One-pot three-component synthesis of peptidomimics for investigation of antibacterial and antineoplastic properties

AbstractThe α-hydroxyphosphonate generated from dialkyl phosphites and 1-phenyl-1H-pyrazole-4-carbaldehyde derivative was, in situ, trapped by isothiocyanates, isocyanates or acetic anhydride to produce dialkyl phosphorylmethyl-carbamothioates, -carbamates and/or -methyl acetates in good yields. The reactions were carried out in tetrahydrofuran (THF) in one step at room temperature, using K2CO3 catalyst. Antimicrobial and antineoplastic activities of the synthesized compounds were estimated. The results showed that all new compounds cause moderate to good antibiotic activities. However, phosphorylmethylcarbamothioates exhibited the highest growth inhibition. Furthermore, selected nine new synthesized compounds were evaluated for anticancer activity against eight human tumor cell lines (MCF7, MDA-MB-435, BT-549, IGROVI, SK-OV-3, PX-3, PU-145, and HEPG2). The majority of these compounds revealed moderate to potent activity against MCF7, PU-145, and HEPG2. Among them, two of the phosphorylmethylcarbamothioates showed excellent broad spectrum of anticancer activity with IC50 values ranging from 16.6 to 26.9 and 17.2 to 36.9μmolL−1, respectively (for 5-fluorouracil IC50: 17.7 to 38.8μmolL−1). Phosphorylmethyl methylcarbamothioate, in particular was more potent than 5-fluorouracil against all tested human carcinoma cell lines

Antigen-Presenting Cell/Tumour Cell Hybrid Vaccines in Cancer Immunotherapy

In recent years, there has been a considerable interest in the development of immunotherapeutic approaches for treating cancers, including strategies for inducing antigen-specific cytotoxic T cells (CTLs) capable of killing tumour cells in situ. These approaches include both the active induction of CTLs by vaccination of tumour bearing patients, and the ex vivo expansion of tumour-specific CTLs for adoptive cellular transfer. One promising approach has been through the generation of hybrid cells, formed by fusion of professional antigen presenting cells (pAPCs) with tumour cells expressing relevant tumour associated antigens. Dendritic cells (DCs) represent the most potent form of pAPCs, and have been widely used in the generation of APC/tumour cell hybrid vaccines, in the context of a range of tumour types. Studies of fusion cell vaccines in animals have demonstrated not only the induction of tumour-specific CTLs, but also protection against subsequent tumour challenge and regression of established tumours. Results of clinical trials in patients have been less dramatic, but have shown the ability of hybrid vaccines to induce tumour-specific T cell responses, in some instances associated with disease stabilization or tumour regression. In addition to dendritic cell fusion vaccines, a number of non-DC fusion vaccines have been described

Intralesional Injection of Botulinum Toxin for Post-Herpetic Neuralgia: A Pilot Study

Background: When someone has herpes zoster and the rash goes away in spite of persistence of pain, they are defined to have post-herpetic neuralgia (PHN). Herpes zoster is frequently accompanied by post-herpetic neuralgia. Clostridium botulinum produces botulinum toxin (BTX-A), a neurotoxic protein that is used to treat various ailments. Objective: Intralesional botulinum toxin injections were tested for their efficacy in the treatment of post herpetic neuralgia. Patients and methods: An intralesional BTX-A injections pilot trial including 19 patients with PHN was carried out. Quality of life scale (QLS), neuropathy pains scale (NPS), and pain analyses by visual analogue scale (VAS) were used for all patients after comprehensive history-taking process.Results: After a six-months therapy follow-up period, we found significant differences comparing before and after treatment in the neuropathy pain scale, VAS score, and the QLS (SF-36). Pain at site of injection was found in all patients while redness or erythema was found in 13 patients. Conclusion: Treatment with botulinum toxin via local injection is beneficial for post-herpetic neuralgia (PHN). BTX could be alternative therapeutic modality in treating PHN in the future

Urine carcinoembryonic antigen levels are more useful than serum levels for early detection of Bilharzial and non-Bilharzial urinary bladder carcinoma: Observations of 43 Egyptian cases

BACKGROUND: Both urinary bilharziasis and urothelial neoplasia are associated with increased production of tissue carcinoembryonic antigen (CEA). PATIENTS AND METHODS: Urine and serum CEA were determined in 43 patients with urinary bladder carcinoma including 22 post bilharzial and 21 nonbiharzial cases, in addition to 10 normal control cases. RESULTS: A significant increase was detected in both urine and serum CEA levels with bladder carcinoma compared to control cases. Urinary CEA was significantly elevated in 86% of bilharzial, versus 62% in nonbilharzial bladder carcinoma. Only 10.5% of control cases had urinary CEA elevation. The mean urinary CEA in bilharzial, was higher than that of nonbilharzial carcinoma, but the difference was not statistically significant. There was a definite relationship between urine CEA and the stage of malignancy; the higher the stage, the higher the level of urine CEA. No relationship could be detected between the stage of malignancy and serum CEA, or between the grades of malignancy and urine or serum CEA levels. CONCLUSION: Urinary CEA is more useful than serum CEA in the early detection of urotherlial carcinoma particularly if provoked by bilharziasis. Its level is also correlated with the tumor stage

Photo-identification of Dugongs in Marsa Alam and Wadi El Gemal National Park, Egypt

1351-1358Using photo-identification techniques, 30 dugongs were recorded at the southern Egyptian Red Sea coast between December 2015 and October 2017, 16 at Marsa Alam and 14 at Wadi El Gemal National Park (WGNP). Males were recorded seven times more frequently than females and calves were also recorded. A Photo ID catalogue was prepared for the dugongs with records of their occurrence among sites. We confirmed the presence of particular dugong specific sites. Long- and short-distance movements within the study sites were recorded for eight different dugongs. This is the first study to document the number of dugongs in inshore areas of the Egyptian Red Sea coast. Further studies are recommended for offshore sites in WGNP for better documentation of this group of animals

INVESTIGATION OF SOME CHEMICAL CONSTITUENTS AND ANTIOXIDANT ACTIVITY OF ASPARAGUS SPERNGERI

Objective: Asparagus sprengeri (A S) is an ornamental plant cultivated in EGYPT. This study was designed to investigate some lipid and flavanoid constituents, in addition to the evaluation of antioxidant activity of different extracts of the plant. Methods: Two phospholipid were identified by (HPTLC). The fatty acid methyl ester and unsaponifiable matter were analyzed by GC. Four flavonoids were isolated by CC and purified by PPc. Identification of isolated flavanoidal compounds was carried by spectroscopic analysis Viz, TLC,PC, UV, EL-MS and H-1– NMR. The different extracts were tested for their free radical scavenging activity using DPPH and β-Carotene- linoleic acid bleaching assay. Results: Four flavonoids, were isolated, apigenin, dihydroquercitin, naringenin, apigenin- 7-o- glucoside Nine fatty acids, Myrestic and linoliec acids were the major components. The unsaponifiable matter was found to be a mixture of hydrocarbons from (C13– C28) and cholesterol two classes of phospholipid were identified namely L-α-Phosphatidyl-DL-glycerol and L-α- Phosphatidylethanolamine. The alcoholic extract of the plant has moderate antioxidant activity with EC50 0.114 and 0.110 mg/ml for the DppH and β-carotene methods respectively Conclusion: Asparagus sprengeri can be used as the natural antioxidant. Flavonoids are suggested to be a group of key antioxidants in Asparagus

Photo-identification of Dugongs in Marsa Alam and Wadi El Gemal National Park, Egypt

1351-1358Using photo-identification techniques, 30 dugongs were recorded at the southern Egyptian Red Sea coast between December 2015 and October 2017, 16 at Marsa Alam and 14 at Wadi El Gemal National Park (WGNP). Males were recorded seven times more frequently than females and calves were also recorded. A Photo ID catalogue was prepared for the dugongs with records of their occurrence among sites. We confirmed the presence of particular dugong specific sites. Long- and short-distance movements within the study sites were recorded for eight different dugongs. This is the first study to document the number of dugongs in inshore areas of the Egyptian Red Sea coast. Further studies are recommended for offshore sites in WGNP for better documentation of this group of animals

Assessment the impact of 17α-methyltestosterone hormone on growth, hormone concentration, molecular and histopathological changes in muscles and testis of Nile tilapia; Oreochromis niloticus

Abstract: The present study was designed to explain clearly why methyltestosterone is widely used by the Egyptian producers of farmed tilapia and also to investigate its fate in treated fish to guarantee that no hazards on consumers, producers and on the environment. In this study, samples of untreated and treated Nile tilapia were collected at several time intervals. Water quality parameters were within the acceptable range for fish growth. The present analyses showed highly significant increase in body weight, body length, condition factor (K), HSI and GSI, between different time intervals (April -November, 2009) in the untreated control and treated groups. On the other hand, plasma testosterone and residual concentration of testosterone hormone in muscle showed highly significant differences between the studied months in untreated control and treated groups. Molecular biological analyses revealed that methyltestosterone was able to induce DNA fragmentation and molecular genetic variability (using RAPD-PCR fingerprinting pattern) in the testis tissues of the treated Nile tilapia; Oreochromis niloticus, which was higher in the first four studied months than the untreated control tilapia. Additionally, histopathological examination showed no changes and no traces of hormone accumulation in the muscle structure. Testis showed moderate number of spermatozoa followed by increasing in number of spermatozoa at the end of the study

Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals

BACKGROUND: Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer drug used in the treatment of variety of cancers .Its use is limited by its cardiotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of DOX and at the same time its protective effect against DOX-induced cardiotoxicity in rats. METHODS: Ehrlich ascites carcinoma bearing mice were used in this study. Percent survival of tumor bearing mice was used for determination of the Cytotoxic activity of DOX in presence and absence of RSVL. Uptake and cell cycle effect of DOX in tumor cells in the presence of RSVL was also determined. Histopatholgical examination of heart tissues after DOX and/or RSVL therapy was also investigated. RESULTS: DOX at a dose level of 15 mg/kg increased the mean survival time of tumor bearing mice to 21 days compared with 15 days for non tumor-bearing control mice. Administration of RSVL at a dose level of 10 mg/kg simultaneously with DOX increased the mean survival time to 30 days with 70% survival of the tumor-bearing animals. RSVL increased the intracellular level of DOX and there was a strong correlation between the high cellular level of DOX and its cytotoxic activity. Moreover, RSVL treatment showed 4.8 fold inhibition in proliferation index of cells treated with DOX. Histopathological analysis of rat heart tissue after a single dose of DOX (20 mg/kg) showed myocytolysis with congestion of blood vessels, cytoplasmic vacuolization and fragmentation. Concomitant treatment with RSVL, fragmentation of the muscle fiber revealed normal muscle fiber. CONCLUSION: This study suggests that RSVL could increase the cytotoxic activity of DOX and at the same time protect against its cardiotoxicity

Diagnostic efficacy of monoclonal antibody based sandwich enzyme linked immunosorbent assay (ELISA) for detection of Fasciola gigantica excretory/secretory antigens in both serum and stool

<p>Abstract</p> <p>Background</p> <p>This research was carried out to develop a reliable monoclonal antibody (MoAb)-based sandwich enzyme linked immunosorbent assay (ELISA) for the diagnosis of active <it>Fasciola gigantica </it>infection in both serum and stool for comparative purposes.</p> <p>Methods</p> <p>From a panel of MoAbs raised against <it>F. gigantica </it>excretory/secretory antigens (ES Ags), a pair (12B/11D/3F and 10A/9D/10G) was chosen due to its high reactivity and strict specificity to <it>F. gigantica </it>antigen by indirect ELISA.</p> <p>Results</p> <p>The two MoAbs were of the IgG₁and IgG_2asubclasses, respectively. Using SDS-PAGE and EITB, the selected MoAbs recognized 83, 64, 45 and 26 kDa bands of ES Ags. The lower detection limit of ELISA assay was 3 ng/ml. In stool, the sensitivity, specificity and diagnostic efficacy of ELISA was 96%, 98.2 and 97.1%; while in serum they were 94%, 94.6% and 94.3%, respectively. Moreover, a positive correlation was found between ova count in stool of <it>F. gigantica </it>infected patients and the OD readings of ELISA in both stool and serum samples (<it>r </it>= 0.730, p < 0.01 and r = 0.608; p < 0.01, respectively).</p> <p>Conclusions</p> <p>These data showed that the use of MoAb-based sandwich ELISA for the detection of <it>F. gigantica </it>coproantigens in stool specimens was superior to serum samples; it provides a highly efficient, non-invasive technique for the diagnosis of active <it>F. gigantica </it>infection.</p