ASSESSING THE BIOACTIVITY AND ANTIOXIDATIVE PROPERTIES OF SOME COMPOUNDS ISOLATED FROM ABUTILON HIRTUM (LAM.)

ABSTRACTObjectives: The present study on the methanol extract of Abutilon hirtum (Lam.) [Malvaceae] afforded ten compounds. Findings from this assessmentindicated that A. hirtum leaves possessed vast potential as medicinal product especially in liver cancer treatment.Methods: Dried-powdered leaves were boiled under reflux in 10 L of petroleum ether for 8 hrs. After filtration, the solvent was evaporated; afforded15 g of petroleum ether extract followed by boiling with reflux for 8 hrs with chloroform, then filtration and the residue was evaporated to give 34 gchloroform extract. Ethyl acetate was added and refluxed for 8 hrs, then filtration and evaporation to give 31 g ethyl acetate extract. Finally the leaveswere refluxed with 10 L of 85 % aqueous MeOH, after cooling, the solution was filtered and evaporated and the residue was 210 g methanol extractthen the residue was dissolved in de-ionized water (250 ml), then the salt was removed by adding excess methanol solution (2.5 L), and finally filtered.The cytotoxicity of the isolated compounds was evaluated towards HepG2 liver-carcinoma cell line using MTT assay, the antimicrobial activity wastested using the Disc agar plate method and the total antioxidant capacity was determined according to phosphomolybdenum method.Results: The isolated compounds identified as methyl gallate, cuneataside E, bergapten, gallic acid, ellagic acid, epigallocatechin-3-O-gallate,kaempferol-3-O-α-L-rhamnoside, benzyl-1-O-β-D-glucopyranoside, 2(4-hydroxyphenyl)ethyl-O-β-D-glucopyranoside and β-sitosterol. All the isolatedcompounds are known; but they were isolated from Abutilon hirtum for the first time.Conclusion: This report may serve as a footprint concerning the biological and pharmacological activities of A. hirtum leaves.Keywords: Abutilon hirtum, Malvaceae, HepG2, Phenolics, Antioxidant.Â

Implementation and Evaluation of Antimicrobial Stewardship Program in Medical ICU in Cairo University Specialized Pediatric Hospital

BACKGROUND: High antibiotics use in pediatric intensive care units (PICUs) results in antibiotic resistance, the unfavorable clinical outcome of patients, increase the length of hospital stay, and drug expenditure. AIM: This study aimed at setting clinical guidelines customized according to local diseases epidemiology and local cumulative antimicrobial susceptibility, implementing, and evaluating the Antimicrobial Stewardship Program (ASP) effect in; optimizing antibiotics use, decreasing antibiotics expenditure, decreasing the length of therapy and stay in hospitals, and improving patients’ clinical outcomes. METHODS: A prospective study was conducted at a PICU of the Specialized Pediatric Hospital, Cairo University. Facility-specific guidelines were set, and the ASP was implemented and evaluated through the following indicators; adherence of physicians to the guidelines, ASP recommendations and acceptance of them, the rate of mortality, length of stay, drug costs, antibiotics days of therapy, and length of therapy. RESULTS: The adherence to the ASP guidelines was positively correlated to the patient’s clinical outcome (p = 0.018). In post ASP period, the average length of stay and the length of therapy significantly decreased (p = 0.047, p = 0.001, respectively), the rate of adherence to the ASP guidelines was (91.9%), the days of therapy of ceftazidime, ceftriaxone, and amikacin decreased significantly (p = 0.041, p = 0.026, p = 0.004, respectively). The most common ASP recommendation was drug schedule/frequency change (26.1%) followed by drug discontinuation (17.8%) and the most common antibiotic required intervention was ampicillin-sulbactam (21.6%). CONCLUSION: The antimicrobial stewardship is very effective in optimizing antibiotics use and leads to favorable outcomes in terms of decreased length of therapy, hospital stay, and mortality rate of the patients

Synthesis and antimicrobial activities of some novel bis-pyrazole derivatives containing a hydrophosphoryl unit

Vilsmeier-Haack reaction conditions were applied on some methyl ketone aryl phosphonicdihydrazones to yield some interesting bis-pyrazole derivatives containing a hydro-phosphoryl unit. Bis-{4-formyl-3-aryl-1H-pyrazol-1-yl}phosphine oxides (4a,b) were condensed with some nucleophiles such as aniline, phenacyltriphenylphosphonium bromide and 4-phenylthiosemicarbazide followed by treatment with thioglycolic acid, diethyl phosphite and/or acetic anhydride to yield a novel class of bis-pyrazoles containing sulfur and phosphorus derivatives. Most of the newly synthesized compounds were evaluated for their in vitro antimicrobial activities

CXCL16 and oxLDL are induced in the onset of diabetic nephropathy

Diabetic nephropathy (DN) is a major cause of end-stage renal failure worldwide. Oxidative stress has been reported to be a major culprit of the disease and increased oxidized low density lipoprotein (oxLDL) immune complexes were found in patients with DN. In this study we present evidence, that CXCL16 is the main receptor in human podocytes mediating the uptake of oxLDL. In contrast, in primary tubular cells CD36 was mainly involved in the uptake of oxLDL. We further demonstrate that oxLDL down-regulated α3-integrin expression and increased the production of fibronectin in human podocytes. In addition, oxLDL uptake induced the production of reactive oxygen species (ROS) in human podocytes. Inhibition of oxLDL uptake by CXCL16 blocking antibodies abrogated the fibronectin and ROS production and restored α3 integrin expression in human podocytes. Furthermore we present evidence that hyperglycaemic conditions increased CXCL16 and reduced ADAM10 expression in podocytes. Importantly, in streptozotocin-induced diabetic mice an early induction of CXCL16 was accompanied by higher levels of oxLDL. Finally immunofluorescence analysis in biopsies of patients with DN revealed increased glomerular CXCL16 expression, which was paralleled by high levels of oxLDL. In summary, regulation of CXCL16, ADAM10 and oxLDL expression may be an early event in the onset of DN and therefore all three proteins may represent potential new targets for diagnosis and therapeutic intervention in DN

EXTRACTION, ISOLATION, AND CHARACTERIZATION OF BIOACTIVE COMPOUNDS AND ESSENTIAL OIL FROM SYZYGIUM JAMBOS

Objectives: Over the past few decades, phenolic compounds become important due to it has been associated with protection against different diseasesand sensory point of vision. Hence, at the present study, there has been a growing interest to carry out structural elucidation and characterization ofthe pure isolates from Syzygium jambos.Methods: S. jambos dried powder leaves were extracted by soaking in 85% methanol solvent at room temperature 25±2°C. The antioxidative activityof the isolates was assessed according to 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and phosphomolybdenum assays.Results: A total of 8 compounds were isolated from the n-butanol extract of S. jambos (Family Myrtaceae) plant, they were identified as quercetin-3-O-rutinoside (1), prenylbenzoic acid 4-β-D-glucoside (2), morolic acid 3-O-caffeate (3), 5,4'-dihydroxy, 7-methoxy, 6-methyl-flavone (4),3,4,5-trihydroxybenzoic acid (5), quercetin (6), isoetin-7-O-β-D-glucopyranoside (7), and (4'-hydroxy-3'-methoxyphenol-β-D-[6-O-(4â€-hydroxy-3â€,5â€-dimethoxylbenzoate)] glucopyranoside) (8). Compounds 5 and 6 showed the most radical scavengers among the tested compounds with SC50 values of5.50 and 4.30 μg/ml, respectively, compared to ascorbic acid as standard and the total antioxidant capacity (TAC) values of 605.0 and 680.59 mg ascorbicacid equivalent/g compound, respectively. In vitro antimicrobial activities of the isolated compounds were tested using disc agar plate method againstfour pathogenic microbial strains including Gram-positive, Gram-negative bacteria and yeast with inhibition zones from 9 to 19 mm. Gas chromatographymassspectrometry analysis for the essential oil provides twenty four identified components representing 92% of its total oil composition.Conclusion: The results supported that S. jambos could be attributed to sources of natural antioxidant and antimicrobial applications

Dexmedetomidine as an adjuvant to bupivacaine in ultrasound fascia iliaca compartment block in proximal end femur surgeries

Background: Fracture neck femur is a common cause of hospital admission among the elderly population. Many patients admitted with fracture femur have long-standing cardiac, hepatic or renal problems. This makes a challenge to balance adequate analgesia with side effects of opioids. Fascia iliaca compartment block (FICB) is one of the peripheral nerve block techniques. It became widely used in providing postoperative analgesia for patient with fracture neck femur either in emergency department or in the operating room.Objective: To evaluate the efficacy of addition of dexmedetomidine to bupivacaine on the duration and quality of postoperative analgesia in ultrasound guided fascia iliaca compartment block in proximal end femur surgeries.Patients and methods: Sixty patients with American Society of Anesthesiologists (ASA) physical status I - II of both sexes aged from 20-60 years scheduled for proximal end femur surgeries. They were randomly assigned to one of two equal groups (n=30 each), using closed envelope technique: Bupivacaine group (B group), and Bupivacaine + dexmedetomidine (BD group). Result: Our study demonstrated prolongation of postoperative analgesia in bupivacaine-dexmedetomidine group (BD) compared to bupivacaine group (B). It showed statistically significant reduction in cumulative pethidine doses and prolongation in the time till first rescue analgesic is required in the BD group in comparison with the B group in the first 24 hours. Hemodynamic changes and incidence of side effects, were statistically insignificant among the two groups. Conclusion: Addition of dexmedetomidine, as an adjuvant to the local anesthetic bupivacaine, in ultrasound fascia iliaca compartment block provides prolongation of the duration of postoperative analgesia with less opioid consumption without remarkable side effects

EFFECT OF IRON OVERLOAD AND IRON CHELATORS ON ANTI-MÜLLERIAN HORMONE LEVEL IN EGYPTIAN FEMALE PATIENTS WITH TRANSFUSION DEPENDENT β-THALASSEMIA

Objective: This work aims to determine the effect of iron overload on serum anti-müllerian hormone (AMH) levels in females subjected to transfusion-dependent β-thalassemia by measuring serum ferritin and to investigate the effects of iron chelation therapy including oral deferiprone and subcutaneous deferoxamine in the management of transfusion-related iron overload together with reproductive function.Methods: 90 female patients with thalassemia major (TM), thalassemia intermedia (TI) and thalassemia minor (T minor) were selected to investigate AMH by ELISA and ferritin by IRMA.Results: Serum AMH level was lower in female patients with transfusion dependent β-thalassemia than in T minor also, Ferritin was 25 fold more in TM compared to T minor (3088.0±2497.6 ng/ml vs. 120.3±36.2 ng/ml). There was significant negative correlation of AMH with ferritin in TM (r =-0.949; P<0.001*), in TI (r =-0.378; P =0.039*) and in T minor (r =-0.754; P<0.001*). The iron chelator, deferoxamine had significantly higher ferritin and lower AMH in TM and TI than deferiprone.Conclusion: the results demonstrated that females with TM and TI were found to have lower serum AMH levels than T minor and inversely related to the serum ferritin levels in all thalassemic groups. Also, it demonstrated that deferiprone was more efficient than deferoxamine in removing excess iron and reduced the deleterious effect of excess iron to the reproductive system, which leads to fertility preservation of female patients with transfusion–dependent β-thalassemia.Keywords: Anti-müllerian hormone, Ferritin, Iron overload, β-thalassemia, Deferoxamine, Deferiprone

Synthesis of novel naphthalene-heterocycle hybrids with potent antitumor, anti-inflammatory and antituberculosis activities

Multitarget-directed drugs (hybrid drugs) constitute an efficient avenue for the treatment of multifactorial diseases. In this work, novel naphthalene hybrids with different heterocyclic scaffolds such as nicotinonitrile, pyran, pyranopyrazole, pyrazole, pyrazolopyridine, and azepine were efficiently synthesized via tandem reactions of 3-formyl-4H-benzo[h]chromen-4-one 1 with different nucleophilic reagents. Analysis of these hybrids using PASS online software indicated different predicted biological activities such as anticancer, antimicrobial, antiviral, antiprotozoal, anti-inflammatory, etc. By focusing on antitumor, anti-inflammatory, and antituberculosis activities, many compounds revealed remarkable activities. While 3c, 3e, and 3h were more potent than doxorubicin in the case of HepG-2 cell lines, 3a–e, 3i, 6, 8, 10, 11, and 12b were more potent in the case of MCF-7. Moreover, compounds 3c, 3h, 8, 10, 3d, and 12b manifested superior activity and COX-2 selectivity to the reference anti-inflammatory Celecoxib. Regarding antituberculosis activity, 3c, 3d, and 3i were found to be the most promising with MIC less than 1 mg mL–1. The molecular docking studies showed strong polar and hydrophobic interactions with the novel naphthalene-heterocycle hybrids that were compatible with experimental evaluations to a great extent

Anti-Obesity Evaluation of Averrhoa carambola L. Leaves and Assessment of Its Polyphenols as Potential α-Glucosidase Inhibitors

Averrhoa carambola L. is reported for its anti-obese and anti-diabetic activities. The present study aimed to investigate its aqueous methanol leaf extract (CLL) in vivo anti-obese activity along with the isolation and identification of bioactive compounds and their in vitro α-glucosidase inhibition assessment. CLL improved all obesity complications and exhibited significant activity in an obese rat model. Fourteen compounds, including four flavone glycosides (1–4) and ten dihydrochalcone glycosides (5–12), were isolated and identified using spectroscopic techniques. New compounds identified in planta included (1) apigenin 6-C-(2-deoxy-β-D-galactopyranoside)-7-O-β-D-quinovopyranoside, (8) phloretin 3′-C-(2-O-(E)-cinnamoyl-3-O-β-D-fucopyranosyl-4-O-acetyl)-β-D-fucopyranosyl-6′-O-β-D fucopyranosyl-(1/2)-α-L arabinofuranoside, (11a) phloretin3′-C-(2-O-(E)-p-coumaroyl-3-O-β-D-fucosyl-4-O-acetyl)-β-D-fucosyl-6′-O-(2-O-β-D-fucosyl)-α-L-arabinofuranoside, (11b) phloretin3′-C-(2-O-(Z)-p-coumaroyl-3-O-β-D-fucosyl-4-O-acetyl)-β-D-fucosyl-6′-O-(2-O-β-D-fucosyl)-α-L-arabinofuranoside. Carambolaside M (5), carambolaside Ia (6), carambolaside J (7), carambolaside I (9), carambolaside P (10a), carambolaside O (10b), and carambolaside Q (12), which are reported for the first time from A. carambola L. leaves, whereas luteolin 6-C-α-L-rhamnopyranosyl-(1-2)-β-D-fucopyranoside (2), apigenin 6-C-β-D-galactopyranoside (3), and apigenin 6-C-α-L-rhamnopyranosyl-(1-2)-β-L-fucopyranoside (4) are isolated for the first time from Family. Oxalidaceae. In vitro α-glucosidase inhibitory activity revealed the potential efficacy of flavone glycosides, viz., 1, 2, 3, and 4 as antidiabetic agents. In contrast, dihydrochalcone glycosides (5–11) showed weak activity, except for compound 12, which showed relatively strong activity