Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model

In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine-depleted rats, IFO induced dramatic increase in serum creatinine, BUN, CK-MB, LDH, carnitine clearance and intramitochondrial acetyl-CoA/CoA-SH, as well as progressive reduction in total carnitine and ATP in cardiac tissues. Interestingly, PLC supplementation completely reversed the biochemical changes-induced by IFO to the control values. In conclusion, data from the present study suggest that: Carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, constitute risk factors and should be viewed as mechanisms during development of IFO-induced cardiotoxicity. Carnitine supplementation, using PLC, prevents the development of IFO-induced cardiotoxicity through antioxidant signalling and improving mitochondrial function

THE EFFECT OF THE EXOGENOUS GIBBERELLIC ACID ON TWO SALT STRESSED BARLEY CULTIVARS

An alternative strategy to ameliorate salt stress could be to use exogenous application of plant growth regulators. The present investigation was carried out to study the effect of exogenous application of GA3 on germination, some growth parameters, protein banding pattern, nucleic acids content and some minerals of salt stressed two cultivars of barley. The grains of both cultivars Giza 126 and 123 were individually pre emergence treated with different concentrations of NaCl or mixture of NaCl and GA3 for 7 days. The results of germination percentage revealed that cv. Giza 123 had higher response to the interaction between salinity and GA3 than cv. Giza 126. The morphological characters revealed inhibition in all plant growth parameters by salinity stress and this inhibition was significantly alleviated after treatment with GA3. The protein electrophoresis of seedlings of cv. Giza 123 induced formation of unique newly protein bands including certain units may acting as protein receptors for gibberellins (M.W. 71.41 kDa). In addition, the DNA and RNA content of cv. Giza 123 showed its priority to the interaction between salinity and GA3. Regarding to minerals the data showed that cv. Giza 123 had the ability to discard salts and prevent the accumulation of them in its tissues especially Na+, k+ and Ca+2 elements. cv. Giza 123 seedlings could overcome the inimical effects of salt stress whereas cv. Giza 126 seedlings appeared to have an attenuated potential to do so resulting in an efficient tolerance of cv. Giza 123 seedlings

Penetration enhancers in proniosomes as a new strategy for enhanced transdermal drug delivery

AbstractThe aim of this work is to investigate penetration enhancers in proniosomes as a transdermal delivery system for nisoldipine. This was performed with the goal of optimising the composition of proniosomes as transdermal drug delivery systems. Plain proniosomes comprising sorbitan monostearate, cholesterol, ethanol and a small quantity of water were initially prepared. Subsequently, proniosomes containing lecithin or skin penetration enhancers were prepared and evaluated for transdermal delivery of nisoldipine. The plain proniosomes significantly enhanced the transdermal flux of nisoldipine to reach 12.18μgcm−2h−1 compared with a saturated aqueous drug solution which delivered the drug at a rate of 0.46μgcm−2h−1. Incorporation of lecithin into such proniosomes increased the drug flux to reach a value of 28.51μgcm−2h−1. This increase can be attributed to the penetration enhancing effect of lecithin fatty acid components. Replacing lecithin oleic acid (OA) produced proniosomes of comparable efficacy to the lecithin containing system. The transdermal drug flux increased further after incorporation of propylene glycol into the OA based proniosomes. Similarly, incorporation of isopropyl myristate into plain proniosomes increased drug flux. The study introduced enhanced proniosomes as a promising transdermal delivery carrier and highlighted the role of penetration enhancing mechanisms in enhanced proniosomal skin delivery. The study opened the way for another line of optimisation of niosome proconcentrates

CHOLESTATIC LIVER FIBROSIS IN A RAT MODEL OF BILE DUCT LIGATION: EVALUATING BIOCHEMICAL VERSUS HISTOPATHOLOGICAL CHANGES

Objective: Bile duct ligation (BDL), chronic liver injury model, was extensively used in studying mechanisms of fibrogenesis and antifibrotic agents. Considering the liver regenerative capacity and the diverse results from BDL, the present study aimed to evaluate the biochemical and histopathological changes over 10 weeks following BDL assessing if BDL-induced changes remain in a deterioration state or improve at a certain stage.Methods: Sham operation and BDL were conducted in Male Wistar rats. Serum AST, ALT, total bilirubin and albumin and hepatic hydroxyproline (HYP), reduced glutathione (GSH) and malondialdehyde (MDA) were measured in sham-operated (n=3) and BDL-rats (n=6) at 0, 1, 2, 4, 6, 8 and 10 weeks following operation. Liver tissue was also processed for histopathological analysis (H&E and Sirus red staining).Results: Progressive liver injury (H&E) and collagen deposition (Sirus red and HYP) in BDL-rats were observed starting from the first week post-operation and reached their maximum with early signs of cirrhosis on the 10th week of BDL. Severe and sustained cholestatic injury appeared in 2 weeks (increased ALT, AST, bilirubin along with decreased albumin (P<0.001) compared to sham-operated rats). AST peaked on first week, however, bilirubin, ALT and MDA peaked on the 4th week (P<0.001) then gradually decreased compared to their peaks.Conclusion: The relative improvement in liver function/cholestasis following their peaks in BDL model despite progression of fibrosis and hepatic injury require investigators using this model to consider not only biochemical, but also histopathological findings to guarantee an accurate interpretation of their results.Â

Flame Retardant and Mechanical Properties of Modified Paper Using Inorganic Salts for Packaging Applications

The paper sheet prepared from unbleached rice straw containing different concentration of inorganic salts, that work as flame retardant additives (Lithium hydroxide one hydrate (LiOH.1H2O), Magnesium hydroxide (Mg (OH)2. 15H2O), aluminum sulphate (Al2(SO4)3) and calcium carbonate (CaCO3)) were investigated using horizontal burning test against flame retardant. Also, the prepared paper sheets were characterized using scanning electron microscope (SEM), thermal gravimetric analysis (TGA) and Infrared spectroscopy (IR). Furthermore, the water absorption was determined. In addition, the mechanical properties (breaking length, tear factor and burst factor) of the prepared paper sheet were evaluated. Correspondingly, the physical (structure and mechanical) properties of the prepared paper sheet were enhanced in terms of tensile, tear factor and water absorption. Also, delaying firing process will help in protecting the materials from burning, saving many of economic effect. So the prepared paper sheet can be used for different industrial applications especially in packaging applications

New Algorithm for Drawings of 3-Planar Graphs

Graphs arise in a natural way in many applications, together with the need to be drawn. Except for very small instances, drawing a graph by hand becomes a very complex task, which must be performed by automatic tools. The field of graph drawing is concerned with finding algorithms to draw graph in an aesthetically pleasant way, based upon a certain number of aesthetic criteria that define what a good drawing, (synonyms: diagrams, pictures, layouts), of a graph should be. This problem can be found in many such as in the computer networks, data networks, class inter-relationship diagrams in object oriented databases and object oriented programs, visual programming interfaces, database design systems, software engineering…etc. Given a plane graph G, we wish to find a drawing of G in the plane such that the vertices of G are represented as grid points, and the edges are represented as straight-line segments between their endpoints without any edge-intersection. Such drawings are called planar straight-line drawings of G. An additional objective is to minimize the area of the rectangular grid in which G is drawn. In this paper we introduce a new algorithms that finds an embedding of 3-planar graph. Keywords: 3- Planar Graph; Graph Drawing; drawing on grid

Effects of Preoperative Sublingual Misoprostol on Uterine Tone during Isoflurane Anesthesia for Cesarean Section

SummaryBackground and objectivesMisoprostol would reduce the uterine bleeding after cesarean delivery without harmful effects on either mother or baby. We aimed to evaluate the effects of preoperative misoprostol on maternal blood loss, uterine tone, and the need for additional oxytocin after cesarean delivery under isoflurane anesthesia.MethodsAfter ethical approval, 366 patients scheduled for elective cesarean delivery were randomly allocated to receive either sublingual misoprostol 400μg (n=179) or placebo tablet (n=187) after intubation. Anesthesia was maintained with 0.5–0.7 MAC isoflurane with nitrous oxide. All patients received intravenous infusion of 10IU of oxytocin after placental delivery. Perioperative estimated blood loss, uterine tone, need for supplementary oxytocin, hematocrit, Apgar scores at 1 and 5 min and adverse effects were recorded.ResultsAfter induction, patients receiving sublingual misoprostol had significant less perioperative estimated blood loss (202±383.1 vs. 708±204.3mL, p<0.001), need for oxytocin (p<0.001), higher hematocrit levels (p<0.001) and uterine tone (p<0.02). The incidence of shivering was higher in the misoprostol group (p=0.04). There were no differences between the two groups as regarding Apgar scores, nausea and vomiting, gastrointestinal disturbances and pyrexia.ConclusionPreoperative administration of sublingual misoprostol 400μg is safe and effective in attenuating the maternal bleeding and uterine atony from isoflurane anesthesia for cesarean delivery

Shear Performance of GFRP Reinforced Concrete Beams with Seawater and Chopped Fiber

This paper reports an experimental study on the behavior and shear strength of concrete beams reinforced with longitudinal GFRP bars mixed with sea water. In order to evaluate how much concrete contributes to shear resistance, seven beams were tested in bending. Similar in size and concrete strength, the beams were longitudinally reinforced with glass fiber-reinforced polymer bars; however, they did not even have shear reinforcement. The beams, which measured 3,100 mm in length, 400 mm in depth, and 200 mm in width, were conducted and tested up to failure. The test variables were longitudinal reinforcement ratios (1.0, 1.4, and 2.0%), chopped fiber content (0, 0.5, 2, and 3 kg/m3), and mixing water type (freshwater and seawater). The test findings showed that increasing the reinforcement ratio increased the neutral-axis depth and allowed the formation of more closely spaced fractures while decreasing the loss of flexural stiffness after cracking. By increasing the area of concrete in compression, this in turn enhances the contribution of aggregate interlock as well as the contribution of uncracked concrete. Furthermore, increasing the reinforcement ratio improves the dowel action, which reduces the tensile stresses that are created in the concrete around it. Doi: 10.28991/CEJ-2023-09-04-05 Full Text: PD

Role of magnetic resonance imaging in loco-regional evaluation of cancer rectum, pre and post neoadjuvant therapy

The high rate of local recurrence is considered the major concern and challenge regarding the surgical treatment of cancer rectum. The target of use of pre-operative neoadjuvant therapy is reducing tumour size and improving its resectability in order to reduce local recurrence risk and improve survival rates.Plans for management and treatment of locally advanced rectal cancer showed clear changes after use of neoadjuvant therapy. This in turn necessitates accurate evaluation of the tumour parameters before and after use of combined chemotherapy and radiation therapy (CRT).Aim of study is to assess the initial stage of cancer rectum then its response to neoadjuvant therapy using MRI, prior to operative interference. This is followed by post-operative histo-pathological data correlation.Methods: This study was conducted on 50 patients. All patients were examined by high-resolution T2- weighted images. Turbo-spin-echo sequences taken in sagittal plane, axial plane perpendicular to tumor axis and coronal plane parallel to tumor axis or anal canal. All are according to tumor height. Diffusion weighted images (DWI) performed in all cases.Results: Following neoadjuvant therapy, down-staging was detected in this study in more than 90% of patients regarding the T2 signal and apparent diffusion coefficient (ADC) value of the tumour, also status of depth of involvement of meso-rectal fascia (MRF), circumferential resection margin (CRM), extramural vascular invasion (EMVI) and nodal involvement.Conclusion: Pre-operative MRI in cancer rectum is irreplaceable to assess initial staging and postneoadjuvant therapy response thus improving surgical results.Keywords:  MRI, CRT, DWI, ADC, MRF, CRM, EMV