Design, Synthesis, Characterization, and Molluscicidal Activity Screening of New Nicotinonitrile Derivatives against Land Snails, M. cartusiana.

A new series of nicotinonitrile derivatives 2-7 was designed and synthesized from the starting material (E)-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (1) to assess their molluscicidal activity. The newly synthesized nicotinonitrile compounds 2-7 were characterized based on FTIR, 1H-NMR, and 13C-APT NMR spectra as well as elemental microanalyses. The target compounds 2-7 were screened for their toxicity effect against M. cartusiana land snails and were compared to Acetamiprid as a reference compound. The results demonstrated that the nicotinonitrile-2-thiolate salts 4a and 4b had good mortality compared with that of Acetamiprid. The results of the in vivo effect of the prepared nicotinonitrile molecules 2, 4a, and 4b on biochemical parameters, including AChE, ALT, AST, and TSP, indicated a reduction in the level of AChE and TSP as well as an increase in the concentration of transaminases (ALT and AST). A histopathological study of the digestive gland sections of the M. cartusiana land snails was carried out. The nicotinonitrile-2-thiolate salts 4a,b showed vacuolization, causing the digestive gland to lose its function. It could be concluded that the water-soluble nicotinonitrile-2-thiolate salts 4a,b could be adequate molluscicidal molecules against M. cartusiana land snails.

Chitosan-glucan complex hollow fibers reinforced collagen wound dressing embedded with aloe vera. II. Multifunctional properties to promote cutaneous wound healing.

This study presents an innovative multifunctional system in fabricating new functional wound dressing (FWD) products that could be used for skin regeneration, especially in cases of infected chronic wounds and ulcers. The innovation is based on the extraction, characterization, and application of collagen (CO)/chitosan-glucan complex hollow fibers (CSGC)/aloe vera (AV) as a novel FWS. For the first time, specific hollow fibers were extracted with controlled inner (500-900 nm)/outer (2-3 µm) diameters from mycelium of Schizophyllum commune. Further on, research and evaluation of morphology, hydrolytic stability, and swelling characteristics of CO/CSGC@AV were carried out. The obtained FWS showed high hydrolytic stability with enhanced swelling characteristics compared to native collagen. The hemostatic effect of FWS increased significantly in the presence of CSGC, compared to native CO and displayed excellent biocompatibility which was tested by using normal human dermal fibroblast (NHDF). The FWS showed high antibacterial activity against different types of bacteria (positive/negative grams). From in vivo measurements, the novel FWS increased the percentage of wound closure after one week of treatment. All these results imply that the new CO/CSGC@AV-FWD has the potential for clinical skin regeneration and applying for controlled drug release.

Analysis of some chlorophenoxy acids and carbamate herbicides in water and soil as amide derivatives using gas chromatography-mass spectrometry.

A newly developed method for determining three phenoxy acids and one carbamate herbicide in water and soil samples using gas chromatography with mass spectrometric detection is developed. Phenoxy acids are derivatized through a condensation reaction with a suitable aromatic amine. 1,1-Carbonyldiimidazole is used as a condensation reagent. Derivatization conditions are optimized with respect to the amount of analyte, amine, solvent, and derivatization reagent. The optimum derivatization yield is accomplished in acetonitrile. 4-Methoxy aniline is used as a derivatizing agent. Obtained derivatives are stable indefinitely. Enhancement in sensitivity is achieved by using the single-ion monitoring mass spectrometric mode. The effectiveness of the developed method is tested by determining investigated compounds in water and soil samples. Analytes are concentrated from water samples using liquid-phase extraction and solid-phase extraction. Soil samples are extracted using methanol. Detection limits of 1.00, 50.00, 100.00, and 1.00 ng/mL are obtained for 2-(1-methylethoxy)phenyl methylcarbamate (Baygon), 2-(3-chlorophenoxy)-propionic acid (Cloprop), 2,4,5-trichlorophenoxyacetic acid, and 4-(2,4-dichlorophenoxy)butyric acid, respectively. LPE for spiked water samples yields recoveries in the range of 60.6-95.7%, with relative standard deviation (RSD) values of 1.07-7.85% using single component calibration curves. Recoveries of 44.8-275.5%, with RSD values ranging from 1.43% to 8.61% were obtained using a mixed component calibration curves. SPE from water samples and soil samples showed low recoveries. The reason is attributed to the weak sorption capabilities of soil and Al(2)O(3).

Intraoperative evaluation of axillary sentinel lymph nodes using touch imprint cytology and immunohistochemistry. Part II. Results.

AIM: In order to operate selectively on positive axillae during the initial operative session for early breast cancer, an accurate and rapid intraoperative method to examine an axillary node sample (ANS) or a sentinel node biopsy (SNB) is required. The aim of this study was to determine the feasibility and accuracy of Immunohistochemistry (IHC)-stained touch imprints in detecting metastatic axillary nodes intraoperatively. MATERIAL AND METHODS: Four hundred and thirty-two axillary nodes from 52 patients (23 axillary node clearance (ANC), 15 ANS and 14 SNB) were bisected, imprinted and stained with anti-cytokeratin 19 IHC. Results were compared with those of routine haematoxylin and eosin (H&E)-stained sections. RESULTS: IHC imprints detected 32 positive nodes from 12 patients. H&E sections detected 31 positive nodes from 11 patients. IHC imprints missed metastases in three nodes and missed the diagnosis of positive axillae in two patients. H&E missed metastases in four nodes and missed the diagnosis of positive axillae in 3 patients. On a node-basis, sensitivities were 91.4 and 88.5%, negative predictive values (NPV) were 99.2 and 99.0% and overall accuracies were 99.3 and 99.1% for IHC imprints and H&E sections, respectively. On a patient-basis, sensitivities were 85.7 and 78.5%, NPVs were 95.2 and 93.1% and overall accuracies were 96.1 and 94.2% for IHC imprints and H&E sections respectively. There were no false positives. Interpretation of the results by a non-histopathologist was concordant with that of a histopathologist. Results might be obtained within 30-45 min depending on the number of examined nodes. CONCLUSION: Intraoperative IHC staining of touch imprints of axillary sentinel nodes is feasible and is a reliable method for evaluating axillary nodes. Slides can be reliably interpreted by a trained non-histopathologist.

Fluorimetric determinations of nucleic acids using iron, osmium and samarium complexes of 4,7-diphenyl-1,10-phenanthroline.

New sensitive, reliable and reproducible fluorimetric methods for determining microgram amounts of nucleic acids based on their reactions with Fe(II), Os(III) or Sm(III) complexes of 4,7-diphenyl-1,10-phenanthroline are proposed. Two complementary single stranded synthetic DNA sequences based on calf thymus as well as their hybridized double stranded were used. Nucleic acids were found to react instantaneously at room temperature in Tris-Cl buffer pH 7, with the investigated complexes resulting in decreasing their fluorescence emission. Two fluorescence peaks around 388 and 567 nm were obtained for the three complexes using excitation lambda(max) of 280 nm and were used for this investigation. Linear calibration graphs in the range 1-6 microg/ml were obtained. Detection limits of 0.35-0.98 microg/ml were obtained. Using the calibration graphs for the synthetic dsDNA, relative standard deviations of 2.0-5.0% were obtained for analyzing DNA in the extraction products from calf thymus and human blood. Corresponding Recovery% of 80-114 were obtained. Student's t-values at 95% confidence level showed insignificant difference between the real and measured values. Results obtained by these methods were compared with the ethidium bromide method using the F-test and satisfactory results were obtained. The association constants and number of binding sites of synthetic ssDNA and dsDNA with the three complexes were estimated using Rosenthanl graphic method. The interaction mechanism was discussed and an intercalation mechanism was suggested for the binding reaction between nucleic acids and the three complexes.

Application of nuclear magnetic resonance spectroscopy for quantitative analysis of miconazole, metronidazole and sulfamethoxazole in pharmaceutical and urine samples.

Specific, accurate and precise NMR methods were developed for determining miconazole, metronidazole and sulfamethoxazole antibiotic drugs in authentic, pharmaceutical and urine samples. Proton nuclear magnetic resonance spectroscopy (1H NMR) with maleic acid as an internal standard and DMSO-d6 as NMR solvent were used. 1H NMR signals at 9.0, 8.06, 7.50 and 6.26 ppm corresponding to miconazole, metronidazole, sulfamethoxazole and maleic acid were respectively used for calculating the concentrations of drugs per unit dose. Average percent recoveries of (97.54-101.10), (98.06-100.46) and (97.83-102.83) with average uncertainties of 1.02, 0.45 and 0.86 were respectively obtained for determining authentic samples of miconazole, metronidazole and sulfamethoxazole in the concentration range of 0.92-170 mg/0.6 ml DMSO-d6. In pharmaceutical formulations and urine samples, average percent recoveries in the ranges of 97.50-101.33 and 94.46-100.86 were respectively obtained. Relative standard deviations (R.S.D.)

Quantitative determinations of levofloxacin and rifampicin in pharmaceutical and urine samples using nuclear magnetic resonance spectroscopy.

Rapid, specific and simple methods for determining levofloxacin and rifampicin antibiotic drugs in pharmaceutical and human urine samples were developed. The methods are based on (1)H NMR spectroscopy using maleic acid as an internal standard and DMSO-d6 as NMR solvent. Integration of NMR signals at 8.9 and 8.2 ppm were, respectively, used for calculating the concentration of levofloxacin and rifampicin drugs per unit dose. Maleic acid signal at 6.2 ppm was used as the reference signal. Recoveries of (97.0-99.4)+/-0.5 and (98.3-99.7)+/-1.08% were obtained for pure levofloxacin and rifampicin, respectively. Corresponding recoveries of 98.5-100.3 and 96.8-100.0 were, respectively, obtained in pharmaceutical capsules and urine samples. Relative standard deviations (R.S.D.) values < or =2.7 were obtained for analyzed drugs in pure, pharmaceutical and urine samples. Statistical Student's t-test gave t-values < or =2.87 indicating insignificant difference between the real and the experimental values at the 95% confidence level. F-test revealed insignificant difference in precisions between the developed NMR methods and each of fluorimetric and HPLC methods for analyzing levofloxacin and rifampicin.

Spectrophotometric and fluorimetric determination of diazepam, bromazepam and clonazepam in pharmaceutical and urine samples.

New spectrophotometric and fluorimetric methods have been developed to determine diazepam, bromazepam and clonazepam (1,4-benzodiazepines) in pure forms, pharmaceutical preparations and biological fluid. The new methods are based on measuring absorption or emission spectra in methanolic potassium hydroxide solution. Fluorimetric methods have proved selective with low detection limits, whereas photometric methods showed relatively high detection limits. Successive applications of developed methods for drugs determination in pharmaceutical preparations and urine samples were performed. Photometric methods gave linear calibration graphs in the ranges of 2.85-28.5, 0.316-3.16, and 0.316-3.16 microgml-1 with detection limits of 1.27, 0.08 and 0.13 microgml-1 for diazepam, bromazepam and clonazepam, respectively. Corresponding average errors of 2.60, 5.26 and 3.93 and relative standard deviations (R.S.D.s) of 2.79, 2.12 and 2.83, respectively, were obtained. Fluorimetric methods gave linear calibration graphs in the ranges of 0.03-0.34, 0.03-0.32 and 0.03-0.38 microgml-1 with detection limits of 7.13, 5.67 and 16.47 ngml-1 for diazepam, bromazepam and clonazepam, respectively. Corresponding average errors of 0.29, 4.33 and 5.42 and R.S.D.s of 1.27, 1.96 and 1.14 were obtained, respectively. Statistical Students t-test and F-test have been used and satisfactory results were obtained.

Intraoperative evaluation of axillary sentinel lymph nodes using touch imprint cytology and immunohistochemistry: I. Protocol of rapid immunostaining of touch imprints.

AIMS: Sentinel Node Biopsy (SNB) is considered an accurate method of detecting axillary lymph node status in patients with small breast cancer. Combined with an accurate and rapid histopathology tool, it could spare this group of patients unnecessary Axillary Node Clearance (ANC) with its associated hazards. Intraoperative examination of SNB for cancer cells has been investigated using both Frozen Sections (FS) and Imprint Cytology (IC) stained with different stains. This study is devoted to establish a reliable and rapid protocol for immunostaining of touch imprints from SNB. METHODS: We investigated two different EPOS (Enhanced Polymer One-Step staining--DAKO) anticytokeratin antibodies, five different tissue fixatives and different incubation periods and temperatures with both positive and negative controls. RESULTS: We have developed a protocol, which produced good and consistent immunostaining of touch imprints. The initial results using this protocol are concordant with those of permanent Haematoxylin and Eosin (H&E) sections. CONCLUSIONS: We propose this protocol for rapid immunostaining of touch imprints of SNB.

Evaluation of axillary lymph nodes using touch imprint cytology and immunohistochemistry.

BACKGROUND: The success of sentinel node biopsy in determining axillary lymph node status necessitates an accurate and rapid method for intraoperative examination of the nodes. The aim was to determine the feasibility and accuracy of immunohistochemistry (IHC) of touch imprints in detecting axillary nodal metastases intraoperatively. METHODS: Some 344 axillary nodes from 30 patients with early breast cancer were bisected, imprinted and subjected to IHC. Results were compared with those of routine haematoxylin and eosin examination of the same nodes. RESULTS: Using IHC, 29 nodes from nine patients were positive for metastases. Using haematoxylin and eosin, 28 nodes from eight patients were positive. On a patient basis, the sensitivities of IHC and haematoxylin and eosin were 100 and 88.9 per cent, and negative predictive values (NPVs) were 100 and 95.5 per cent, respectively. On a node basis, the sensitivities were 96.7 and 93.3 per cent, and NPVs were 99.7 and 99.3 per cent, respectively. There were no false positives. The results were obtained within 30-45 min, depending on the number of nodes examined. CONCLUSION: IHC of touch imprints can provide a fast and sensitive method for detecting metastases in axillary nodes during breast cancer surgery.

Fracture of the penis: surgical management.

Fracture of the penis is a rare injury, only 135 patients having been reported by 1985. Our recent experience with six patients who underwent emergency surgery, has been documented. The results of treatment were excellent with complete recovery of function. The study recommends operative management as the treatment of choice.

Experimental studies on brucellosis in chickens.

The present study was carried out on 30 one-day old and 50 six-months old chicks in two separate experiments. Exposure of one-day old chickens to Br. abortus showed no apparent clinical signs, although the microorganism was recovered from 2 out of 10 infected cases. 40% of chicks which were exposed to Br. melitensis showed signs of illness 48-72 hours post infection with fatal termination within 12-36 hours after onset of symptoms. The microorganism was isolated from 6 out of 10 infected chicks. Adult chicks, when exposed to Brucella infection showed no clinical signs except a slight decrease in egg-yield among hens infected intraperitoneally with Br. melitensis, although brucella organisms were recovered from droppings, egg-shell, egg-yolk and white, and from internal organs of some chicks. Bacteriological evaluation of diagnostic procedures showed that Rose Bengal and Brucellosis card tests were efficient for the diagnosis of brucellosis in chickens. The brucellin test proved its efficacy when applied in the wattle, better than in wing-folds with a peak of reaction within 48 to 72 hours post inoculation. Brucella organisms isolated from experimentally infected chicks were identical to the original strains used. In droppings of chicks Br. melitensis survived for 48 days at room temperature (12-22 degrees C). Beside the economical losses resulting from infection by Br. melitensis of one-day old chicks, the results obtained assure the significance of infected chicks, their eggs and droppings in disseminating brucellosis for man and animals.

Synthesis and biological activity of some new 3,6-dinitro-1:8-naphthaloyl- and 3,6-diamino-1:8-naphthaloylamino acids and dipeptide derivatives.

Synthesis of a series of 3,6-dinitro-1:8-naphthaloylamino acids (II-IX) and some of their corresponding methyl esters (X-XVI) and 3,6-diamino-1:8-naphthaloylamino acid derivatives (XXIX-XXXVI) is described. Coupling of 3,6-dinitro-1:8-naphthaloylamino acids with amino acid methyl ester hydrochlorides in dioxane-DMF-Et3N medium using DCC method furnishes the desired 3,6-dinitro-1:8-naphthaloyldipeptide methyl esters (XVII-XXVIII). Most of the synthesized 3,6-dinitro-1:8-naphthaloylamino acids, esters and dipeptide derivatives (compounds III-VI, XI-XV, XVII, XIX-XXI, XXIII and XXV) and 3,6-diamino-1:8-naphthaloylamino acid derivatives (XXIX-XXXV) were found to be active against a number of microorganisms.

Ruminal and salivary concentration of some sulphonamides in cows and their effect on rumen flora.

Sulphadiazine, sulphatiazole and sulphamerazine were shown to be excreted through the ruminal wall and salivary glands of cows. These sulphonamides had a slight inhibitory effect on cellulose digestion and on the activity of rumen infusoria. Acetylation of the sulphonamides occurred to a slight extent. Sulphatiazole was more acetylated (16.2 per cent) than sulphadiazine (7.0 per cent) or sulphamerazine (8.4 per cent). The rate of elimination of the three compounds, as indicated by their half lives, showed that sulphathiazole was the most rapidly excreted (2 h), whereas sulphadiazine and sulphamerazine were more slowly excreted, 5.4 and 7.1 h respectively.

"Mediterranean abdominal lymphoma" or immunoproliferative small intestinal disease. Part II: pathological aspects.

The pathology of 25 cases of Mediterranean abdominal lymphoma, better designated as immunoproliferative small intestinal disease (IPSID), are reported from the American University of Beirut Hospital. The series includes nine cases with documented alpha heavy chain disease (alpha-HCD). The disease is characterized by the presence of a diffuse and compact bandlike lymphoplasmacytic infiltration of the proximal small intestinal mucosa. The presence of a concomitant malignant lymphoma in the intestine and/or mesenteric lymph nodes, and of alpha-heavy protein in the serum is commonly encountered. Two histopathologic variants of IPSID are present. The first is characterized by the diffuse infiltration of the mucosa, at sites away from tumoral masses, by either pure plasmacytic infiltration, or mixed lymphoplasmacytic infiltration. This variety is associated with the immunoblastic sarcoma type of malignant lymphoma, and with alpha chain disease (alpha-HCD). The second variant is characterized by a diffuse follicular lymphoid hyperplasia pattern in the small intestinal mucosa. The associated malignant lymphoma is diffuse and undifferentiated often having a starry-sky pattern. This variety is not associated with alpha-HCD. Both histologic variants share the same clinical antecedents. In five patients, mesenteric lymph nodes harbored immunoblastic sarcoma while the intestinal mucosae of the same patients were involved with a benign appearing lymphoplasmacytic infiltration. This finding stresses the need for staging laparatomy. Three patients, with alpha-HCD, had peripheral lymph node involvement with immunoblastic sarcoma. The disease apparently evolves in two stages: an immunoproliferative phase, probably reversible, and a later development of malignant lymphoma. The term immunoproliferative small intestinal disease accurately describes the nature of the entity.

Primary intestinal lymphoma with paraproteinemia.

Five cases of primary intestinal lymphoma are described. The main clinical features included abdominal pain, diarrhea, and marked weight loss, together with radiologic and some laboratory findings suggestive of malabsorption. Laparatomy perfomed in four cases revealed dilatation of the small intestine, with mesenteric node enlargement. In these four instances there was a definite histologic evidence of malignant lymphoma, either initially or later in the course of the disease. A characteristic feature here was the diffuse infiltration of the intestinal mucosa with plasma cells, which in the deeper layers became progressively atypical and were mixed with histiocytes and giant cells. A similar infiltrate was seen in the mesenteric nodes. Immunoelectrophoresis showed the pattern of IgA heavy chain disease. It is suggested that the latter is a variant of primary intestinal lymphoma and not a separate disease entity.