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1.
Int J Biol Macromol ; 66: 125-34, 2014 May.
Article in English | MEDLINE | ID: mdl-24530331

ABSTRACT

In this work, native cellulose cotton fibers were first modified through graft copolymerization of polyacrylonitrile (PAN) and then by insertion of phenyl thiosemicarbazide moieties to finally produce C-PTS chelating fibers, which were fully characterized using various instrumental techniques such as SEM, FTIR, EDX and XRD spectra. The obtained C-PTS were employed in removal and extraction of Au(3+), Pd(2+) and Ag(+) precious metal ions from their aqueous solutions using batch experiments. The kinetic studies showed that the pseudo-second-order model exhibited the best fit for the experimental data. In addition, the adsorption isotherm studies indicated that the adsorption follows the Langmuir model and the maximum adsorption capacities for Au(3+), Pd(2+) and Ag(+) were 198.31, 87.43 and 71.14 mg/g respectively.


Subject(s)
Cellulose/chemistry , Ions/chemistry , Metals/chemistry , Acrylic Resins/chemistry , Adsorption , Chelating Agents/chemistry , Cotton Fiber/methods , Hydrogen-Ion Concentration , Kinetics , Polymerization , Semicarbazides/chemistry , Solutions/chemistry , Temperature , Water Pollutants, Chemical/chemistry , Water Purification/methods
2.
Cell Prolif ; 46(5): 538-53, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24033536

ABSTRACT

OBJECTIVES: Dysregulation of Met signalling is associated with malignant transformation. Combined treatment has been shown to reduce Met activation and mammary tumour cell proliferation. Experiments here, were conducted to determine mechanisms involved in mediating anti-cancer effects of combined γ-tocotrienol and SU11274 (Met inhibitor) treatment in various mammary cancer cell lines. MATERIALS AND METHODS: Treatment effects on mouse (+SA) and human (MCF-7, and MDA-MB-231) mammary cancer cell lines, and normal mouse (CL-S1) and human (MCF10A) mammary epithelial cell lines were compared. Cell proliferation and survival were determined by MTT assay and Ki-67 staining; protein expression was determined by western blot analysis. Immunofluorescence staining was also used to characterize expression and localization of multiple epithelial and mesenchymal markers. Cell migration was determined using a wound-healing assay. RESULTS: Combined treatment with γ-tocotrienol and SU11274 resulted in synergistic inhibition of +SA, MCF-7, and MDA-MB-231, but not CL-S1 or MCF10A cell growth that was associated with reduction in Akt STAT1/5 and NFκB activation and corresponding blockade in epithelial-to-mesenchymal transition, as indicated by increased expression of E-cadherin, ß-catenin, and cytokeratins 8/18 (epithelial markers) and corresponding reduction in vimentin (mesenchymal marker) and reduction in cancer cell motility. CONCLUSIONS: Suggest that combined γ-tocotrienol and Met inhibitor treatment may provide benefit in treatment of breast cancers characterized by aberrant Met activity.


Subject(s)
Chromans/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Indoles/pharmacology , Piperazines/pharmacology , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Sulfonamides/pharmacology , Vitamin E/analogs & derivatives , Animals , Cadherins/metabolism , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Female , Humans , Keratin-18/metabolism , Keratin-8/metabolism , Ki-67 Antigen/chemistry , Ki-67 Antigen/metabolism , MCF-7 Cells , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-met/metabolism , STAT1 Transcription Factor/metabolism , STAT5 Transcription Factor/metabolism , Vimentin/metabolism , Vitamin E/pharmacology , beta Catenin/metabolism
3.
Eur J Gynaecol Oncol ; 31(3): 333-5, 2010.
Article in English | MEDLINE | ID: mdl-21077482

ABSTRACT

PURPOSE OF INVESTIGATION: Recurrent metastatic adenocarcinoma of the cervix is associated with an extremely poor prognosis. Treatment options for recurrent disease are limited and cure is extremely rare. CASE REPORT: We report a case of a 43-year-old patient with Stage IB adenocarcinoma of the cervix. She had multiple metastatic recurrence episodes salvaged with several radical surgeries, external and intraoperative irradiation, and chemotherapy over a survival period of 16 years. CONCLUSION: We conclude that long-term multi-modal salvage treatment may achieve longer survival in rare cases with recurrent metastatic adenocarcinoma of the cervix.


Subject(s)
Adenocarcinoma/therapy , Neoplasm Recurrence, Local/therapy , Uterine Cervical Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Combined Modality Therapy , Female , Humans , Neoplasm Recurrence, Local/mortality , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology
4.
J Egypt Soc Parasitol ; 40(2): 515-30, 2010 Aug.
Article in English | MEDLINE | ID: mdl-21246958

ABSTRACT

The study aimed to clarify whether vascular endothelial growth factor mRNA (VEGF mRNA) and TNFa mRNA in the HCC tissues on top of HCV with and without cirrhosis obtained from specimens after curative hepatic resection has a prognostic value and recurrence predictive value compared to other tumor criteria. A total of 160 patients were studied. The preoperative laboratory, radiological and staging to patients was done. Using in situ hybridization technique, VEGF mRNA and TNFa mRNA were determined in liver tissues of, 10 controls, 50 with HCC, 50 with HCV without cirrhosis and 50 HCV with cirrhosis. The results showed that in HCC cases there was positive correlation between increasing age, loss of weight, INR and AFP but not in other cases of CHC with or without cirrhosis. AFP, vascular invasion, encapsulation, tumor size and grade and platelet count were related to patients outcome and recurrence of tumor after follow up of most cases for 3 years. The expression of VEGF in liver tissues was proportional to progress of viral hepatitis to cirrhosis with more expression in cases progressed to malignant changes. More expression of VEGF in HCC was more evident with intense expression in cases with Vascular and capsular invasion and higher level of AFP. Expression of TNF alpha mRNA and VEGF mRNA shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positive with cases developed HCC.


Subject(s)
Gene Expression Regulation/immunology , Hepacivirus/genetics , Hepatitis C, Chronic/virology , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adult , Aged , Carcinoma, Hepatocellular/virology , Case-Control Studies , Female , Genotype , Hepatitis C Antibodies/blood , Hepatitis C, Chronic/metabolism , Humans , Liver Cirrhosis/virology , Liver Neoplasms/virology , Male , Middle Aged , RNA, Messenger/genetics , Tumor Necrosis Factor-alpha/genetics , Vascular Endothelial Growth Factor A/genetics
5.
Transplant Proc ; 36(4): 1194-8, 2004 May.
Article in English | MEDLINE | ID: mdl-15194414

ABSTRACT

The clinical application of islet transplantation is limited due to the limited source and the morbidity of systemic immunosuppression to prevent rejection. The two problems can be solved by using encapsulated islets. We have used amniotic membranes as biocompatible natural immune barriers. The objective of this study was to assess the revascularization of the membrane, which is necessary to ensure islet viability when the membrane is used for islet encapsulation. The amniotic membranes, obtained from full-term pregnant female dogs, were molded to form macrocapsules, which were implanted in the peritoneal cavity. The capsules were removed after 3, 10, 15, and 30 days and examined histopathologically using hematoxylin and eosin and by immunohistochemistry for neovascularization using factor VIII to detect angiogenesis. Upon histopathological examination, all specimens showed localized, moderate inflammation and congested blood vessels with no thrombosis or rejection. There was a mild degree of fibroblast proliferation starting from day 10 to day 30. Immunohistochemical staining revealed that the number of blood vessels was 7, 11, 13, 10 per high-power microscopic field on days 3, 10, 15, and 30, respectively. We concluded from this study that implanted amniotic sac capsules were vascularized within the omental tissue from day 10 on with significant blood vessel formation starting on day 3 by immunohistochemical study.


Subject(s)
Amnion/blood supply , Amnion/immunology , Islets of Langerhans/cytology , Neovascularization, Physiologic/physiology , Amnion/cytology , Animals , Capsules , Cell Culture Techniques , Cell Survival , Dogs , Female , Islets of Langerhans Transplantation/methods , Kinetics , Pregnancy , Transplantation, Heterologous
6.
Anal Sci ; 18(11): 1235-40, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12458709

ABSTRACT

A simple, selective and sensitive procedure is described for the preconcentration by flotation followed by spectrophotometric determination of trace amounts of Cd(II). Cadmium forms an intense red 1:2 complex with phenanthraquinone monophenylthiosemicarbazone (PPT) at pH > or = 6. The colored Cd-PPT complex was floated quantitatively with oleic acid (HOL) surfactant at pH 6.5, exhibiting maximum absorbance at 520 nm and having a molar absorptivity of 2.4 x 10(5) L mol(-1) cm(-1). The stability constant of the formed complex is 1.5 x 10(12); log K = 12.2. Beer's law was obeyed over the concentration range 0.01-0.34 mg/L. The Sandell sensitivity and relative standard deviation are 0.4 ng/cm2 and 2.6%, respectively. The results obtained spectrophotometrically were compared to those obtained by AAS analysis. The analytical parameters affecting flotation and hence determination have been thoroughly investigated. The proposed procedure was successfully applied to the determination of Cd(II) traces in certified and real human hair samples as well as in natural waters. The structure of the complex formed and the mechanism of flotation were proposed.


Subject(s)
Cadmium/analysis , Cadmium/chemistry , Phenanthrenes/chemistry , Spectrophotometry/methods , Thiosemicarbazones/chemistry , Calibration , Hair/chemistry , Humans , Hydrogen-Ion Concentration , Ions , Molecular Structure , Oleic Acid/chemistry , Sensitivity and Specificity , Solutions/chemistry , Temperature
7.
Chem Pharm Bull (Tokyo) ; 49(6): 664-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11411513

ABSTRACT

Copper(II) forms 1:1 and 1:2 intense red complexes with phenanthraquinone monophenylthiosemicarbazone (PPT) at pH 3-3.5 and > or =6.5, respectively. These complexes exhibit maximal absorbance at 545 and 517 nm, the molar absorptivity being 2.3 x 10(4) and 4.8 x 10(4) l mol(-1) cm(-1), respectively. However, the 1:1 complex was quantitatively floated with oleic acid (HOL) surfactant in the pH range 4.5-5.5, providing a highly selective and sensitive procedure for the spectrophotometric determination of CuII. The molar absorptivity of the floated Cu-PPT complex was 1.5 x 10(5) l mol)(-1) cm(-1). Beer's law was obeyed over the range 3-400 ppb at 545 nm. The analytical parameters affecting the flotation process and hence the determination of copper traces were reported. Also, the structure of the isolated solid complex and the mechanism of flotation were suggested. Moreover, the procedure was successfully applied to the analysis of CuII in natural waters, serum blood and some drug samples.


Subject(s)
Copper/analysis , Pharmaceutical Preparations/chemistry , Phenanthrenes/chemistry , Spectrophotometry/methods , Thiosemicarbazones/chemistry , Water/chemistry , Copper/chemistry , Humans , Hydrogen-Ion Concentration , Reproducibility of Results , Sensitivity and Specificity , Temperature
9.
Talanta ; 53(4): 749-60, 2001 Jan 05.
Article in English | MEDLINE | ID: mdl-18968164

ABSTRACT

The use of chemically modified chloromethylated polystyrene-PAN, CMPS-PAN (ion-exchanger) for the preconcentration and separation of total mercury after digestion in preparation for determination by cold vapour atomic absorption spectrometry (CVAAS) was described. The effects on the percentage of recovered mercury by mass change of ion-exchanger, stirring time, pH of the solution samples and eluent concentration were studied. The distribution coefficient K(d) is 10(6.6) ml g(-1). The interfering effects of some foreign ions were described. The metal complex formed between CMPS-PAN ion-exchanger and mercury was characterized by IR spectroscopy, pH-metric titration and thermal analysis. The method is simple and rapidly applicable for the determination of total mercury (ng ml(-1)) in natural water, milk and urine.

10.
Int J Radiat Oncol Biol Phys ; 48(2): 415-20, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-10974455

ABSTRACT

PURPOSE: To assess the role of chemoradiation as a primary treatment for vulvar carcinoma. METHODS AND MATERIALS: Between December 1989 and August 1997, there were 14 patients with the diagnosis of squamous cell carcinoma of the vulva. Two patients were excluded from this study because of advanced stage at presentation. Key information about the remaining 12 patients was extracted from their charts. All patients had biopsy prior to treatment, and were treated with chemoradiation. Radiation was administered to the vulva only. Surgical biopsies from the vulva and inguinal nodal dissection were done 4-6 weeks after radiation treatment. All patients were followed for evaluation of response and clinical detection of recurrence. The period of follow-up ranged from 8 to 125 months. Mean follow-up period was 41 months. RESULTS: All 12 patients showed complete response to the treatment. Only 1 patient (8.3%) developed local recurrence at 3 months posttreatment. Another patient (8.3%) developed nodal recurrence at 30 months posttreatment. Both patients were salvaged by surgical treatment and remained disease free. The actuarial 5-year disease-free survival was 43%. The actuarial 3-year disease-free survival was 84%. The majority of patients developed mild-to-moderate complications due to chemoradiation. These were well tolerated and responded to medical treatment. None of the patients developed late complications to chemoradiation treatment. CONCLUSIONS: Chemoradiation is an effective primary treatment for vulvar carcinoma as shown by these successfully managed cases.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Vulvar Neoplasms/drug therapy , Vulvar Neoplasms/radiotherapy , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Middle Aged , Mitomycin/administration & dosage , Neoplasm Staging , Vulvar Neoplasms/pathology
11.
APMIS ; 105(10): 773-83, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9368592

ABSTRACT

This work was designed to test whether hyporesponsiveness to schistosomal egg antigen (SEA) was associated with reduction in size of hepatic granulomas. Multiple small doses of SEA (10 micrograms x 4) were injected intravenously (i.v.) into C57B1/6 mice either at 7 or 30 days prior to cercarial exposure. Eight weeks postinfection, hepatic histopathology and granuloma diameter were studied. SEA-induced lympho-proliferative response, splenic cytokines (IL-2, IL-4 and IL-5) and serum antischistosomal IgG were assessed. Worm burden and tissue egg load were counted. Compared to infected controls, the SEA-treated groups showed decrease in granuloma diameter, remarkable increase in the percentage of degenerated ova within hepatic granulomas and amelioration of histopathological changes. SEA lymphoproliferative response, and levels of Il-2 and IL-4, were lower in SEA-treated groups than infected controls. The levels of IL-5 and antishistosomal IgG were comparable to the infected controls. The intensity of infection was not influenced by i.v. injection of SEA. The present data show that i.v. administration of multiple small doses of SEA induced granulomatous hyporesponsiveness with amelioration of hepatic pathology and acceleration of egg destruction.


Subject(s)
Antigens, Helminth/immunology , Schistosomiasis mansoni/immunology , Animals , Antibodies, Helminth/biosynthesis , Antigens, Helminth/administration & dosage , Dose-Response Relationship, Immunologic , Granuloma/immunology , Immunoglobulin G/immunology , Immunosuppression Therapy/methods , Injections, Intravenous , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Schistosomiasis mansoni/pathology , Solubility
12.
J Egypt Soc Parasitol ; 27(2): 563-70, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9257995

ABSTRACT

The prevalence of Helicobacter pylori in Egyptian patients with different stages of liver diseases was compared to those with normal liver status. Eighty patients subjected to upper gastrointestinal endoscopy were enrolled. They were divided according to their liver status into two groups; the first patients with liver cirrhosis and the second who had no liver affection. Gall bladder diseases were excluded by abdominal ultrasound examinations. Endoscopic antral mucosal biopsies were used for H. pylori screening by both culture and urease test, and for histopathological examinations. Both groups were matched as regards age, sex, and socioeconomic conditions. Culture was positive in 42.2% and 40.7% of patients in both groups respectively (P > 0.05). Urease test showed positive results in 58% and 76.6% in both groups respectively (P > 0.05). Helicobacter pylori prevalence showed no significant differences between both studied groups as regards age, sex, or type of gastric lesions. Furthermore, liver status in patients with chronic liver diseases does not play a role in distribution of infection. The study shows the high prevalence of H. pylori among Egyptians and the absence of a relation between H. pylori and chronic liver diseases.


Subject(s)
Helicobacter Infections/epidemiology , Helicobacter pylori , Liver Cirrhosis/complications , Adult , Egypt/epidemiology , Female , Gastritis/microbiology , Helicobacter Infections/complications , Humans , Liver Cirrhosis/microbiology , Male , Middle Aged , Prevalence , Socioeconomic Factors
13.
Ann Allergy Asthma Immunol ; 78(1): 41-4, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9012620

ABSTRACT

BACKGROUND: Immediate-type allergic reactions to latex products have become increasingly recognized in hospital workers. OBJECTIVE: This study was designed to assess the prevalence of latex sensitization by skin testing and specific IgE testing in a group of hospital employees and compare these with each subject's self-reported allergic history. METHODS: Volunteers were recruited from selected departments. Each was tested with epicutaneous skin test with latex glove extract and commercial environmental allergens, had blood drawn for latex-specific IgE testing (AlaSTAT brand of ELISA), and was given a questionnaire for general and latex allergy history. RESULTS: There were 135 participants. Eleven (8.2% of sample, 95% confidence interval 3.4% to 13.0%) were skin test positive for latex reagent, and seven of these (5.2% of sample) reported allergic symptoms to latex contact. Testing for latex-specific IgE (ELISA) showed 6.7% with class II or higher reaction. There was high correlation of the two tests, with ELISA showing a sensitivity of 63.6% and a specificity of 98.4% with reference to skin testing. In this sample, 16% reported some upper respiratory symptoms in association with latex contact, although only one-third of this group was skin test positive. Past history of allergic or atopic disease was poorly predictive of skin or blood test reactivity. A reaction to a greater number of environmental allergens was associated with positive latex skin test reactivity. CONCLUSION: Testing for latex sensitivity in this hospital sample revealed more than 5% of workers developed clinical allergies to latex and continued to remain occupationally in contact with latex. In vitro testing is a potential substitute for the more technically difficult skin testing.


Subject(s)
Hypersensitivity, Immediate/epidemiology , Latex/immunology , Occupational Diseases/epidemiology , Personnel, Hospital , Adult , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hypersensitivity, Immediate/immunology , Male , Middle Aged , Occupational Diseases/immunology , Pennsylvania , Prevalence , Radioallergosorbent Test , Skin Tests
14.
Haemostasis ; 27(1): 39-48, 1997.
Article in English | MEDLINE | ID: mdl-9097085

ABSTRACT

Some platelet alpha-granule contents were assessed in parallel with other markers of hemostatic imbalance in 50 patients with hepatosplenic schistosomiasis (15 patients with compensated hepatosplenomegaly, 15 patients with advanced hepatic fibrosis and ascites and 20 patients during an acute attack of hematemesis from ruptured esophageal varices). Platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), fibronectin (FN), prothrombin fragment 1 + 2, thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP) and D-dimer were assessed in schistosomal patients compared to controls (15 healthy subjects). A significant increase in both thrombin (high TAT and prothrombin fragment 1 + 2 levels) and plasmin (high FbDP and D-dimer levels) generation was detected in decompensated patients establishing the presence of a steady state of low-grade disseminated intravascular coagulation, with and without overt bleeding, in these patients. A decrease in plasma FN concentration was found in diseased groups compared to controls. The reduction in plasma levels of FN paralleled the defective liver function and matched the relative decrease in tissue FN in liver specimens of decompensated patients suggesting that FN levels can be used to evaluate the pathological staging of the disease. A significant increase in beta-TG and PF4 levels was noted in decompensated patients with ascites and/or acute hematemesis compared both to controls and compensated patients reflecting platelet alpha-granule release and consequently increased in vivo platelet activation which may initiate and/or perpetuate the pathophysiological mechanisms of the hemostatic imbalance underlying the hemorrhagic diathesis in hepatosplenic schistosomiasis.


Subject(s)
Fibronectins/blood , Hematemesis/blood , Liver Diseases, Parasitic/blood , Platelet Factor 4/chemistry , Schistosomiasis mansoni/blood , Splenic Diseases/blood , beta-Thromboglobulin/chemistry , Acute Disease , Adolescent , Adult , Female , Fibronectins/physiology , Hematemesis/etiology , Hematemesis/parasitology , Humans , Liver Diseases, Parasitic/pathology , Male , Middle Aged , Platelet Factor 4/physiology , Schistosomiasis mansoni/pathology , Splenic Diseases/parasitology , Splenic Diseases/pathology , beta-Thromboglobulin/physiology
15.
J Clin Pathol ; 49(12): 990-3, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9038736

ABSTRACT

AIM: To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis. METHODS: The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out. RESULTS: The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature. CONCLUSION: These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.


Subject(s)
Fibrin/metabolism , Fibrinolysis/physiology , Liver Diseases, Parasitic/metabolism , Schistosomiasis mansoni/metabolism , Adolescent , Adult , Ascites/metabolism , Ascites/physiopathology , Female , Fibrinolysin/metabolism , Hematemesis/metabolism , Hematemesis/physiopathology , Hepatitis, Viral, Human/complications , Hepatitis, Viral, Human/metabolism , Hepatitis, Viral, Human/physiopathology , Humans , Liver Diseases, Parasitic/complications , Liver Diseases, Parasitic/physiopathology , Male , Middle Aged , Plasminogen/metabolism , Schistosomiasis mansoni/complications , Schistosomiasis mansoni/physiopathology , Severity of Illness Index
16.
Int J Immunopharmacol ; 18(12): 707-18, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9172014

ABSTRACT

This study was undertaken to study the efficacy of praziquantel (PZQ) in potentially tolerized Schistosoma mansoni infected, egg-injected C57BL/6 mice, receiving multiple administrations of soluble egg antigen (SEA) intravenously (i.v.). Four animal groups were studied. Experimental group I received four injections of SEA (10 micrograms) intravenously on days -7, -5, -3 and -2 before infection and PZQ orally (500 mg/kg over two consecutive days 7 weeks post-infection. Three control groups received the following treatment: group II received the same tolerizing dose of SEA without PZQ, group III received PZQ in the same dose and at the same timing. Group IV received S. mansoni infection and egg injection 8 weeks post-infection and served as an infected, egg-injected control. Egg injection was conducted 8 weeks post-infection using viable S. mansoni eggs via the tail vein. Animals were killed 16 days post-egg injection, i.e. 10 weeks post-infection. After sacrifice, lungs and livers were removed for histopathological study and measurement of granuloma diameters. Spleens and serum were collected for the assay of lymphoproliferative response to SEA and antischistosomal immunoglobulins. The worm and egg burdens were also studied. Compared to infected, egg-injected untreated controls, repeated i.v. administrations of SEA down-regulated egg-injected (pulmonary) and egg-deposited (hepatic) granulomas and the lymphoproliferative response to SEA. Antischistosomal IgG level was increased. Susceptibility to S. mansoni infection was not found to be different from that in the infected, egg-injected controls. PZQ in the dose used caused complete eradication of worms, disappearance of immature egg stages, decrease in the number of mature eggs and an increase in the number of dead eggs. Hepatic granuloma diameter, lymphoproliferative response to SEA and IgG level were reduced. In mice receiving a combined regimen of multiple SEA administrations and PZQ with down-regulated granuloma and reduced lymphoproliferative response to SEA, the efficacy of PZQ was the same as in mice receiving PZQ alone. This was shown by comparable grades of worm and egg reduction. The histopathological examination of liver and lung sections in the different treated groups revealed moderate to small-sized hypocellular granulomas. Although no statistically significant difference was recorded between the mean granuloma diameters of the experimental group receiving both the tolerizing dose of SEA and PZQ compared to the group receiving the tolerizing dose of SEA without chemotherapy, this experimental group showed the least associated histopathological parenchymal changes. It appears from this work that combined SEA and PZQ provided many complementary goals; a reduction of egg-induced pathology, minimal parenchymal changes and the eradication of worms.


Subject(s)
Immunotherapy, Active/standards , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/prevention & control , Animals , Antibodies, Helminth/analysis , Antigens, Helminth/immunology , Antigens, Helminth/therapeutic use , Female , Granuloma/pathology , Immune Tolerance , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Liver/pathology , Liver Diseases/pathology , Lung/pathology , Lung Diseases/pathology , Mice , Mice, Inbred C57BL , Parasite Egg Count , Praziquantel/therapeutic use , Schistosoma mansoni/immunology
17.
Pharmacol Res ; 33(6): 319-25, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8971953

ABSTRACT

Colchicine alone or following praziquantel was given to mice infected with Schistosoma mansoni either 6 or 10 weeks post infection. Praziquantel increased body weight gain, histologically reduced number, diameter and cellularity of granuloma and improved liver function parameters. Early praziquantel therapy decreased hepatic collagen content as detected by the colorimetric method and the serum procollagen propeptide (PIIIP), while later treatment at the 10th week of infection increased hepatic collagen content and serum PIIIP. Colchicine therapy significantly decreased body weight gain with significant weight loss after early treatment. Colchicine did not change the histologic picture of schistosomal liver fibrosis; it induced a detectable hepatocytic injury recorded ultrastructurally and histologically with excitation of the inflammatory reaction in the granuloma and in portal tracts after early treatment. Excess pigmentation in macrophages and Kupffer cells, binucleation and large sized hepatocytic nuclei were evident after colchicine therapy. Colchicine increased hepatic collagen content microgram/mg protein, raised globulin and total serum protein and normalized the raised serum PIIIP of infected mice, but had no effect on PIIIP of normal mice. Early cessation of schistosomal infection evidently minimized the adverse effects of colchicine.


Subject(s)
Colchicine/therapeutic use , Liver Cirrhosis, Experimental/drug therapy , Liver Diseases, Parasitic/drug therapy , Praziquantel/therapeutic use , Schistosomiasis/drug therapy , Schistosomicides/therapeutic use , Animals , Body Weight/drug effects , Collagen/metabolism , Connective Tissue/parasitology , Female , Liver Cirrhosis, Experimental/parasitology , Liver Cirrhosis, Experimental/physiopathology , Liver Diseases, Parasitic/parasitology , Liver Diseases, Parasitic/physiopathology , Liver Function Tests , Mice , Organ Size/drug effects , Schistosomiasis/parasitology , Schistosomiasis/physiopathology
18.
Haemostasis ; 25(5): 218-28, 1995.
Article in English | MEDLINE | ID: mdl-7489960

ABSTRACT

Thrombin and plasmin generation were assessed in patients with endemic hepatosplenic schistomiasis (15 hepatosplenomegalic, 15 splenomegalic, 15 with advanced hepatic fibrosis and ascites and 15 hepatosplenic patients with hematemesis). Prolongation of prothrombin time, partial thromboplastin time and thrombin time, thrombocytopenia, hypofibrinogenemia, a decrease in antithrombin III and protein C and S levels and elevation in fibrinopeptide A, D-dimer and thrombin-antithrombin complex levels were detected in all groups. The deficit in hemostatic parameters was more pronounced with the advancement of the disease and was maximal in the hematemesis group. Our data demonstrate an increase in both thrombin and plasmin generation and indicate that low grade disseminated intravascular coagulation may occur in association with endemic Egyptian hepatosplenic schistosomiasis even in the steady state without overt bleeding.


Subject(s)
Disseminated Intravascular Coagulation/etiology , Schistosomiasis mansoni/complications , Adult , Ascites , Biopsy , Blood Coagulation Factors/analysis , Blood Coagulation Tests , Chronic Disease , Disseminated Intravascular Coagulation/blood , Egypt/epidemiology , Esophageal and Gastric Varices/blood , Esophageal and Gastric Varices/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Hepatomegaly/blood , Hepatomegaly/etiology , Hepatomegaly/pathology , Humans , Liver/pathology , Liver Cirrhosis/blood , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Male , Middle Aged , Schistosomiasis mansoni/blood , Schistosomiasis mansoni/epidemiology , Schistosomiasis mansoni/pathology , Severity of Illness Index , Splenomegaly/blood , Splenomegaly/etiology
20.
Int J Immunopharmacol ; 17(4): 291-302, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7672880

ABSTRACT

This study was undertaken to assess the optimum conditions required to reduce the vigorous host granulomatous reaction around Schistosoma mansoni eggs. Soluble schistosomal egg antigen (SEA) at a concentration of 10 or 100 micrograms protein was administered i.p. or i.v. into unprimed C57BL/6 mice. SEA was injected either alone or in combination with cyclophosphamide (CY) 100 or 50 mg/kg via i.p. route. Seven or 14 days later viable eggs of S. mansoni were injected via the tail vein into treated groups and untreated normal controls. Mice were sacrificed 8, 16 and 24 days after the injection of eggs. The lungs were removed for histopathological study, measurement of granuloma diameter and phenotypic analysis of granuloma intralesional T-cell subsets. Compared to untreated controls, the lower concentration of SEA (10 micrograms) administered by the i.v. route 7 days before egg injection, induced a significant reduction in granuloma diameter 16 days after egg injection than that by the i.p. route or at a higher SEA concentration (100 micrograms). Compared to untreated controls, the higher dose of CY (100 mg/kg), given i.p. alone or in combination with 10 micrograms SEA by the i.v. or i.p. route, induced a significant reduction in granuloma diameter, while 50 mg/kg CY did not cause any reduction. The reduction in granuloma diameter by i.v. administration of low SEA concentration alone or in combination with CY IP, was associated with a decrease in the granuloma intralesional L3T4+/Lyt2+ ratio. The decrease in the ratio was due to an increase in Lyt2+ cells. The results suggest that the use of low dose SEA by the i.v. route alone or combined with an immunosuppressive drug ameliorates pathological changes concurrent with S. mansoni infection.


Subject(s)
Antigens, Helminth/therapeutic use , Desensitization, Immunologic , Granuloma/prevention & control , Helminth Proteins , Lung Diseases, Parasitic/prevention & control , Schistosoma mansoni/immunology , Schistosomiasis mansoni/immunology , Animals , Antigens, Helminth/administration & dosage , Antigens, Helminth/immunology , Cyclophosphamide/therapeutic use , Granuloma/immunology , Granuloma/pathology , Host-Parasite Interactions , Injections, Intraperitoneal , Injections, Intravenous , Lung Diseases, Parasitic/immunology , Lung Diseases, Parasitic/pathology , Mice , Mice, Inbred C57BL , Schistosomiasis mansoni/pathology , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/pathology
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