Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats?

The aims of the present work were to study the effects of chronic NO inhibition on liver cirrhosis and to analyze its relationship with liver and kidney damage markers. Two inhibitors of NO synthesis (inducible NO synthase (iNOS) inhibitor, aminoguanidine (AG), and nonselective NOS inhibitor, L-nitroarginine methyl ester (L-NAME)) were administered for 6 weeks to bile duct ligated (BDL) rats 3 days after surgery. The present study showed that BDL was associated with liver injury and renal impairment. BDL increased liver NO content and myeloperoxidase (MPO) activity. This was corroborated by increased oxidative stress, TNF-α, TGF-1β, and MMP-13 genes overexpression. Although both drugs reduced NO synthesis and TNF-α gene overexpression, only AG improved renal dysfunction and liver damage and reduced liver oxidative stress. However, L-NAME exacerbated liver and renal dysfunction. Both drugs failed to modulate TGF-1β and MMP-13 genes overexpression. In conclusion, inhibition of NO production by constitutive nitric oxide synthase (cNOS) plays a crucial role in liver injury and renal dysfunction while inhibition of iNOS by AG has beneficial effect. TNF-α is not the main cytokine responsible for liver injury in BDL model. Nitric oxide inhibition did not stop the progression of cholestatic liver damage

Assessment of Quality of Life among Beta-Thalassemia Major Patients Attending the Hematology Outpatient Clinics at Cairo University Hospital

AIM: This paper aimed at assessing the quality of life (QoL) among beta (β)-thalassemia major patients using the short-form-36questionnaire (SF-36) and determining the factors associated with it. METHODS: A cross-sectional study was conducted among β-thalassemia major patients who were attending the hematology outpatient clinic at Cairo University Hospital using the consecutive sampling technique. Data were collected between October 2016 and March 2017. The QoL was assessed for patients aged ≥17 years. During the study period, a total number of 112 patients were included for participation. RESULTS: The mean age of the studied group was 18.32 ± 1.33 years. Most of the included patients (93.63%) had 1 monthly blood transfusion. The mean total score of SF-36 was 44.90 ± 7.54. Among the QoL domains of the studied patients, the “general health perception” domain was the most affected one with a mean score of (add the value of the score here), while the “vitality” domain was the least affected one. No statistically significant difference was reported between males and females regarding different QoL domains except for the “vitality” domain which mean score was significantly higher in males compared to females (p = 0.05). The age at onset of the disease and at first blood transfusion was the most documented factors to be positively correlated with the QoL among the studied patients. CONCLUSION: This study revealed that the QoL in thalassemia major patients is compromised. QoL assessment should be performed for all thalassemia patients to determine and implement the necessary interventions that focus on the affected domains

Relation of Advanced Glycation End Products and Primary Open Angle Glaucoma Progression

The purpose of this paper is to investigate the relation between oxidative stress and advanced glycation end products in patients suffering from different stages primary open angle glaucoma (POAG) and complications of glaucoma progression. Forty five patients suffering from POAG classified into three stages; mild, moderate and advanced as well as fifteen healthy "non- diabetic subjects" (age and sex matched healthy controls) were selected from the outpatient clinic in the Research Institute of Ophthalmology (RIO) Giza Egypt.nitric oxide (NO), malondialdehyde (MDA), ascorbic acid (vitamin C), α-tocopherol (vitamin E), catalase activity (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and advanced glycation end products (AGEs) were estimated in all studied groups. A significant increase in MDA, NO and AGEs levels was detected in mild, moderate and advanced glaucoma compared to control, also significant decreases in vitamin C, vitamin E, GSH, and SOD activities were found in mild, moderate and advanced glaucoma compared to control. No significant change was found in catalase activity in all groups compared to control. Statistical significant positive correlations were found between intra ocular pressure (IOP) and disease severity. this study clearly demonstrated increased accumulation of AGEs, lipid peroxidation products along with impairment of the antioxidant status in patients with primary open angle glaucoma.We suggest that AGEs measurement could be used as a diagnostic marker in primary screening programs for diagnosis and prediction of the development and progression of glaucoma

Genotyping of carbapenem resistant Acinetobacter baumannii isolated from Egyptian patients

Acinetobacter baumannii has recently been known as a major cause of hospital- and community-acquired infections. Carbapenem resistant A. baumanni (CRAB) has been recorded to be resistant to nearly all antibiotics, including the last resort antibiotics; carbapenems. This study aimed to detect the carbapenem resistance levels and mechanisms, in addition to the genotyping of A. baumanni in Upper Egypt. About 200 clinical samples were collected from different wards of Sohag University Hospital, Egypt, from which 20 A. baumannii isolates were recovered and then identified using conventional methods and Polymerase Chain Reaction (PCR). Antibiotic sensitivity testing was carried out using the Disk diffusion method, followed by PCR testing of the common carbapenemase-encoding genes, including OXA-51, OXA-58, KPC, GES, IMP, NDM, VIM, SIM, and GIM. Genotyping was performed using the Enterobacterial Repetitive Intergenic Consensus-Polymerase chain reaction (ERIC-PCR). About 85 % of A. baumannii strains were multidrug resistant (MDR), and high rate of Extreme drug resistant (XDR) A. baumannii (70 %) was detected. Carbapenem resistance was detected in 65 % of A. baumannii isolates, 70.58 % of MDR isolates, and 85.7 % of XDR isolates, respectively. Carbapenemase- encoding genes, including blaOXA-51, VIM, NDM, and GES, were detected in 100 %, 100 %, 76.9 2 % and 76.92 % of the carbapenem resistant A. baumannii (CRAB) isolates, respectively. The blaIMP and blaKPC genes had lower prevalence rates of 15.38 % and 30.77 %; respectively, whereas the SIM, GIM, and OXA-58 genes were not detected in any of the tested A. baumanni isolates. All of the MDR isolates carried three or more the carbapenemases encoding genes, and 85.7 % of the XDR isolates carried four or more of the carbapenemase-encoding genes. The dendrogram constructed from the ERIC-PCR results showed that the A. baumannii isolates were divided into three different clusters

Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata

Background and Aim: Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Materials and Methods: Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2–3 W, 80–120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. Results: C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47–30.98 nm and 18.83–38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7–17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. Conclusion: C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs

Insecticide resistance in the sand fly, Phlebotomus papatasi from Khartoum State, Sudan

<p>Abstract</p> <p>Background</p> <p><it>Phlebotomus papatasi </it>the vector of cutaneous leishmaniasis (CL) is the most widely spread sand fly in Sudan. No data has previously been collected on insecticide susceptibility and/or resistance of this vector, and a first study to establish a baseline data is reported here.</p> <p>Methods</p> <p>Sand flies were collected from Surogia village, (Khartoum State), Rahad Game Reserve (eastern Sudan) and White Nile area (Central Sudan) using light traps. Sand flies were reared in the Tropical Medicine Research Institute laboratory. The insecticide susceptibility status of first progeny (F1) of <it>P. papatasi </it>of each population was tested using WHO insecticide kits. Also, <it>P. papatasi </it>specimens from Surogia village and Rahad Game Reserve were assayed for activities of enzyme systems involved in insecticide resistance (acetylcholinesterase (AChE), non-specific carboxylesterases (EST), glutathione-S-transferases (GSTs) and cytochrome p450 monooxygenases (Cyt p450).</p> <p>Results</p> <p>Populations of <it>P. papatasi </it>from White Nile and Rahad Game Reserve were sensitive to dichlorodiphenyltrichloroethane (DDT), permethrin, malathion, and propoxur. However, the <it>P. papatasi </it>population from Surogia village was sensitive to DDT and permethrin but highly resistant to malathion and propoxur. Furthermore, <it>P. papatasi </it>of Surogia village had significantly higher insecticide detoxification enzyme activity than of those of Rahad Game Reserve. The sand fly population in Surogia displayed high AChE activity and only three specimens had elevated levels for EST and GST.</p> <p>Conclusions</p> <p>The study provided evidence for malathion and propoxur resistance in the sand fly population of Surogia village, which probably resulted from anti-malarial control activities carried out in the area during the past 50 years.</p

Androgen-Regulated Expression of Arginase 1, Arginase 2 and Interleukin-8 in Human Prostate Cancer

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer in North American men. Androgen-deprivation therapy (ADT) accentuates the infiltration of immune cells within the prostate. However, the immunosuppressive pathways regulated by androgens in PCa are not well characterized. Arginase 2 (ARG2) expression by PCa cells leads to a reduced activation of tumor-specific T cells. Our hypothesis was that androgens could regulate the expression of ARG2 by PCa cells. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we demonstrate that both ARG1 and ARG2 are expressed by hormone-sensitive (HS) and hormone-refractory (HR) PCa cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 was more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 were overexpressed. The regulation of arginase expression following androgen stimulation was dependent on the androgen receptor (AR), as a siRNA treatment targeting the AR inhibited both ARG1 and ARG2 overexpression. This observation was correlated in vivo in patients by immunohistochemistry. Patients treated by ADT prior to surgery had lower ARG2 expression in both non-malignant and malignant tissues. Furthermore, ARG1 and ARG2 were enzymatically active and their decreased expression by siRNA resulted in reduced overall arginase activity and l-arginine metabolism. The decreased ARG1 and ARG2 expression also translated with diminished LNCaP cells cell growth and increased PBMC activation following exposure to LNCaP cells conditioned media. Finally, we found that interleukin-8 (IL-8) was also upregulated following androgen stimulation and that it directly increased the expression of ARG1 and ARG2 in the absence of androgens. CONCLUSION/SIGNIFICANCE: Our data provides the first detailed in vitro and in vivo account of an androgen-regulated immunosuppressive pathway in human PCa through the expression of ARG1, ARG2 and IL-8

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

[Rapport]

GR-53 2057 ; SB ISIC. Consultable sur demande à la bibliothèque de l'EPFL / Offered in consultation at the EPFL librar