, ULL and TLL were significantly increased when compared with the negative control rats. Also, BLL was significantly decreased when compared with lead treated group. There was minimal improvement in testicular structure in Pb-F group. It was concluded that both penicillamine and garlic can treat lead poisoning. Moreover, garlic curative effect is better than that of penicillamine. garlic can be considered as a chelating agent in treatment of lead poisoning

Role of antioxidatns and supplementary therapy in cases of lead poisoning in Zagazig university hospitals

Lead is one of the most important elements that contribute to the impact on human health from many variable sources. It most commonly affects peoples living in developing countries where, chelating agents [main line of treatment] are not easily available. The aim of the present study was to evaluate the role of some antioxidants [garlic and silymarin] together with supplementary therapy in management of lead poisoned cases. This study was carried out in Zagazig University Hospitals in the period from January 2007 to December 2008. The study included 30 patients of both sexes and different ages, who presented as families with symptoms suggesting lead poisoning mainly abdominal colic and severe constipation. From the history they all share the same source of exposure, which was contaminated water from plumbed water pumps. The local health territory of Sharkia governorate was conveyed immediately after presentation of each family to take its procedures for water supply in the residence areas of the patients. After admission complete history taking, clinical examination and laboratory investigations; complete blood count [CBC], liver and kidney functions, blood lead level [BLL], glutathione [GSH] and malondialdehyde [MDA] levels and activity of superoxide dismutase [SOD] and catalase enzymes were analyzed for all patients at the time of admission and after 1, 2, 6 months of follow up and for control subjects. Treatment lines included garlic, silymarin, vitamins and minerals together with symptomatic treatment were given for 1 month at hospital and for another 1 month at home. All patients were from rural areas in Sharkia governorate. At admission all patients complained of abdominal colic and severe constipation. About 80% and 66.7% of cased complained of easy fatigability and body aches respectively. Blue line and pallor were found in 50% and 93.3% of cases respectively. Some of these symptoms and signs disappeared gradually after 1 and 2 months of treatment together with improvement of CBC, liver function, BLLs and antioxidant activity. While after 6 months of follow up all symptoms disappeared completely and most of measured parameters returned nearly to control values except BLLs were still elevated compared to control values. The present study revealed that lead induced deleterious effects may be due to oxidant stress and lipid peroxidation, as evidenced by significant drop in GSH level and decreased in activity of SOD and catalase enzymes, with increased serum level of oxidation product MDA. Moreover, these effects were ameliorated by treatment with antioxidants [garlic and silymarin] together with supplementation and symptomatic therapy. Also, recovery of antioxidant enzymes activity and GSH level with drop of MDA level was noticed after treatment. It is recommended to change the plumbed pipes of the water pumps, and to conduct further studies on larger number of populations to evaluate the effectiveness of garlic, silymarin and other antioxidants in treatment of lead poisoning

Possible protective role of L-carnitine on diclofenac induced hepatotoxicity in adult male albino rats [histological, immunohistochemical and biochemical study]

Diclofenac [DCLF] is in common use worldwide as non steroidal anti-inflamatory drugs [NSAIDs] that have been reported to cause significant adverse effects. L-Carnitine has been proposed as antioxidant because it helps reduce oxidative stress. This work aimed to study the possible histological, immunohistochemical and biochemical changes of liver associated with diclofenac administration and to assess possible beneficial role L- carnitine [LC] on diclofenac [DCLF] induced hepatotoxicity. Fifty adult male albino rats were divided into 4 main groups. Group I: Served as positive and negative controls. Group II: Received LC in a dose of 50 mg/ kg intramuscular [IM] in 1 ml saline. DCLF treated group [III]: Received DCLF 50 mg/ kg IM in 1 ml saline. Combined group [IV]: Rats received LC then DCLF after 2 hours IM. The treatments were given for the rats 6 days/ week for two weeks. At the time of sacrifice, the rats were anaesthetized; blood samples were taken for measuring liver function tests. Specimens from the liver of each rat were taken for light and electron microscopic examination. Histological examination of the liver of the rats of DCLF treated group revealed different degrees of focal lobular affection. Enlarged portal areas, congested portal and central veins, bile duct proliferation, cellular infiltration and fibrosis were detected. Significant decrease in area% of brown positive immunoreactions for glutathione peroxidase I [GPXI] was detected in comparison with control group. Necrosis of most of hepatocytes especially in those close to portal area was detected. Most of hepatocytes mitochondria appeared with ruptured membrane. Pretreatment with LC in combined group showed slight histological changes with sinusoidal congestion, minimal fibrosis around prominent portal area with significant increase in area% of GPX1 in comparison with DCLF treated group. Most of mitochondria appeared with intact membrane. There were significant elevations in liver function tests in DCLF treated group when compared with other groups with partial recovery in combined group. Results obtained in this study demonstrated that high doses of DCLF induced histological and biochemical changes in the liver due to oxidative stress and that the use of LC had partially reduced the DCLF induced toxicity. This may suggest that LC enhanced antioxidant defence and may be used as a cell protector for DCLF induced hepatotoxicity

Portal vein thrombosis and haematemesis in chronic liver disease. Are P-selectin and PSGL-1 clues?

Bleeding and thrombotic complications are common problems in patients with chronic liver disease [CLD]. The aim of the present study was to evaluate the level of soluble P [sP]-selectin, and P-selectin glycoprotein ligand-1 [PSGL-1] [CD162] expression on neutrophils among patients with CLD and to clarify the role of their interaction, by measuring the platelet leucocyte aggregates, on the clinical outcome of the haemostatic balance in those patients. We also investigated the hypothesis that the balance between platelet activation and endothelial biological function is impaired. sP-selectin and thrombomodulin [TM] levels were measured by enzyme-linked immunosorbent assay [ELISA] and flowcytometric detection of CD162 was performed. Platelet-leucocyte aggregation [PLA] in whole blood was measured as positive for CD41a and CD45 in 66 CLD patients divided into the portal vein thrombosis group [PVT] [n = 25], the haematemesis group [n = 21] and the haemostatically stable group [n = 20]. sP-selectin was significantly elevated in all patient groups. Decreased surface expression of CD162 on neutrophils was detected in all patients' groups. PLA was statistically significantly increased in the PVT group. TM was statistically significantly increased in the PVT, haematemesis and haemostatically stable groups. PLA may play a role in the unique PVT outcome of the haemostatic balance in a group of patients whose credentials of hyperdynamic portal circulation predispose them to bleeding rather than thrombosis. Consequently, P-selectin-targeted therapy may be used to prevent this complication

Cardiac events and cardiac T2[*] in Egyptian children and young adults with beta-thalassemia major taking deferoxamine

Cardiac events and death are not uncommon in adults with beta-thalassemia [beta-TM] taking deferoxamine [DFO] monotherapy because of poor compliance and possibly the less effectiveness of DFO in controlling cardiac iron overload. We sought to assess compliance with DFO, the percentage of shift to other iron chelators, and the occurrence of cardiac siderosis, and cardiac events and death in beta-TM patients on DFO monotherapy. Prospective, observational, 10-year follow-up of patients attending Ain Shams Thalassemia Unit, Cairo, Egypt. For all beta-TM patients aged 2-1 8 years attending the unit during January 1998 and taking DFO, we recorded all cardiac events [whether fatal or not] during January 2008. All patients still on DFO monotherapy and with a normal EKG and not showing symptoms or signs suggestive of heart failure [HF] were evaluated for cardiac siderosis byT2[*]. Of 412 patients, only 126 [31%] were still taking DFO monotherapy [only 43% of those were compliant], 136 were taking combined DFO and deferiprone [DFP], 72 were taking DFP and 32 were taking deferasirox [DFX]. Twenty-one were lost follow-up and 25 died [10 cardiac]. Eight of ten cardiac deaths and 12 of 15 non-cardiac deaths were in the DFO monotherapy group. Those taking DFO monotherapy with no HF and left ventricular ejection fraction [LVEF] by T2[*] >56% had a median age of 19 years and 56% were males; cardiac T2[*] was <20 ms in 30 [22%]; 10-20 ms in 20 [14.7%] and <10 ms in 10 [7.3%]. LVEF ranged from 58%-76% [median 64%]. Forty percent of T2* patients <10 ms were compliant with DFO. Fifty-eight percent of patients on DFO monotherapy were noncompliant, but even compliance did not prevent severe cardiac siderosis and most cardiac events [whether fatal or not] that occurred in the DFO monotherapy group

Evaluation and clinical correlation of bone marrow angiogensis and level of serum angiogenic factors in acute leukemia

In this study serum angiogenic factors vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF] and tumour necrosis factor a [TNF a]] and cellular angiogenic factors [VEOF and VEGF-R2] were studied in 50 newly diagnosed acute leukemia patients, they were 24 ALL and 26 AML patients. The correlations of the studied angiogenic factors to each other and to the patients' survival and disease outcome were studied. During the follow-up period of 6 months, 22 patients died and 28 patients remained alive from whom 11 patients were refractory and 17 patients achieved complete remission. On comparison between pretreatment concentration levels of measured serum angiogenic factors [VEOF, TNF-alpha and HOF] in ALL, AML and the control group, all the comparisons were statistically significant [p<0.0001, <0.0001 and 0.02 1 respectively]. All serum markers were higher in AML group than control group, but only VEOF showed statistically significant elevation [p<0.0001], while in ALL patients, all markers were significantly higher than control group [p=0.01]. When comparing ALL and AML cases according to cellular angiogenic factors detected by immunocytochemistry, cellular VEGF-R2 was slightly higher in ALL group, while cellular VEGF was slightly higher in AML group. The comparisons were statistically non-significant for both angiogenic factors. As regards response to therapy, in ALL, cases with high sVEGF showed a statistically significant lower rate of complete remission than cases with low sVEGF [p=0.041]. The same results were obtained for AML but the comparison did not reach a significant level [p=0.082]. Serum VEOF was the only reliable marker to predict relapse in ALL [p=0.009] and AML [p=0.049]. On comparing serum VEGF to the outcome in ALL, high sVEGF cases showed a statistically significant higher rate of death than low sVEGF cases [prO.05], while in AML, the same results were obtained but the comparison did not reach a significant level. As regards the survival time, cases with low sVEGF level showed higher mean survival and 6-month survival than cases with high sVEGF level p=0.03]. A significant negative correlation was detected between serum VEGF and serum TNF-a [correlation coefficient [r]=-0.642, p<0.0001]. Conclusion: Serum angiogenic factors [VEGF, TNF-alpha and HOF] are markedly increased in cases of acute leukemia compared to normal controls. Cases with high sVEGF showed higher rate of death than cases with low sVEGF, so its targeting may provide a potent novel therapeutic approach in acute leukemias. VEGF may also be useful as a new prognostic factor and a predictor of relapse in different types of acute leukemia. Further studies with larger number of patients and longer duration of follow-up are recommended to throw more light on the significance of other angiogenic factors in relation to acute leukemia