Study of urinary leukotriene E4 in atopic dermatitis: relation to disease severity

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease prevalent in patients with a personal or family history of atopy. Cysteinyl leukotrienes (LTs) are inflammatory mediators which play a role in the pathogenesis of atopic diseases. Urinary leukotriene E4 (LTE4) has been used as an index of the whole body cysteinyl LTs production. Objective: This study was meant to evaluate the importance of LTs in atopic dermatitis (AD) and to study the correlation of urinary LTE4 with disease severity and some commonly altered parameters in AD. Methods: The study included 30 children and adolescents diagnosed to have atopic dermatitis. Ten age and sex matched healthy children and adolescents were enrolled for comparison. They were subjected to clinical evaluation and measurement of urinary LTE4, absolute eosinophilic count, serum IgE and IL-4 and IL-5 in peripheral blood mononuclear cell culture (PBMC) supernatant. The patients were categorized into mild (n=5), moderate (n=16) and severe (n=9) AD subgroups. Results: The study revealed a significant increase in absolute eosinophilic count, urinary LTE4, serum IgE and IL-4 and IL-5 in PBMC culture supernatant in the patients as compared to controls. Moreover, urinary LTE4 levels were significantly increased in moderate and severe cases of AD as compared to the control group, whereas mild cases had levels that were comparable to the controls. Urinary LTE4 levels were higher in severe (p < 0.01) and moderate cases (p < 0.05) when compared to mild cases. Significant positive correlations could be elicited between urinary LTE4 and PBMC IL-4, disease severity scale, absolute eosinophilic count and serum total IgE. However, urinary LTE4 could not be correlated statistically with PBMC IL-5. Conclusion: Elevation in urinary LTE4 excretion in AD patients was demonstrated reflecting increased production of cysteinyl LTs. Urinary LTE4 was correlated to clinical and laboratory markers of severity suggesting that it could be an easy, non invasive and objective prognostic test in AD. Trials of 5-lipoxygenase inhibitors and LT receptor antagonists as additional lines of therapy in AD could thus be suggested.Keywords: atopic dermatitis, urinary LTE4, IgE, IL-4, IL-5, eosinophilic countEgypt J Pediatr Allergy Immunol 2003; 1(2): 134-

Multicentre study of Wilm’s tumours treated by different therapeutic strategies in two different countries

Background and purpose According to the treatment of Wilm’s tumours, two different therapeutic strategies were established in the second half of the last century. Both National Wilm’s Tumour Study (NWTS) group and the International Society of Paediatric Oncology (SIOP) have helped to improve the clinical management and outcome of patients with Wilm’s tumours. In this study, we compared three groups of patients with Wilm’s tumours from different racial backgrounds and therapeutic strategies.Patients and methods A clinicopathological review was carried out for 40 patients treated at Kyushu University Hospital in Japan from 1960 to 2006 according to NWTS, 79 patients treated at the South Egypt Cancer Institute from 2002 to 2009 according to the SIOP protocol and 33 patients treated at the Pediatric Surgery Department of Assiut University Hospital from 2000 to 2009 according to the NWTS protocol.Results In the Kyushu University group, a favourable histology was diagnosed in 80% of patients and an unfavourable histology in 20% of patients. The distribution of the clinical stage was as follows: I = 40%, II =22.5%, III = 22.5%, IV = 7.5% and V = 7.5%. The 5-year overall survival was 82.5%, with the 5-year stage-related survival as follows: I= 93.7%, II =83.3%, III= 62.5%, IV = 33.3% and V = 100%. In the South Egypt Cancer Institute group, favourable histology was diagnosed in 89.9% of patients, unfavourable histology in 8.8% of patients and benign disease in 1.3% of patients. The distribution of the clinical stage (before and after chemotherapy) was as follows: I = 25.3%-50%, II= 19%-20%, III= 35.4-15%, IV = 12.5%-5% and V = 7.6%-7.6%. No case of intraoperative tumour rupture was recorded. The overall 5-year survival rate of 84% with a 5-year stage-related survival was as follows: I= 92%, II =80%, III= 50%, IV = 31% and V = 30%. In the Assiut University group, a favourable histology was diagnosed in 79% of patients and an unfavourable histology in 9% of patients. The distribution of the clinical stage was as follows: I= 39.4%, II =21.2%, III = 21.2%, IV = 12% and V =6%. The overall 5-year survival rate was 77% and the 5-year stage-related survival was as follows: I= 85%, II= 75%, III = 52%, IV = 33% and V = 33%.Conclusion The Egyptian patients with Wilm’s tumour presented at a younger age and had less incidence of an unfavourable histology compared with Japanese patients. Preoperative chemotherapy increased the rate of stage I disease and decreased the incidence of intraoperative tumour rupture and relapse. However, there was a possibility that chemotherapy had been administered in the case of benign disease. Keywords: intraoperative tumour rupture, NWTS, SIOP, Wilm’s tumou

Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides

<p>Abstract</p> <p>Background</p> <p>The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.</p> <p>Results</p> <p>EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP.</p> <p>On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.</p> <p>Conclusion</p> <p>DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress.</p

Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil inmice

Background: Clove oil of Eugenia caryophyllata (Myrtaceae) is a light yellowish fluid obtained from dried flower buds. Clove oil is used traditionally to relieve toothache.Aim: The aim of the present work was to study the anti-inflammatory, antinociceptive and antipyretic potential of clove oil in mice.Methods: Analgesic activity was examined using acetic-acid-induced abdominal constrictions and the hot plate test. Carrageenan-induced paw edema and brewer’s-yeast-induced pyrexia were used to investigate the anti-inflammatory activity and the antipyretic effects, respectively. The oil was administered intraperitoneally (i.p.) at a dose of 33 mg/kg body weight and the effects were compared with reference drugs.Results: In the antinociceptive test, mice treated with clove oil exhibited significantly decreased acetic-acidinducedwrithing movements by a maximum of 87.7% (p&lt;0.01) compared with a decrease of 77.7% (p&lt;0.01) in response to aspirin injection (100 mg/kg, intraperitoneal, i.p.). Similarly, in the hot plate test, clove oil significantly increased the reaction latency to pain after 60 min by 82.3% (p&lt;0.05) compared with morphine value of 91.7% (p&lt;0.01). In addition, clove oil and indomethacin produced anti-inflammatory effects, as demonstrated by respectively 50.6% (p&lt;0.05) and 70.4% (p&lt;0.01) inhibition of mouse paw edema induced by carrageenan. Furthermore, clove oil significantly attenuated the hyperthermia induced by yeast at ΔT-max by 2.7oC (p&lt;0.001), and time of peak effects was 30-180 min compared with a paracetamol value ΔT-max of 3.2oC (p&lt;0.001). The estimated i.p. LD50 of clove oil was 161.9 mg/kg. Phytochemical screening of the oil showed the presence of eugenol.Conclusion: The present findings demonstrate the potential pharmacological properties of clove oil and provide further a support for its reported use in folk medicine.Keywords: Eugenia caryophyllata; clove oil; eugenol; antinociceptive; anti-inflammatory; antipyretic; mic

A Proposed Educational Model to Improve the Operations of Knowledge-Exchange between MOE and Higher Education Institutions in Jordan

هدفت الدراسة إلى بناء أنموذج تربوي مقترح لتحسين عمليات تبادل المعرفة بين وزارة التّربية والتّعليم ومؤسسات التّعليم العالي في الأردنّ، وتكونت عينة الدراسة من (301) من القادة التربويين، منهم (158) عضو هيئة تدريس من العاملين في كلية العلوم التربوية بالجامعة الأردنية، وكلية التّربية بجامعة اليرموك، و(143) من العاملين في مركز وزارة التّربية والتّعليم في الأردنّ للعام الدراسي 2016/ 2017م. ولتحقيق هدف الدراسة قام الباحثان ببناء استبانة تكونت من (88) فقرة بعد التحقق من دلالات صدقها وثباتها، ولتحليل البيانات استُخدمت المتوسطات الحسابية، والانحرافات المعيارية. أظهرت نتائج الدراسة تقديرات متوسطة لدرجة ممارسة عمليات تبادل المعرفة بين وزارة التّربية والتّعليم ومؤسسات التّعليم العالي في الأردن من وجهة نظر القادة التربويين، وكذلك بينت النتائج أن درجة تقدير القادة التربويين للمعوقات التي توجه عمليات تبادل المعرفة كانت متوسطة، وتوصلت الدراسة إلى بناء أنموذج لتحسين عمليات تبادل المعرفة بين وزارة التّربية والتّعليم ومؤسسات التّعليم العالي في الأردن، والتي أوصت باعتماده وتطبيقه في الأردن وتقييمه بشكل مستمر. الكلمات المفتاحية: الأنموذج، عمليات تبادل المعرفة، درجة الممارسة، المعوقات، الجامعات الأردنية، وزارة التّربية والتّعليم الأردنية.The purpose of this study was to build a proposed educational model for improving knowledge-exchange processes between the Ministry of Education and Higher Education institutions in Jordan. The sample of the study consisted of (301) educational leaders: (158) academic staff members from the Faculty of Educational Sciences – University of Jordan – and the Faculty of Education in Yarmouk University; and (143) members from the center of Jordanian Ministry of Education for the academic year 2016/2017. To achieve the aims of the study, the researcher built a questionnaire, consisting of (88) items as tool for collecting data. The research tool was checked for its validity and reliability semantics. To analyze the data, means and standard deviation were used. The results of the study showed that the educational leaders rated the degree of practicing knowledge-exchange processes between Jordanian Ministry of Education and Higher Education institutions in Jordan as (moderate). Also, they rated the obstacles that face knowledge-exchange processes as (moderate). The study concluded with a proposed educational model for improving knowledge-exchange processes between the Ministry of Education and Higher Education institutions in Jordan, and recommended to be approved and applied in Jordan. Keywords: A Proposed educational model, Knowledge-exchange processes, Practicing degree, Obstacles, Jordanian Universities, Jordanian Ministry of Educatio

A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania

Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and species specific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1-2 years, those aged 3 and 4-5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem

Improving motivation among primary health care workers in Tanzania: a health worker perspective

In Tanzania access to urban and rural primary health care is relatively widespread, yet there is evidence of considerable bypassing of services; questions have been raised about how to improve functionality. The aim of this study was to explore the experiences of health workers working in the primary health care facilities in Kilimanjaro Region, Tanzania, in terms of their motivation to work, satisfaction and frustration, and to identify areas for sustainable improvement to the services they provide. The primary issues arising pertain to complexities of multitasking in an environment of staff shortages, a desire for more structured and supportive supervision from managers, and improved transparency in career development opportunities. Further, suggestions were made for inter-facility exchanges, particularly on commonly referred cases. The discussion highlights the context of some of the problems identified in the results and suggests that some of the preferences presented by the health workers be discussed at policy level with a view to adding value to most services with minimum additional resources

Acute febrile illness is associated with Rickettsia spp infection in dogs

BACKGROUND: Rickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. METHODS: Dogs from southern Italy with acute fever (n = 99) were compared with case–control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. RESULTS: The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank®, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. CONCLUSIONS: This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

&lt;p&gt;Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.&lt;/p&gt; &lt;p&gt;Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.&lt;/p&gt; &lt;p&gt;Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.&lt;/p&gt