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Gehad Hamed,1 Hisham M Omar,1 Abbas M Sarhan,2 Hossam E Salah1 1Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Al-Sharkia, Egypt; 2Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Zagazig University, Zagazig, Al-Sharkia, EgyptCorrespondence: Gehad Hamed, Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Al-Sharkia, 44519, Egypt, Tel +201092034529, Email gehadmahmodhamed@gmail.comPurpose: This study aimed to assess PIM-2 gene expression level as a prognostic marker in AML patients and to correlate the results with their clinical outcome.Patients and Methods: This study was conducted on 50 de novo younger AML patients (median age 44). Quantitative real-time polymerase chain reaction (QRT-PCR) was used to assess the expression level of the PIM-2 gene. The transcription level of the target gene (PIM-2) was normalized to that of the reference gene (GAPDH). Twenty control samples were withdrawn from 20 age- and sex-matched individuals for the analysis of the results using the 2−ΔΔCT method. On day 28 following induction chemotherapy, patients’ bone marrow (BM) was examined for evaluation of their remission status.Results: PIM-2 gene expression was higher among AML patients who did not achieve complete remission (CR); also, it was higher in patients in the intermediate and poor cytogenetic risk groups. A significant positive correlation was found between PIM-2 level and BM blasts on day 28. In AML patients, PIM-2 has been discovered to be an independent predictive factor for achieving CR following standard induction treatment. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were performed for PIM-2 level at diagnosis to evaluate its role in achieving remission after induction. It was found that PIM-2 at cutoff ≤ 1.6 had an AUC (0.903) with a sensitivity (90.48%) and specificity (86.21%), P < 0.001.Conclusion: Overexpression of the PIM-2 gene is associated with induction failure and low CR.Keywords: AML, PIM-2 gene, QRT-PCR, induction chemotherapy, complete remission

Aquaculture industry suffers significant limitations such as low resistance to diseases and expensive feed. This study investigated the antibacterial and immunostimulatory activities of ZnO-Ulva lactuca nanocomposite (ZnO-Ul NC) in the Procambarus clarkii. Zinc oxide nanoparticles (ZnO NPs) and ZnO-Ul NC were synthetized and characterized by electron microscopies as well as Fourier transform infrared spectroscopy. ZnO NPs and ZnO-Ul NC inhibited the growth of the isolated species Citrobacter freundii and Enterobacter hormaechei. For immunostimulatory evaluation, six crayfish groups (control, U. lactuca, ZnO L, ZnO H, ZnO-Ul L, and ZnO-Ul H) were fed on commercial diet, Ulva lactuca powder, and low or high dose of ZnO NPs or ZnO-Ul NCs, respectively for 90 days. The highest levels of total hemocyte count, granular cells%, phenoloxidase (PO) activity in hemolymph, and NO, superoxide dismutase (SOD), and GSH in hepatopancreas were all reported in the ZnO-Ul groups. The expression of proPO, SOD, and lysozyme exhibited the highest upregulation in the ZnO-Ul H group. Taken together, dietary ZnO-Ul NC significantly improved the non-specific immunity and antioxidant milieu of the crayfish at the genomic and proteomic levels. ZnO-Ul NC is cost effective, easily synthesized, and a promising immunostimulant for Procambarus clarkii that could be used in the aquaculture., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Two spargana of 5 and 7 cm long were removed from the right-hand palm of 14-year-old girl at the General Hospital, Qalyubia, Egypt. Sparganum is the 2nd larval stage (pleurocercoid) of Diphyllobothrid cestode species develops in the vertebrate second intermediate host through ingestion of the crustacean first intermediate host.Dogs and cats are the final hosts get infected through predation of the second vertebrate host.Human attracts infection through drinking water contaminated with the infected crustacean host or consumption of the flesh of of vertebrate hosts such as frogs and reptilian species. The surgically removed specimens were parsitologically identified as a non-proliferative metacestodes of a spirometran species that then on molecular analysis proved to be Spirometra erinaceieuropaei . The present report has allocated Egypt on the world sparganosis map.Molecular characterization of 28 S rRNA of S. erinaceieuropae and correlation to other Spirometra spp. from the Nile countries, particularly Ethiopia and Lake Victoria countries where the Nile waters originate, and from China were dealt with. Drinking of contaminated fresh water is the only proposed mode of infection in Egypt., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© Indian Society for Parasitology 2023.)

Introduction: Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients., Methods: This prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed., Results: There was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CD11b among cirrhotic patients., Conclusions: Elective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CD11b on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings., Competing Interests: Conflicts of interest The author declares no conflicts of interest., (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Theileriosis is a tick-borne protozoal disease caused by a piroplasm of the genus Theileria. Hard ticks are obligate hematophagous ectoparasites that serve as vectors of Theileria spp. Studies of the presence of theileriosis in Egyptian dogs and associated ticks are scarce. This study was conducted to detect and identify Theileria spp. in dogs and Rhipicephalus sanguineus ticks and to monitor the epidemiological data of this disease. The prevalence rates of Theileria equi infection were 12.02%, 0.73%, 2.93%, and 1.83% by microscopic examination of dog blood, tick hemolymph, tick midgut, and tick salivary smears, respectively. Conversely, the T. equi prevalence in dog blood and associated ticks assessed by PCR was 25.81% and 10.42%, respectively. Epidemiological data about Theileria infection revealed a significant difference in the infection between different seasons and different dog breeds (p value <0.05), whereas host, sex, and age of dogs had no significant effect on the infection. Sequencing of PCR products showed that all PCR positive samples were infected with T. equi. Transmission electron microscopy (TEM) described the different stages of Theileria in the midgut and salivary gland of infected ticks. The current study confirmed that T. equi is not specific to equine hosts, and confirmed that dogs are a susceptible host to T. equi., (© 2022 Royal Entomological Society.)

Dendritic cell (DC) vaccines are promising for immunotherapy, and their production using CD34 + hematopoietic stem cells (HPSCs) from patients with chronic myelogenous leukemia (CML) and healthy donors is well established. However, the generation of CD1a + CD14 - DCs and their functional properties in patients with CML remain elusive. Here, we aimed to study the biology of DCs generated from CD34 -/low HPSCs and evaluate the status of their BCR/ABL translocation, ability to stimulate T cells, and capacity of endocytosis compared to DCs derived from CD34 + HPSCs from both patients with CML and healthy donors. CD1a + CD14 - DCs were generated from CD34 -/low HPSCs and evaluated morphologically and functionally. CD34 + cells are frequently selected for transplantation and the entire CD34 -/low HPSC fraction is wasted. Here, we anticipated the CD34 - HPSC subset to constitute an invaluable source for acquiring DCs for immunotherapy. CD34 + and CD34 - HPSCs were sorted from the bone marrow samples of CML patients and healthy donors and differentiated ex vivo in a similar way. DCs from CD34 - Lin - and CD34 + Lin - HPSCs expressed comparable surface markers (CD80, CD83, CD86, HLA-DR, CD40, and CD54). Functional analysis revealed that DCs acquired from both subsets retained a potent allogeneic T cell stimulatory capacity and an efficient phagocytic ability and showed a similar BCR/ABL translocation status. In conclusion, DCs were successfully differentiated from the CD34 - Lin - cell subset and showed potent functional capacities, indicating their potential for application in immunotherapy and basic research., Competing Interests: None., (AJTR Copyright © 2023.)

Introduction: Hepatic encephalopathy (HE) is a complication of liver failure, with neurological manifestations ranging from minimal HE (MHE) to deep coma (overt HE)., Aim of the Study: To demonstrate the role of functional magnetic resonance imaging (magnetic resonance spectroscopy [MRS] and apparent diffusion coefficient [ADC] value) in the assessment and grading of HE in cirrhotic patients., Material and Methods: A prospective cohort study was conducted on three groups: group I - 20 healthy controls, group II - 25 cirrhotic patients with MHE, and group III - 25 cirrhotic patients with overt HE. Each group was subjected to MRS, diffusion-weighted imaging, and neuropsychological examinations. At 1 H-MRS, the glutamate/glutamine complex (Glx), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and creatine (Cr) were determined in the basal ganglia or thalamus. The metabolic ratios and ADC values of Glx/Cr, MI/Cr, Cho/Cr, and NAA/Cr were determined., Results: The brain metabolite Glx increased with a significant correlation to HE grade ( p = 0.001). Other brain metabolites, such as Cho and mI, decreased significantly ( p = 0.001). Two brain metabolites (NAA and Cr) remained unchanged across all HE grades and the control group ( p = 0.47 and 0.38, respectively). There was an increase in the Glx/Cr ratio and a decrease in the mI/Cr and Cho/Cr ratios. In addition, ADC values were significantly higher in cirrhotic patients with HE than in the control group., Conclusions: ADC values and 1 H-MRS are imaging modalities that have the potential to detect MHE and grade HE in cirrhotic patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Clinical and Experimental Hepatology.)

Introduction: Hemogram parameters have been recently proposed as markers of inflammation in various studies from different parts of the world. Two of these hemogram parameters are red cell distribution width (RDW) and mean platelet volume (MPV)., Aim: To evaluate the relation between RDW and MPV with disease activity of rheumatoid arthritis. To assess whether RDW and MPV can be used to follow disease activity in RA patients., Methods: This is an observational cross-sectional study that was carried out on 60 rheumatoid arthritis patients who fulfilled the ACR/EULAR2010 classification criteria of RA attending to Rheumatology and Rehabilitation inpatient and outpatient clinics at Zagazig University Hospitals. All cases were subjected to full history taking, clinical examination, and laboratory investigations; differential complete blood picture (CBC), acute phase reactants (CRP and ESR), rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (anti-CCP) antibodies. Disease activity was measured by disease activity score 28 (DAS28)., Results: The cut-off levels of RDW and MPV were 14.85 and 11.25. Patients with RDW>14.85 had higher Disease Activity Score 28 (DAS28; p=0.0003), ESR (p=0.0001) and CRP (p=0.0001). RDW was positively correlated with disease activity markers (ESR, CRP and DAS28) in rheumatoid arthritis patients. But, DAS28 was not different between patients with MPV>11.25 and <11.25., Conclusion: RDW was strongly correlated with disease activity. Also, RDW was better than ESR and CRP in detecting RA disease activity. According to these findings we suggest that RDW can be used in clinics to follow disease activity. In addition, RDW is widely available; as it's usually included in routine complete blood picture and there will be no need for further cost., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background: The incidence or recurrence of tick-borne diseases (TBDs) in animals and humans is increasing rapidly worldwide, but there is insufficient information about TBDs infecting dogs in Egypt. Thus, the present study was conducted to screen and genetically identify tick-borne pathogens (TBPs) in dogs and associated ticks by microscopic examination and polymerase chain reaction (PCR)., Methods: In Cairo and Giza governorates, 208 blood samples were collected from dogs of different breeds, ages, and sex. In addition, 1266 dog-associated ticks were collected (546 ticks were used to prepare hemolymph smears, and 720 ticks were kept in 70% ethanol until PCR analysis). PCR was applied to 124 dog blood samples and 144 tick pools prepared from 720 ticks., Results: All ticks collected from dogs were Rhipicephalus sanguineus (s.l.). Microscopic examination revealed that TBP prevalence among dogs was 23.56% (49/208), including Anaplasma and Ehrlichia with 11.1% (23/208) and Babesia canis with 8.2% (17/208). Hepatozoon canis was not detected in blood smears. Co-infections with two pathogens were visible in 4.33% (9/208) of examined dogs. The prevalence of TBPs in hemolymph smears was 45.97% (251/546) including 35.89% (196/546) for H. canis, 8.1% (44/546) for B. canis, and 2.01% (11/546) for Anaplasmataceae (A. phagocytophilum, A. marginale, A. platys, and E. canis). The overall molecular prevalence rate of TBPs was 25.81% and 29.17% in the blood of examined dogs and in ticks, respectively. The molecular prevalence of Anaplasmataceae family, Babesia canis, and H. canis in dog blood samples was 19.35%, 6.45%, and 0.0%, respectively, while in ticks, it was 20.83%, 5.55%, and 2.8%, respectively. A sequential analysis identified six different species of TBPs, namely B. canis vogeli, Hepatozoon canis, A. phagocytophilum, A. marginale, A. platys, and E. canis. The obtained sequences were submitted to GenBank and assigned accession numbers., Conclusions: The present study detected a wide range of TBPs (B. canis, H. canis, A. platys, A. phagocytophilum, A. marginale, and E. canis) that are considered a threat to domestic animals and humans in Egypt. Hepatozoon canis and A. marginale were reported in dogs and associated ticks for the first time in Egypt., (© 2022. The Author(s).)

Background: Acanthamoeba spp. are one of the free-living amoeba that spread worldwide causing keratitis. Owing to the increase in the use of lenses, whether for medical or cosmetic purposes, the incidence of disease increases every year. Contamination of the lenses with the Acanthamoeba trophozoites or cysts may lead to eye infection and cause sight-threatening keratitis in human. We isolated Acanthamoeba spp. from new lenses, used lenses, and contact lens disinfecting solutions and identified them based on morphological characteristics and molecular test., Methods: New and used lenses and contact lens disinfecting solutions were cultured on monogenic media. Light and scanning electron microscope was used to identify Acanthamoeba spp. morphological features. Genotype identification was also evaluated using PCR sequencing of 18S rRNA gene specific primer pair JDP1 and JDP2., Results: A hundred samples were examined, 29 (29%) were infected with Acanthamoeba spp. That belonged to two strains of Acanthamoeba (Acanthamoeba 41 and Acanthamoeba 68). 18S rRNA of the Acanthamoeba 41 had 99.69% sequence identity to Acanthamoeba castellanii clone HDU-JUMS-2, whereas Acanthamoeba 68 had 99.74% similar pattern to that of Acanthamoeba sp. isolate T4 clone ac2t4 that are morphologically identified as Acanthamoeba polyphaga. The obtained data revealed that the isolated strains belong to T4 genotype that was evolutionarily similar to strains isolated in Iran., Conclusions: Cosmetic lenses and disinfectant solutions are a major transmissible mode for infection. This genotype is common as the cause of Acanthamoeba keratitis. To avoid infection, care must be taken to clean the lenses and their preservative solutions and prevent contamination with the parasite., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Hemogram parameters have been recently proposed as markers of inflammation in various studies from different parts of the world. Two of these hemogram parameters are red cell distribution width (RDW) and mean platelet volume (MPV)., Aim: To evaluate the relation between RDW and MPV with disease activity of rheumatoid arthritis. To assess whether RDW and MPV can be used to follow disease activity in RA patients., Methods: This is an observational cross-sectional study that was carried out on 60 rheumatoid arthritis patients who fulfilled the ACR/EULAR2010 classification criteria of RA attending to Rheumatology and Rehabilitation inpatient and outpatient clinics at Zagazig University Hospitals. All cases were subjected to full history taking, clinical examination, and laboratory investigations; differential complete blood picture (CBC), acute phase reactants (CRP and ESR), rheumatoid factor (RF) and anti-cyclic-citrullinated peptide (anti-CCP) antibodies. Disease activity was measured by disease activity score 28 (DAS28)., Results: The cut-off levels of RDW and MPV were 14.85 and 11.25. Patients with RDW>14.85 had higher Disease Activity Score 28 (DAS28; p=0.0003), ESR (p=0.0001) and CRP (p=0.0001). RDW was positively correlated with disease activity markers (ESR, CRP and DAS28) in rheumatoid arthritis patients. But, DAS28 was not different between patients with MPV>11.25 and <11.25., Conclusion: RDW was strongly correlated with disease activity. Also, RDW was better than ESR and CRP in detecting RA disease activity. According to these findings we suggest that RDW can be used in clinics to follow disease activity. In addition, RDW is widely available; as it's usually included in routine complete blood picture and there will be no need for further cost., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and is considered the second cause of cancer-related death., Aim: The aim of the study is to assess the usefulness of real-time shear-wave elastography in differentiating HCC from other hepatic focal lesions., Patients and Methods: The current study was conducted on 110 patients in addition to 10 healthy subjects, divided into four groups as follows: liver cirrhosis, HCC, hepatic focal lesions other than HCC, and control. Demographic, laboratory and imaging data were collected and then elastographic assessment of the hepatic focal lesions and the surrounding liver parenchyma using elastograph point quantification (ElastPQ) (iU22x MATRIX, Philips) was done., Results: ElastPQ (iU22x MATRIX, Philips) has shown its ability to differentiate between HCC and cystic focal lesions, HCC and cholangiocarcinoma, and HCC and focal nodular hyperplasia (FNH). Cystic lesions demonstrated lower stiffness in comparison to HCC; however, cholangiocarcinoma and FNH demonstrated higher stiffness in comparison to HCC. ElastPQ was unable to differentiate between stiffness in both 'HCC and hemangioma' and 'HCC and metastatic focal lesions'. ElastPQ showed that HCC, cystic focal lesions, and cholangiocarcinoma had lower stiffness in comparison to their surrounding liver parenchyma, whereas FNH had higher stiffness in comparison to the surrounding liver parenchyma. ElastPQ showed that the surrounding liver parenchyma of the HCC group has the highest stiffness amongst all studied hepatic focal lesions surrounding liver parenchyma., Conclusion: 'Point' shear-waves elastography (ElastPQ; Philips iU22x MATRIX, Philips) is a noninvasive, quantitative and nonradiating method for evaluation of tissue elasticity, and is helpful in differentiating HCC from other hepatic focal lesions., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D 3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D 3 , VI-cancer + cisplatin nanoparticles + vitamin-D 3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D 3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D 3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results., (© 2020 International Union of Biochemistry and Molecular Biology.)

Suspect has been directed towards some direct acting antivirals (DAAs) due to their reported association with hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients. The mechanisms behind HCC development, following CHC treatment, were not well understood and may be linked to genetic variabilities in different patients which affect several cytokine productions involved in angiogenesis and inflammation. Of these variabilities, is the genetic polymorphisms in the interleukin-17 (IL-17) A receptor gene. Being an important pleiotropic cytokine, this study aimed to investigate the association between haplotypes in IL-17A receptor rs2275913 and rs3819024 and development of HCC in CHC patients treated with either triple therapy (sofosbuvir (SOF), pegylated interferon-alpha-2a (Peg-IFNα-2a) & ribavirin(RBV)) or with dual therapy (Peg-IFNα-2a&RBV). A cohort of 100 CHC patients was recruited in this study. Samples were tested for single nucleotide polymorphism (SNPs) in IL-17A receptor (rs2275913 and rs3819024) using TaqMan Genotyping assay. Our results showed that the presence of G-G haplotype in IL-17A (rs2275913& rs3819024) is inversely associated with HCC development in patients receiving triple therapy. While, high serum AFP levels are directly associated with HCC development in patients receiving triple therapy. However, in patients receiving dual therapy, HCC development was only associated with high serum alpha fetoprotein (AFP) levels and was not correlated to any specific allele in our studied SNPs. Such results highlight the importance of IL17A receptor gene haplotyping in the prediction of HCC development in patients receiving triple therapy. These results will aid in performing tailored, personalized strategy for CHC treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1β, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury., Competing Interests: The authors declare no conflict of interest.

Objective: To asses clinically and radiographically the effect of using two types of coronal plug materials in revascularization of non-vital immature teeth., Methods: A total of 26 necrotic immature permanent anterior teeth were enrolled for pulp revascularization using a double antibiotic mix for root canal disinfection. They were randomly divided into the following based on coronal plug materials used: Biodentine (Group I) and white Mineral Trioxide Aggregate (Group II; n = 13). Clinical and radiographic assessments were performed after 3, 6, 9, and 12 months., Results: When comparing the overall clinical successes and percentage of increase in root length between the two groups, there was no statistically significant difference (P > 0.05). There was a significant difference in the distribution of discoloration between the two groups. One case was reported in Group I, and seven cases were reported in Group II (P = 0.01)., Conclusions: Both Biodentine and Mineral Trioxide Aggregate were successful clinically regarding the resolution of signs and symptoms associated with the necrotic teeth., (© 2019 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the present study, we investigated the impact of camel whey protein (CWP) on the survival of primary acute myeloid leukemia (AML) cells that were isolated from 20 patients diagnosed with AML. We found that CWP induced apoptosis in the primary AML cells without affecting the normal PBMCs that were isolated from healthy individuals, as determined by PI/annexin V double staining followed by flow-cytometry analysis. Furthermore, we demonstrated that these primary AML cells exhibited aberrant phosphorylation of AKT, mTOR and STAT3. Treatment of AML cells with CWP mediated significant reduction in the phosphorylation of AKT, mTOR and STAT3. Additionally, we demonstrated that blockade of PI3K/AKT signaling pathway by wortmannin (WM) impaired the expression of Bcl-2 and Bcl XL in the primary AML cells, suggesting an essential cross-talk between PI3K and Bcl-2 that maintains the survival of AML cells. In this context, treatment of AML cells with CWP disrupted the PI3K/Bcl-2 cross-talk; significantly downregulated the expression of anti-apoptotic Bcl-2 family members Bcl-2 and Bcl XL ; markedly upregulated the expression of the pro-apoptotic Bcl-2 family members Bak and Bax; and subsequently sensitized tumor cells to growth arrest. Our data revealed the therapeutic potential of CWP and the underlying mechanisms against leukemia.

Aim: The aim is to analyze the sleep architecture using polysomnography (PSG) in patients with Juvenile Myoclonic Epilepsy (JME): (newly diagnosed and those on valproate drug) attending epilepsy clinic at Alexandria University Hospitals., Methods: This study involved 20 patients with JME on valproate (age: 22.40 ± 5.80 years; M:F = 6:14), 20 newly diagnosed patients (age: 18.55 ± 6.0 years; M:F = 6:14), and 20 matched healthy controls (age: 22.10 ± 5.0 years; M:F = 6:14). Clinical assessment, electroencephalogram (EEG), evaluation with comprehensive sleep questionnaire, and PSG were done for all patients., Results: PSG showed significant alterations in sleep architecture in the total JME group in the form of reduced mean sleep efficiency (p = 0.001 ∗ ), increased mean Rapid eye movement (REM) onset latency (p = 0.046 ∗ ), decrease mean REM percentage (p = 0.011 ∗ ), increased mean wakefulness after sleep onset (p = 0.018 ∗ ), increase the index of total arousal (p = 0.005 ∗ ), increased mean periodic limb movement index (P = 0.001 ∗ ), and reduced apnea hypopnea index (P = <0.001) in comparison to control group. Valproate treated group showed increased sleep efficiency (p = 0.040 ∗ ), decreased REM arousal index (P = 0.012), longer stage 3 (P = 0.038), and prolonged stage 2 (P = 0.049 ∗ ) than the newly diagnosed group., Conclusions: Sleep architecture was significantly disturbed in JME, with improvement in sleep efficiency in valproate treated patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The development of a portable oxygen concentrator is of prime significance for patients with respiratory problems. This paper presents a portable concentrator prototype design using the pressure/vacuum swing adsorption (PVSA) cycle with a deep evacuation step (-0.82 barg) instead of desorption with purge flow to simplify the oxygen production process. The output of the oxygen concentrator is a ~90 vol % enriched oxygen stream in a continuous adsorption and desorption cycle (cycle time ~90 s). The size of the adsorption column is 3 cm in diameter and 20 cm in length. A Li⁺ exchanged 13X nanosize zeolite is used as the adsorbent to selectively adsorb nitrogen from air. A dynamic model of the pressure and vacuum swing adsorption units was developed to study the pressurization and depressurization process inside the microporous area of nanosized zeolites. The describing equations were solved using COMSOL Multiphysics Chemical Engineering module. The output flow rate and oxygen concentration results from the simulation model were compared with the experimental data. Velocity and concentration profiles were obtained to study the adsorption process and optimize the operational parameters., Competing Interests: The authors declare no conflict of interest.

The balance between free radicals and antioxidants is an important factor for maintaining health and slowing disease progression. The use of antioxidants, particularly natural antioxidants, has become an important strategy for dealing with this cause of widespread diseases. Natural antioxidants have been used as therapeutic tools against many diseases because they are safe, effective, and inexpensive and are among the most commonly used adjuvants in the treatment of several diseases. Camel whey protein (CWP) is considered a strong natural antioxidant because it decreases oxidative stress, enhances immune system function, and increases glutathione levels. The structure of CWP is very similar to that of other types of whey protein from different types of milk. CWP contains many components, such as lactoferrin (LF), lactalbumin, lactoglobulins, lactoperoxidase, and lysozyme, and is rich in immunoglobulins. However, in contrast to other WPs, CWP lacks β-lactoglobulin, the main cause of milk allergies in children. The components of CWP have many beneficial effects, including stimulation of both innate and adaptive immunity and anti-inflammatory, anticancer, antibacterial, and antiviral activities. Recently, it has been shown that CWP and its unique components can facilitate the treatment of impaired diabetic wound healing. However, the molecular mechanisms underlying the protective effects of CWP in human and other animal disorders are not fully understood. Therefore, the current review presents a concise summary of the scientific evidence of the beneficial effects of CWP to support its therapeutic use in disease treatment and nutritional intervention.

Type I diabetes (T1D) is a characterized by the inflammation of pancreatic islets and destruction of β cells. Long and persistent uncontrolled diabetes tends to degenerate the immune system and increase the incidence of infections in diabetic individuals. Most serious diabetic complications are mediated by the free radicals, which damage multiple cellular components through direct effects of the cell cycle regulatory proteins. Camel whey protein (CWP) has antioxidant activity and decreases the effects of free radicals. However, the effects of CWP on lymphoid organs have not been studied in the context of diabetes. Therefore, the present study was designed to investigate the dietary influence of CWP supplementation on the lymphoid organs in streptozotocin (STZ)-induced type 1 diabetic mouse model. Three experimental groups were used: non diabetic control mice, diabetic mice, and diabetic mice treated with CWP. Induction of diabetes was associated with a marked reduction in glutathione (GSH) levels; decreased activities of GSH peroxidase (GSH Px), manganese superoxide dismutase (MnSOD) and catalase; increased reactive oxygen species (ROS) levels and iNOS activity in plasma and lymphoid organs. Furthermore, diabetic mice exhibited alterations in the expression of Bax and Bcl-XL, and subsequently pathological alterations in the architecture of the bone marrow, pancreas, thymus, and spleen. Interestingly, treatment of diabetic mice with CWP robustly restored glucose, insulin, GSH, and ROS levels and the activities of GSH Px, MnSOD, catalase and iNOS. Additionally, supplementation of diabetic mice with CWP improvement in the architecture of lymphoid tissues and rescued from apoptosis through direct effects on the Bax and Bcl-XL proteins. These data revealed the therapeutic potential of CWP against diabetic complications mediated damages of lymphoid organs., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: Pseudomonas aeruginosa is one of the most virulent nosocomial pathogens worldwide. Quorum sensing (QS) regulates the production of pathogenic virulence factors and biofilm formation in P. aeruginosa. The four genes lasR, lasI, rhlR,and rhlI were found to regulate this QS system. In this study, we aimed to assess the correlation between these four genes and QS-dependent virulence factors and to detect the inhibitory effect of clove oil on QS., Methodology: Fifty P. aeruginosa clinical isolates were collected. Susceptibility to different antibiotics was tested. Virulence factors including biofilm formation, pyocyanin production, and twitching motility were phenotypically detected. QS genes were amplified by polymerase chain reaction (PCR), and one strain subsequently underwent sequencing. The inhibitory effect of clove oil on virulence factors was also tested., Results: A positive correlation was found between biofilm formation and the presence of lasR and rhlI genes. Twitching motility was positively correlated with the presence of lasR, lasI, and rhlI genes. On the other hand, no correlation was found between pyocyanin production and any of the studied genes. Only one isolate amplified all the tested QS gene primers, but it did not express any of the tested virulence factors phenotypically. Sequence analyses of this isolate showed that the four genes had point mutations., Conclusions: Results emphasize the importance of QS in P. aeruginosa virulence; however, QS-deficient clinical isolates occur and are still capable of causing clinical infections in humans. Also, clove oil has an obvious inhibitory effect on QS, which should be clinically exploited.

Background: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease with a complex pathophysiology. The clinical features of NAFLD include obesity, insulin resistance (IR) and dyslipidemia. Consumption of a diet high in saturated fats and sucrose is an important factor in the increasing occurrence of these metabolic disorders, primarily NAFLD and IR. We sought to assess the role of a high-fat, high-sucrose (HFS) diet in the promotion of NAFLD and to evaluate the effects of quercetin (Q), berberine (BB) and o-coumaric acid (CA) on modulation of these disorders., Methods: Fifty male rats were divided into 2 main groups as follows: group 1 comprised 10 rats fed a standard diet (SD), and group 2 comprised 40 rats fed an HFS diet for 6 weeks and then subdivided equally into 4 groups; one of these groups served as the HFS diet and each of the other three groups received daily supplementation with either Q, CA or BB for 6 weeks., Results: In the present study, several metabolic disorders were induced in our laboratory animal model, as evidenced by histological and biochemical changes. These alterations included serum and hepatic dyslipidemia (i.e., increased triglyceride, total cholesterol and low-density lipoprotein levels and decreased high-density lipoprotein levels), alterations in metabolic enzyme activities (lipase, glycerol-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase), histological changes in the liver (micro- and macrovesicular steatosis) and the downregulation of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue and the liver. Daily oral supplementation with Q, CA or BB for 6 weeks after NAFLD induction had a hypolipidemic action and modulated metabolic markers., Conclusion: We showed that an HFS diet is able to promote NAFLD, and our results suggest that CA and BB are promising complementary supplements that can ameliorate the metabolic disorders associated with an HFS diet; however, Q requires further investigation.

Background: Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity)., Objectives: To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex., Materials and Methods: An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups., Results: High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex., Conclusions: Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Oxidative stress has been proven to be involved in cisplatin (CP)-induced toxicity. The present study was designed to evaluate the antioxidant activity of Vit C, N,N'-diphenyl-p-phenylenediamine (DPPD) and L-cysteine against CP-induced testicular oxidative damage in rats. Our data indicated significant increases in lipid peroxides (LPO), total peroxides and superoxide anion levels in testes of rats treated with CP (2 mg/kg/week, for 4 weeks) that was associated with a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). The contents of glutathione (GSH), Vit E and Vit C were significantly lower in CP treated testes compared with these of control. The co-administration of CP with DPPD or L-cysteine significantly reduced the elevation in LPO, however the co-administration of CP with Vit C, DPPD or L-cysteine reduced the effect of CP on superoxide anion and antioxidant enzymes and also on the antioxidants contents. The administration of Vit C, DPPD or L-cysteine before CP injection improved the histological pictures and reduced the number of apoptotic cells and DPPD was more efficient. In conclusion, DPPD is a potent antioxidant, against CP-induced testicular oxidative damage, as compared with Vit C and L-cysteine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background and Purpose: Retinal vascular caliber changes have been shown to predict stroke, but the underlying mechanism of this association is unknown. We examined the relationship between retinal vascular caliber with brachial flow-mediated dilation (FMD), a measure of systemic endothelial function., Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of persons 45 to 84 years of age residing in 6 US communities free of clinical cardiovascular disease at baseline. Brachial FMD data were collected at baseline (July 2000 to June 2002), and retinal vascular caliber was measured from digital retinal photographs at the second examination, immediately after the first (August 2002 to January 2004). Data were available for 2851 participants for analysis., Results: The mean brachial FMD was 4.39+/-2.79%. After adjusting for age and gender, brachial FMD was reduced in persons with wider retinal venular caliber (changes in FMD -0.25, 95% CI, -0.36, - 0.13; P<0.001, per SD increase in venular caliber). This relationship persists after adjusting for systolic blood pressure, serum total cholesterol, use of lipid-lowering and antihypertensive medication, body mass index, current smoking status, and hemoglobinA(1C) (-0.18; 95% CI -0.30, - 0.06; P=0.004, per SD increase in venular caliber). Brachial FMD was not associated with retinal arteriolar caliber., Conclusions: Persons with wider retinal venules have reduced brachial FMD, independent of other vascular risk factors. This suggests that retinal venular caliber, previously shown to predict stroke, may be a marker of underlying systemic endothelial dysfunction.

Background: Ostial lesions are a difficult subset associated with suboptimal outcomes after percutaneous coronary intervention (PCI). The aim of this study was to analyze outcomes of ostial lesions in contemporary Australian interventional practice., Methods: The study population comprised 1,713 consecutive patients who underwent PCI for proximal lesions of the left anterior descending, left circumflex, and right coronary arteries, who were prospectively enrolled in the Melbourne Interventional Group Registry (February 2004-December 2006). We compared the in-hospital, 30-day, and 1-year outcomes of the 109 patients undergoing PCI for ostial, with the 1,604 patients with proximal nonostial lesions. Left main and bifurcation lesions were excluded., Results: Patients in the ostial group were older (mean age 68.8 +/- 11 vs. 64.9 +/- 12 years; P = 0.001), and there was a greater proportion of women (38.5% vs. 28.0%; P = 0.021). Other clinical characteristics were similar. The nonostial group were more likely receive a stent (94.6% vs. 87.2%; P = 0.005) but drug-eluting stents (DES) were deployed more often in the ostial group (47.9% vs. 66.1%; P < 0.0001). There was lower procedural success, with no significant difference in in-hospital death, bleeding or emergency PCI, but unplanned in-hospital coronary artery bypass grafting was more frequent in the ostial group (4.8% vs. 1.0%; P = 0.007). There was no difference in 30-day major adverse cardiac events. However, 12-month death (8.8% vs. 4%, log rank P = 0.032) and MACE (24.2% vs. 13.8%, log rank P = 0.005) were higher in the ostial group than the nonostial group with trends to increased incidence of myocardial infarction (6.6% vs. 4.7%, P = NS), and target vessel revascularization (13.2% vs. 7.9%, P = NS)., Conclusion: In contemporary, Australian interventional practice, PCI for ostial lesions is associated with a high incidence of adverse outcome at one year despite the introduction of DES.

Objectives: Recent population-based studies have shown that retinal vascular caliber may predict the risk of clinical coronary artery disease (CAD) events. Whether this association is related to macro- or microvascular mechanisms remains unknown. We investigated the relationship of retinal vascular caliber with severity and extent of CAD in symptomatic cardiac patients., Materials and Methods: Overall, 98 patients attending diagnostic coronary angiography were recruited. Coronary angiography was used to assess for the severity and extent of CAD. Digital retinal photography was performed immediately prior to cardiac catheterization, and retinal vascular caliber was measured from these photographs by using a computer program and summarized as central retinal arteriolar (CRAE) and venular (CRVE) equivalents., Results: Retinal arteriolar and venular calibers were not associated with increasing severity of CAD, as assessed by Leaman scores (CRAE/CRVE: P for trend=0.17/0.57), presence of clinically significant CAD (CRAE/CRVE: P=0.35/0.32), or number of diseased vessels (CRAE/CRVE: P for trend=0.18/0.69)., Conclusions: Retinal vascular caliber changes are not associated with the severity of obstructive CAD in symptomatic patients. These data suggest that the association of retinal vascular caliber with clinical CAD seen in epidemiological studies may not be applicable to clinical symptomatic patients and may be related to microvascular, rather than macrovascular, mechanisms.

Tako-tsubo-like cardiomyopathy is characterized by acute chest pain, electrocardiographic changes and increased cardiac enzymes in the absence of obstructive coronary vessel disease. We describe the development of tako-tsubo-like cardiomyopathy in an elderly woman after the use of an EpiPen for generalized urticaria and angioedema. As adrenaline may participate in the pathogenesis of this condition, the need for careful patient selection and education in the use of adrenaline self-injectors remains imperative.

Background and Purpose: There are concerns that cardiac catheterization may cause retinal embolization, a risk marker for cerebrovascular emboli and stroke. We describe the incidence of acute retinal embolism after cardiac catheterization., Methods: One hundred unselected patients attending a tertiary referral center for diagnostic cardiac catheterization were recruited. Digital retinal photography (optic disc and macular fields) was performed precatheterization and within 3 hours postcatheterization. New retinal emboli were identified by a senior researcher and confirmed by a retinal specialist., Results: There was one case of retinal embolus precatheterization. Two patients (incidence 2.02%; 95% CI, 0.25 to 7.11) developed new retinal arteriolar emboli after catheterization. No patient developed clinically apparent visual or neurological changes., Conclusions: The risk of acute retinal embolism immediately after cardiac catheterization is 2%. This finding indicates that the retinal, and possibly the cerebral circulation, may be compromised more frequently than is clinically apparent as a complication of cardiac catheterization.

Purpose: To assess reliability and reproducibility of different analysis methods for retinal capillary flow, volume, and velocity from scanning laser Doppler flowmetry (SLDF) topography., Material and Methods: SLDF topography analysis using the default retinal flowmeter (HRF) were compared to that using automatic full-field perfusion image analyzer (AFFPIA) and quantified as intraclass correlation coefficients (ICC)., Results: The AFFPIA full-field method had the highest reliability, with ICC 0.99 for capillary flow. The reproducibility using the AFFPIA full-field method was high ICC 0.74 for capillary flow., Conclusions: The AFFPIA full-field method is highly reliable and superior to the default HRF software.

Background: The success rate of percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) is relatively low. Further evaluation of CTO lesion with CT coronary angiography (CT-CA) may help to better select patients that would benefit from percutaneous revascularization. We aimed to test the possible association between failed PCI and transluminal calcification of CTO as assessed by CT-CA., Methods: Patients with CTO awaiting PCI were scanned with a 16-slice CT. A cardiologist and a radiologist assessed transluminal calcification of CTO lesions on CT images while an interventional cardiologist at a core laboratory assessed conventional variables of invasive fluoroscopic coronary angiography (FCA) associated with failed PCI of CTO. The significance of CT and FCA variables in association with failed PCI were analyzed., Results: In a cohort of 39 patients with 43 CTO lesions, 24 lesions were successfully revascularized. Transluminal calcification > or =50% as assessed on CT-CA was strongly associated with failed PCI (odds ratio [OR] of PCI success = 0.10, 95% confidence interval [CI]: 0.02-0.47, P = 0.003). Blunt stump as seen on FCA was also associated with failed PCI (OR of PCI success = 0.24, 95% CI: 0.07-0.86, P = 0.029). There was no significant evidence to support that the duration of CTO, presence of side branch and bridging collaterals, and the absence of microchannels as assessed with FCA were associated with failed PCI. On multivariate analysis, transluminal calcification > or =50% on CT-CA was the only significant predictor of failed PCI., Conclusions: Heavy transluminal calcification as assessed with CT-CA is an independent predictor of failed PCI of CTO. CT-CA may have a role in the work-up of CTO patients prior to PCI.

Background: The use of antilymphocyte agents has improved patient and graft survival in hematopoietic stem cell and solid organ transplantation but has been associated with the development of short-term toxicities as well as long-term complications., Case Presentation: We report a young female with Fanconi anemia who received antithymocyte globulin as part of the conditioning regimen prior to her planned allogeneic hematopoietic stem cell transplant at King Faisal Specialist Hospital and Research Centre in Riyadh. She developed sudden and severe hepatotoxicity after receiving the first dose of horse antithymocyte globulin, manifested by marked elevation of serum transaminases and mild elevation of serum bilirubin level. Immediately after withdrawal of the offending agent and shifting to the rabbit form of antithymocyte globulin, the gross liver dysfunction started to subside and the hepatic profile results returned to the pre-transplant levels few weeks later. The patient had her allogeneic hematopoietic stem cell transplant as planned without any further hepatic complications. After having a successful allograft, she was discharged from the stem cell transplant unit. During her follow up at the outpatient clinic, the patient remained very well and no major complication was encountered., Conclusion: Hepatotoxicity related to the utilization of antithymocyte globulin varies considerably in severity and may be transient or long standing. There may be individual or population based susceptibilities to the development of side effects and these adverse reactions may also vary with the choice of the agent used. Encountering adverse effects with one type of antithymocyte agents should not discourage clinicians from shifting to another type in situations where continuation of the drug is vital.

The ATP-sensitive potassium (K(ATP)) channel is a distinct type of potassium ion channel that is found in the vascular smooth muscle cells of a variety of mammalian species, including humans. The activity of K(ATP) channels is determined by many factors including cellular ATP and ADP levels, thus providing a link between cellular metabolism and vascular tone through its effects on membrane potential. Experimental studies using inhibitors of K(ATP) channels, such as the sulfonuylurea class of drugs, indicate that these channels modulate coronary vascular tone including the hyperaemia induced by increased myocardial metabolism. This review examines the evidence linking K(ATP) channels to the regulation of coronary vascular tone and the potential clinical implications of pharmacologic therapies that act on K(ATP) channels.

Objective: Previously, deletion 6p23 was generally reported in therapy-related secondary acute myeloid leukemia (AML) as part of complex karyotypes. In this report, we present two young adult patients with de novo AML-M2 and a terminal deletion 6p23 as a sole primary abnormality, confirmed by chromosome 6 specific subtelomeric probes., Methods: Two female patients 35 and 20 yr of age presented with anemia, but no bleeding, infections, lymphadenopathy or organomegaly. Morphological, immunophenotyping, chromosome and fluorescent in situ hybridization (FISH) analysis was performed on bone marrow aspirate cells., Results: A diagnosis of AML-M2 was confirmed in both patients by morphological and immunophenotyping studies. Chromosome analysis in case no. 1 showed deletion 6p23 in 20% of metaphases whereas in case no. 2 the deletion 6p23 was present in 100% metaphases. FISH analysis confirmed the deletion as terminal in both cases. The DEK oncogene at 6p23 in both cases was found not to be deleted., Conclusion: To our knowledge, deletion 6p23 as a sole primary abnormality was reported in only one case. The common morphological, immunophenotypic, and cytogenetic features in our two patients strongly support a separate new entity of de novo AML with deletion 6p23.

Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61+/-8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3-30 microg/min) and SNP (sodium nitroprusside; 0.3-3 microg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanol-rich cocoa does not modify vascular function in patients with established CAD.

Positive coronary artery remodeling is associated with unstable coronary syndromes. Serum inflammatory markers, including high-sensitivity CRP (hsCRP), can predict future risk of acute coronary events in patients with stable coronary artery disease. We sought to elucidate the relationship of specific serum inflammatory markers with intravascular ultrasound (IVUS) estimation of coronary artery remodeling in patients with stable coronary artery disease. Thirty-one sequential patients at our institution undergoing IVUS-assisted percutaneous coronary intervention (PCI) with stable coronary artery disease were enrolled. Automated IVUS pullback and offline analysis were performed in all patients. Images were analyzed for vessel wall area (VWA) and lumen area (LA), at the culprit lesion and at a proximal reference site, and the remodeling index (RI) was calculated. Positive and negative remodeling were defined as a RI of > 1.05 and < 0.95, respectively. ELISA essays were performed for soluble VCAM-1, ICAM-1 and E-selectin. The distribution of data followed a lognormal distribution. By defining arterial remodeling as simply positive or negative, significant differences were identified for log E-selectin only (1.80 +/- 0.04 versus 1.62 +/- 0.05, respectively; p = 0.02). The RI correlation coefficient was 0.38 (p = 0.04) for log sVCAM-1 and 0.42 (p = 0.02) for log sICAM-1. The log E-selection and RI correlation coefficient, although weaker at 0.32, showed a trend toward significance (p = 0.08). There was no significant correlation between log hsCRP and RI (p = 0.42). Using step-wise multivariate analysis, log sVCAM-1 only remained an independent predictor of the RI (p = 0.03). Positive coronary artery remodeling correlates with serological markers of inflammation in patients with stable coronary artery disease.

Purpose: Transient left ventricular dysfunction in patients under emotional or physical stress, also known as tako-tsubo-like left ventricular dysfunction, has been recently been recognized as a distinct clinical entity. The aims of this review are to define this phenomenon and to explore its similarities to the left ventricular dysfunction seen in patients with acute brain injury., Methods: MEDLINE database, bibliographies of each citation for relevant articles, and consultation with clinical experts were used to examine the clinical picture of tako-tsubo-like left ventricular dysfunction., Results: We identified case series and a systematic review that report on patients with this syndrome. This phenomenon occurs predominantly in female patients, presenting with a variety of ST-T segment changes and mildly elevated cardiac enzymes that mimic an acute coronary syndrome. The left ventricular dysfunction, typically showing a hyperkinetic basal region and an akinetic apical half of the ventricle, occurs in the absence of obstructed epicardial coronary arteries. The ventricular dysfunction usually resolves within weeks with a generally favorable prognosis. This phenomenon has similarities to that seen in patients with acute brain injury with regard to clinical presentation, pathology, and its reversible nature., Conclusions: Transient left ventricular dysfunction occurs in the absence of obstructive epicardial coronary artery disease. In its broadest sense, this phenomenon may encompass a range of disorders including left ventricular dysfunction after central nervous system injury.

Objectives: We sought to determine the incidence, clinical features, and risk factors for retroperitoneal hematoma (RPH) after percutaneous coronary intervention (PCI)., Background: Little is known about the clinical features, outcomes, and determinants of this serious complication in the contemporary era of PCI., Methods: A retrospective analysis yielded 26 cases of RPH out of 3,508 consecutive patients undergoing PCI between January 2000 and January 2004. Cases were compared with a randomly selected sample of 50 control subjects without RPH., Results: The incidence of RPH was 0.74%. Features of RPH included abdominal pain (42%), groin pain (46%), back pain (23%), diaphoresis (58%), bradycardia (31%), and hypotension (92%). The mean systolic blood pressure nadir was 75 mm Hg. The hematocrit dropped by 11.5 +/- 5.1 points from baseline in RPH patients, as compared with 2.3 +/- 3.3 points in controls (p < 0.0001). The mean hospital stay was longer in RPH patients (2.9 +/- 3.8 days vs. 1.7 +/- 1.5 days, p = 0.06). The following variables were found to be independent predictors of RPH: female gender (odds ratio [OR] 5.4, p = 0.005), low body surface area (BSA <1.73 m(2); OR 7.1, p = 0.008), and higher femoral artery puncture (OR 5.3, p = 0.013). There was no association between RPH and arterial sheath size, use of glycoprotein IIb/IIIa inhibitors, or deployment of a vascular closure device., Conclusions: Female gender, low BSA, and higher femoral artery puncture are significant risk factors for RPH. Awareness of the determinants and clinical features of RPH may aid in prevention, early recognition, and prompt treatment.

An emotionally-distressed, elderly Caucasian woman presented with chest pain and hypertension. Electrocardiogram showed inferior ST-segment elevation, and an urgent cardiac catheterization was performed. Coronary angiography revealed normal appearing coronary arteries; however, left ventriculography showed extensive left ventricular apical akinesis. The patient had a mild rise in cardiac enzyme levels indicative of myocardial injury. She was discharged after an uncomplicated in-hospital course. One month later, the left ventricular wall motion abnormality had improved. In this report, the authors discuss this compilation of findings known as tako-tsubo-like left ventricular dysfunction.

The effect of Trypanosomiasis on concentrations of plasma steroids and semen characteristics was studied in 24 dromedary bulls. Based upon the parasitological and serological diagnosis, 18 bulls were found infected with Trypanosoma evansi (Group 2) and six were found to be free from infection and served as controls (Group 1). The infected animals exhibited signs of anaemia indicated by the decrease of packed cell volume (PCV) and haemoglobin concentration (Hb), pale mucus membranes, weight loss, lethargy, weakness and dullness. However, five animals (27.8%) of the infected group revealed elevated rectal temperatures and three animals (16.7%) revealed testicular degeneration upon palpation of their scrotal contents. Concentrations of plasma oestradiol-17beta (86.5 +/- 8.6 pg/ml versus 232.5 +/- 74.4 pg/ml) and testosterone (4.8 +/- 0.7 ng/ml versus 2.7 +/- 1.5 ng/ml) were significantly different (P < 0.05) between the control and infected bulls. Evaluation of the semen collected by electroejaculation and evaluated by a computerized cell motion analyzer revealed normal semen characteristics in the control animals compared to deteriorated ones in the infected bulls. There were highly significant (P < 0.01) decreases in sperm count (12.2 +/- 1.3/ml versus 6.5 +/- 4.9 x 10(6)/ml), motility percentage (68.2 +/- 6.7% versus 27.4 +/-15.6%), percentage of live spermatozoa (73.2 +/- 8.3% versus 35.8 +/- 8.2%) and increases in percentage of morphological abnormalities (3.3 +/- 0.6% versus 15.9 +/- 1.0%) in the infected group. An examination of the plasma hormonal profiles and semen characteristics in the infected bulls indicated that altered Sertoli cell function due to formation of immune complexes in four bulls (Group 2A), pituitary dysfunction in six bulls (Group 2B), testicular degeneration in three bulls (Group 2C) and finally trypanotolerancy in five bulls (Group 2D) are possible factors responsible for poor semen characteristics and infertility induced by T. evansi infection in dromedary bulls.

Objective: Experimental evidence indicates that ATP-sensitive potassium (K(ATP)) channels regulate coronary blood flow (CBF). However, their contribution to human coronary metabolic vasodilation is unknown., Methods and Results: Seventeen patients (12 male, age 58+/-10 years) were studied. Coronary hemodynamics were assessed before and after K(ATP) channel inhibition with subselective intracoronary glibenclamide infused at 40 microg/min in an angiographically smooth coronary artery after successful percutaneous coronary intervention to another vessel. Metabolic vasodilation was induced by 2 minutes of rapid right ventricular pacing. Coronary blood velocity was measured with a Doppler guidewire and CBF calculated. The time course of hyperemia was recorded for 2 minutes after pacing, and hyperemic volume was estimated from the area under the flow-versus-time curve (AUC). Compared with vehicle infusion (0.9% saline), glibenclamide reduced resting CBF by 9% (P=0.04) and increased resting coronary vascular resistance (CVR) by 15% (P=0.03). Glibenclamide reduced pacing-induced peak CBF (50.8+/-6.8 versus 42.0+/-5.4 mL/min, P=0.001), peak CBF corrected for baseline flow (25.1+/-4.6 versus 17.6+/-3.1 mL/min, P=0.01), and increased minimum CVR (2.6+/-0.3 versus 3.1+/-0.3 mm Hg/mL per minute, P=0.002). Compared with vehicle, glibenclamide reduced total AUC at 2 minutes (3535+/-397 versus 3027+/-326 mL, P=0.001)., Conclusions: Vascular K(ATP) channels appear to be involved in functional coronary hyperemia after metabolic stimulation.

Background: Thermodilution coronary flow reserve (CFRthermo) is a new technique for invasively measuring coronary flow reserve (CFR) with a coronary pressure wire and is based on the ability of the pressure transducer to also measure temperature changes. Whether CFRthermo correlates well enough with absolute flow-derived CFR (CFRflow) to replace Doppler wire-derived CFR (CFRDoppler) remains unclear., Methods and Results: In an open-chest pig model, CFRthermo was measured in the left anterior descending (LAD) artery and compared with CFRDoppler and CFRflow, measured with an external flow probe placed around the LAD. In 9 pigs, CFR was measured simultaneously by all 3 means in the normal LAD and after creation of an epicardial LAD stenosis. To determine the added effect of microvascular disease, measurements of flow reserve were also performed after disruption of the coronary microcirculation with embolized microspheres. Intracoronary papaverine (20 mg) was used to induce hyperemia. In a total of 61 paired measurements, CFRthermo correlated strongly with the reference standard CFRflow (r=0.85, P<0.001). CFRDoppler correlated less well with CFRflow (r=0.72, P<0.001). Bland-Altman analysis showed a closer agreement between CFRthermo and CFRflow., Conclusions: CFRthermo correlates better with CFRflow than does CFRDoppler.

Background: A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking., Methods and Results: By using a coronary pressure wire and modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9+/-6.5 U to 25.9+/-14.4 U, P=0.002) and TMR (0.51+/-0.14 to 0.79+/-0.32 mm Hg x mL(-1) x min(-1), P=0.0001), as well as the % change in IMR (147+/-66%) and TMR (159+/-105%, P=NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR., Conclusions: Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.