Bioactivity of Trigonella foenum (Fenugreek) oil on immunological and biochemical response of Schistosoma mansoni infected mice.

The effect of fenugreek oil (FO) on some parasitological, immunological, and biochemical parameters in mice infected with Schistosoma mansoni were investigated. Chromatography mass spectrometry (GC/MS) analysis of FO revealed that linoleic acid, (E,E)-4-decadienal, and isopropyl myristate are the major constituents of FO. The results showed that treatment of S. mansoni-infected mice with 0.15 ml of FO daily for 10 successive days exhibited a significant reduction in the number of S. mansoni male worms, and coupled worms as compared to an infected control group (p < 0.05). Regarding total egg counts and oogram patterns, FO effectively reduced the percentage of hepatic and intestinal egg counts, and elevated immature and dead eggs in ratios closely to praziquantel (PZQ) treated mice. Meanwhile, FO significantly elevated the levels of glutathione and co-enzyme Q-10 (COQ-10) up to 0.33±0.02 ng/ml and 0.28±0.02 ng/ml, respectively. However, when accompanied with PZQ, COQ-10 level was closer to that of the normal control group (0.37 ± 0.021 ng/ml). The result also showed that FO significantly reduced levels of lipid per-oxidation (0.165±0.01 ng/ml) and vascular endothelial growth factor (0.25±0.02 pg/ml) as compared to the PZQ-treated group (0.234±0.02 ng/ml and 0.31±0.008 pg/ml, respectively). Moreover, FO recovered normal values of caspase-7, and when accompanied with PZQ, annexin-V was also significantly reduced. However, treatment of S. mansoni-infected mice with PZQ led to a significant increase in the level of annexin-V as compared to S. mansoni-infected mice group (p < 0.05). It can be concluded that FO may have a potential anti-schistosomal, antioxidant and anti-inflammatory activities. Also, it may have a recovering effect on apoptotic parameters toward the normal values.

10 years of experience in adopting, implementing and evaluating progress testing for Saudi medical students.

Objectives: The progress test (PT) is a comprehensive examination that is designed to match the knowledge acquisition necessary at graduation and monitors progress during the entire period of an undergraduate program. Qassim College of Medicine (QCM) began using the multi-institutional PT in the Kingdom of Saudi Arabia (KSA). This study aimed to determine if the PT can be utilized to assess the progress of medical students at different Saudi medical colleges with different educational approaches, as well as whether this testing modality could be accepted by other colleges. Methods: Beside the establishment of a PT committee, comprehensive blueprinting was crafted to sample 200 A-type multiple choice questions (MCQs) from different disciplines. The PT is a paper-and-pencil model and is answered in a 4-h period. All PT items followed a uniform design. Results: In total, 13 rounds of the progress test have been conducted. The number of participating colleges increased from three (with 285 students) in the first test (May 2012) to more than 20 (with >6000 students) in the ninth round (February 2017). The average % scores for first-year students ranged from 3.0% to 7.9% while the average scores for fifth-year students ranged from 34.0% to 43.0%. Conclusion: The conduction of this meticulously crafted test to evaluate knowledge achievement at medical graduation is a fruitful tool and helps to provide constructive feedback for test-takers and other stakeholders relating to their relative positions among other fellows at the national level.

Expression and prognostic relevance of long noncoding RNAs CRNDE and AOX2P in adult acute myeloid leukemia.

INTRODUCTION: Several long noncoding RNAs (lncRNAs) have been demonstrated to play a critical role in the tumorigenesis of acute myeloid leukemia (AML), and altered expression of certain lncRNAs has been recognized as a potential prognostic marker in AML patients. Here, we sought to determine whether the expression of the lncRNA colorectal neoplasia differentially expressed (CRNDE) and aldehyde oxidase 2 pseudogene (AOX2P) is associated with clinicopathological features and clinical outcome of patients with AML. METHODS: CRNDE and AOX2P expression levels were measured in diagnostic blood samples from 200 adult patients with de novo AML, along with 50 healthy control blood samples, using quantitative real-time polymerase chain reaction (qRT-PCR). The association of CRNDE and AOX2P expression with the clinicopathological characteristics and outcome of AML patients was analyzed. RESULTS: Upregulated CRNDE expression was independently associated with lower complete remission (CR) rates in the whole cohort of AML (P < .001). AOX2P overexpression was identified as an independent adverse prognostic marker for CR in the CN-AML (P = .009) and non-t (15;17) AML (P < .001) subgroups. Patients with high CRNDE expression had a significantly shorter event-free survival (EFS, whole cohort of AML: P = .017; CN-AML: P = .001; non-t (15;17) AML: P = .006) and inferior overall survival (OS, whole cohort of AML: P = .002; t(15;17) AML: P = .001) than those with low CRNDE expression. EFS and OS did not differ significantly between patients with high AOX2P expression and those with low expression. CONCLUSION: Aberrantly upregulated CRNDE expression and, to a lesser extent, AOX2P overexpression, are associated with poor prognosis in AML patients, suggesting that the determination of CRNDE and, perhaps, AOX2P, expression level at diagnosis provides valuable prognostic information, allows refinement of risk stratification, and helps clinical decision-making in AML.

Antioxidant enzyme activities and immune responses in rainbow trout (Onchorhynchus mykiss) juveniles fed diets supplemented with dandelion (Taraxacum officinalis) and lichen (Usnea barbata) extracts.

In the present study, antioxidant activity, immune responses, and growth performance of rainbow trout (Onchorhynchus mykiss) juveniles fed with diets supplemented with dandelion (Taraxacum officinalis) and lichen (Usnea barbata) extracts were assessed. Four different concentrations of aqueous methanolic extract of the plants (0% (control), 0.1%, 0.5%, and 1% (D, dandelion; L, lichen) were added to the diets, and fish were fed for 75 days. On the 15th, 45th, and 75th day of the study, liver antioxidant enzyme activities were determined, and immune responses were determined every 15th day. The results showed that SOD activity increased in the fish group of 0.1% D on the 15th and 45th day compared to control; however, it was lower in all the lichen extract-treated groups than in control at almost all sampling times, except on the 15th day in the 0.1% L group. CAT activity showed an increased value (P < 0.05) in 0.5% L and 1% L treated fish groups on the 15th day, in fish of 1% D and 1% L groups on 45th and on 75th day in 0.1% D group. GPX activity increased on the 15th day of the study in fish of 0.1% D group, on the 45th day in 1% D and 1% L groups and on the 75th day in fish of 0.5% D, 0.1% D, and 0.5% L groups (P < 0.05). G6PDH enhanced in all treatment groups compared to control on the 15th day, except in 0.1% L and 0.5% L groups. An elevated G6PDH activity was also observed on the 75th day of the study in 0.5% D, 1% D, and 0.5% L fish groups. An increase on lipid peroxidation (LP) was observed in all L groups on the 45th day of the study. Lysozyme activity was determined to be the highest in 0.5% and 1% L on the 45th day, in 0.1% L on the 60th day and in the 0.5% L fish group on the 75th day compared to control (P < 0.05). Myeloperoxidase was found to be the highest at the end of the study in 1% L fish group compared to the control (P < 0.05). In conclusion, we suggest the use of dandelion to combat oxidative stress and to lower FCR and the use of lichen to modulate the immune response in rainbow trout. The use of such products will be economical for aquaculture and harmless for the environment.

Effect of Intracavernosal Injection of Prostaglandin E1 on Duration and Rigidity of Erection in Patients With Vasculogenic Erectile Dysfunction: Is It Dose Dependent?

OBJECTIVE: To assess if the effect of intracavernosal injection of prostaglandin E1 (PGE1) on duration and rigidity of erection is dose dependent in patients with different types of vasculogenic erectile dysfunction (ED)? METHODS: A hundred patients with ED were assigned into 4 groups (n = 25/each); group (A) patients with arteriogenic ED, group (B) patients with veno-occlusive ED, group (C) patients with mixed (arteriogenic and veno-occlusive) ED, and group (D) patients who have only psychogenic ED (control). After intracavernosal injection of PGE1, patients were assessed using penile Doppler ultrasonography and erection hardness score together with calculation of erection duration. The starting dose of PGE1 was 5 µg which was increased to 10 µg and 20 µg as a maximal dose when needed. RESULTS: The mean PSV of patients in groups A, B, C, and D were 24.38 ± 3.3, 37.74 ± 8.28, 22.24 ± 3.85, and 47.76 ± 6.27, respectively. In group D, 88% have achieved the best response at dose of 5 µg while 5.3%, 21.7%, and 0% have achieved the best response at dose of 5 µg in groups A, B, and C, respectively (P < .05 for each). The rest of patients have required either 10 or 20µg to achieve the best response. Patients in group C have required the highest dose of PGE1 to achieve the best response (P < .05). CONCLUSION: Intracavernosal injection of PGE1 in escalating doses have improved the rigidity and duration of erection in patients with different types of vasculogenic ED. Patients with mixed arteriogenic and veno-occlusive ED have required the highest dose of PGE1 to achieve the best response.

Alpinia zerumbet (Pers.): Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities.

BACKGROUND/AIM: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers. METHODS: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model. RESULTS: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively. CONCLUSION: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.

Correlation between angiogenic/inflammatory mediators in Wister rat model of liver dysplasia.

Angiogenesis plays a critical role in tumor development and progression. It is regulated through the elaboration of many inflammatory/angiogenic mediators. In this study, we followed angiogenesis in hepatocarcinogenesis process from cancer initiation to sever dysplasia by measuring several inflammatory/angiogenic mediators. Wister rat model of liver cancer was set up using diethylnitrosamine (DEN). One hundred twenty rats were divided into 7 groups: normal untreated and 1- to 6-month DEN-treated animals. Every month, group of DEN-treated animals were sacrificed. Histopathological examination of livers was done. Plasma levels of vascular endothelial and platelet derived growth factors (VEGF and PDGF), interleukin-8 (IL-8), IL-4, tumor necrosis factor (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay (ELISA). Histopathological findings were confirmatory to the gradual formation of liver cancer with time (from mild to moderate to irreversible severe dysplasia). Increase in angiogenic (VEGF and IL-8) (P < 0.001) and inflammatory (IL-4 and COX-2) (P < 0.001) mediators were observed. Elevation in TNF-α and PDGF secretion levels was recorded after 3 months of DEN injection (P < 0.001). Our data stressed on the importance of inflammation/angiogenesis processes in dysplasia. The exact regulatory mechanisms of liver cancer remain to be clarified.

Adaptation of the Agrobacterium tumefaciens VirG response regulator to activate transcription in plants.

The Agrobacterium tumefaciens VirG response regulator of the VirA/VirG two-component system was adapted to function in tobacco protoplasts. The subcellular localization of VirG and VirA proteins transiently expressed in onion cells was determined using GFP fusions. Preliminary studies using Gal4DBD-VP16 fusions with VirG and Escherichia coli UhpA, and NarL response regulators indicated compatibility of these bacterial proteins with the eukaryotic transcriptional apparatus. A strong transcriptional activator based on tandem activation domains from the Drosophila fushi tarazu and Herpes simplex VP16 was created. Selected configurations of the two-site Gal4-vir box GUS reporters were activated by chimeric effectors dependent on either the yeast Gal4 DNA-binding domain or that of VirG. Transcriptional induction of the GUS reporter was highest for the VirE19-element promoter with both constitutive and wild-type VirG-tandem activation domain effectors. Multiple VirE19 elements increased the reporter activity proportionately, indicating that the VirG DNA binding domain was functional in plants. The VirG constitutive-Q-VP16 effector was more active than the VirG wild-type. In both the constitutive and wild-type forms of VirG, Q-VP16 activated transcription of the GUS reporter best when located at the C-terminus, i.e. juxtaposed to the VirG DNA binding domain. These results demonstrate the possibility of using DNA binding domains from bacterial response regulators and their cognate binding elements in the engineering of plant gene expression.

Role of cysteinyl leukotriene receptor-1 antagonists in treatment of experimentally induced mammary tumor: does montelukast modulate antitumor and immunosuppressant effects of doxorubicin?

It has been reported that a leukotriene (LT)-D4 receptor (i.e. cysteinyl LT1 receptor; CysLT1R) has an important role in carcinogenesis. The current study was carried out to assess the possible antitumor effects of montelukast (MON), a CysLT1R antagonist, in a mouse mammary carcinoma model, that is, a solid Ehrlich carcinoma (SEC). Effects of MON on tumor-induced immune dysfunction and the possibility that MON may modulate the antitumor and immunomodulatory effects of doxorubicin (DOX) were also studied. The effects in tumor-bearing hosts of several dosings with MON (10 mg/kg, per os), with and without the added presence of DOX (2 mg/kg, intraperitoneal), were investigated in vivo; end points evaluated included assessment of tumor volume, splenic lymphocyte profiles/functionality, tumor necrosis factor-α content, as well as apoptosis and expression of nuclear factor-κB (NF-κB) among the tumor cells. The data indicate that MON induced significant antitumor activity against the SEC. MON treatments also significantly mitigated both tumor- and DOX-induced declines in immune parameters assessed here. Moreover, MON led to decreased NF-κB nuclear expression and, in doing so, appeared to chemosensitize these tumor cells to DOX-induced apoptosis.

PPARγ-dependent anti-tumor and immunomodulatory actions of pioglitazone.

Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to play important roles in carcinogenesis. The current study was carried out to assess the possible anti-tumor effects of pioglitazone (PIO), a PPARγ agonist, in a mouse mammary carcinoma model, i.e. a solid Ehrlich carcinoma (SEC). Effects of PIO on tumor-induced immune dysfunction, and the possibility that PIO may modulate the anti-tumor and immunomodulatory effects of doxorubicin (DOX) were also studied. The effects in tumor-bearing hosts of several doses of PIO (100 mg/kg, per os), with and without the added presence of DOX (2 mg/kg, IP), was investigated in vivo; end-points evaluated included assessment of tumor volume, splenic lymphocyte profiles/functionality, tumor necrosis factor (TNF)-α content, as well as apoptosis and expression of nuclear factor-κB (NF-κB) among the tumor cells. The data indicate that PIO induced significant anti-tumor activity against the SEC. PIO treatments also significantly mitigated both tumor- and doxorubicin-induced declines in immune parameters assessed here. Moreover, PIO led to decreased NF-κB nuclear expression, and, in doing so, appeared to chemo-sensitize these tumor cells to DOX-induced apoptosis. All pioglitazone-studied effects were antagonized by GW9662, a selective PPARγ antagonist.

The hepatoprotective activity of blue green algae in Schistosoma mansoni infected mice.

This study aims to evaluate the immunomodulatory effects of a natural product, blue green algae (BGA) (100 mg/kg BW), alone or combined with praziquantel PZQ (250 mg/kg BW) on granulomatous inflammation, liver histopathology, some biochemical and immunological parameters in mice infected with Schistosoma mansoni. Results showed that the diameter and number of egg granuloma were significantly reduced after treatment of S. mansoni-infected mice with BGA, PZQ and their combination. The histopathological alterations observed in the liver of S. mansoni-infected mice were remarkably inhibited after BGA treatments. BGA decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as well as the level of total protein (TP) while the level of albumin was increased. Treatment of infected mice with BGA, PZQ as well as their combination led to significant elevation in the activities of hepatic antioxidant enzymes glutathione peroxidase (GPX) and glutathione-S-transferase (GST) as compared with control group. Combination of BGA and PZQ resulted in significant reduction in the level of intercellular adhesion molecules-1 (ICAM-1), vascular adhesion molecules-1 (VCAM-1) and tumor necrosis factor-alpha (TNF-α) when compared to those of the S. mansoni-infected group. Overall, BGA significantly inhibited the liver damage accompanied with schistosomiasis, exhibited a potent antioxidant and immunoprotective activities. This study suggests that BGA can be considered as promising for development a complementary and/or alternative medicine against schistosomiasis.

Circulating pro- and anti-angiogenic mediators in patients infected with hepatitis C at different stages of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by neovascularization. The objective of the current study was to determine circulating proangiogenic [vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and tumor necrosis factor (TNF-α)] and antiangiogenic [IL-4, IL-12, interferon gamma-induced protein 10 (IP-10), and angiostatin] factors in Egyptian patients with different stages of HCC. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of these mediators in plasma of 135 HCC patients (57 Child-Pugh A, 24 Child-Pugh B, and 54 Child-Pugh C stage) and 50 healthy subjects. Results showed a significant increase in plasma levels of VEGF (P < 0.001), PDGF (P < 0.001), TNF-α (P < 0.01), angiostatin (P < 0.01), and IP-10 (P < 0.001) and a significant reduction in IL-12 (P < 0.001) in HCC patients in relation to normal controls. Classifying HCC patients based on their Child-Pugh's score revealed that the maximum production of proangiogenic mediators (VEGF and TNF-α) was present in HCC patients with Child-Pugh C score which coincides with maximum reduction in antiangiogenic mediators (IL-4, IL-12, and angiostatin). Taken together, these results indicated that the determination of these factors in different Child-Pugh's scores of HCC might be an important guide in clinical decision making regarding therapy and outcome.

Effect of cadmium-polluted water on plasma levels of tumor necrosis factor-α, interleukin-6 and oxidative status biomarkers in rats: protective effect of curcumin.

UNLABELLED: The present study was designed to investigate the effect of CdCl2-polluted drinking water (40 mg CdCl2/L) on the level of TNF-α and IL-6, as well as oxidative status biomarkers in plasma of rats. The possible protective effect of oral administration of curcumin (50 mg/kg body weight/day) was assessed. Results illustrated that Cd exposure significantly elevated the plasma levels of TNF-α and IL-6 (p<0.001) as compared to normal rats. Also, Cd administration resulted in a significant elevation in the lipid peroxidation and markedly reduction in the activities of SOD and catalase as well as the level of glutathione and total antioxidant capacity in plasma. The co-treatment of Cd with curcumin significantly reduced the levels of TNF-α and IL-6 and ameliorated the alteration in oxidative status biomarkers induced by Cd. Negative correlation between IL-6 or TNF-α was and the plasma activities of catalase, SOD and the level of total antioxidant capacity were found in rats exposed to Cd. CONCLUSION: Cadmium toxicity induced the release of TNF-α and IL-6 which is associated with systemic oxidative stress. This may be involved in the mechanism of the Cd toxicity. On the other hand, the findings suggest the curative action of curcumin against Cd toxicity.

Tumor necrosis factor-α -308 G/A and interleukin 10 -1082 A/G gene polymorphisms in patients with acne vulgaris.

BACKGROUND: Cytokines play an important role in the pathogenesis of acne vulgaris together with other genetic and environmental factors. OBJECTIVE: To check for the association of TNF-α and IL-10 gene polymorphisms with the susceptibility and severity of acne in Saudi patients. SUBJECTS AND METHODS: Study subjects included 166 Saudi patients (65 males, 101 females) with acne vulgaris. Their mean age±SD was 21.6±5.1 years. These cases were compared to 390 unrelated healthy controls (208 males, 182 females) with a mean age±SD of 20.1±3.3 years. Cases were sub-grouped on the basis of their severity of acne affection into mild, moderate and severe groups. For all participants, genotypic variants of the TNF-α -308 G/A and IL-10 -1082 A/G genes were determined using the real time PCR technique. RESULTS: Frequencies of genotypic variants of the TNF-α -308 polymorphism were significantly different in acne cases compared to controls. Further analysis showed that acne cases had significantly higher frequency of both the GG and AA homozygous forms than controls (73.8% vs. 63.6%, p=0.02, odds ratio=1.6). It was also interestingly noticed that the amount of GG homozygosity was notably higher among female cases than male ones (76.0% vs. 54.7%, p=0.006, odds ratio=2.6) whereas male cases had a higher frequency of AA and GA genotypes than female ones (9.4% and 35.9% vs. 4% and 20% respectively). Differences in the frequencies of IL-10 -1082 genotypic variants were statistically insignificant comparing cases to controls (p=0.3). On the other hand, comparing cases-subgroups in terms of the age of onset of the disease, consanguinity, family history, obesity and acne severity; no statistical significance was observed regarding frequencies of genotypic variants related to the both TNF-α -308 and IL-10 -1082 polymorphisms (>0.05). CONCLUSIONS: TNF-α -308 polymorphic variants might be a predisposing factor for acne susceptibility, with no apparent relation to its severity whereas IL-10 -1082 variants showed no association with both acne susceptibility and severity.

Serum concentrations of cyclooxygenase-2 in patients with systemic sclerosis: association with lower frequency of pulmonary fibrosis.

Systemic sclerosis (SSc) is a multisystem disease in which interplay between inflammation, autoimmunity and fibrosis appears to play an indispensable role. Owing to the suggested role of cyclooxygenase-2 enzymes (Cox-2) in inflammation and fibrosis, we investigated their serum concentrations in SSc patients and their clinical and laboratory associations. Serum from 49 patients with SSc, 28 of whom had limited cutaneous SSc (lSSc) and 21 had diffuse cutaneous SSc (dSSc) subtypes, and from 27 healthy subjects were assayed for Cox-2 and TNF by enzyme-linked immunosorbent assay (ELISA). Demographic, clinical, autoantibodies and serological data were prospectively assessed. The analysis revealed that patients with lSSc had higher levels of serum Cox-2 than controls. Serum Cox-2 levels were increased in SSc patients with arthritis and digital ulcers; on the contrary, these were diminished in those with associated pulmonary fibrosis. An additional prospective large scale, longitudinal study should be carried out to support these findings and to reveal the mechanistic connections between Cox-2 levels and SSc disease manifestations.

Short report: prevalence of Neospora caninum and Toxoplasma gondii antibodies in northern Egypt.

In view of the worldwide importance of Toxoplasma gondii and Neospora caninum and the limited data on the seroprevalence of these parasites in Egypt, this study aimed to estimate the prevalence of anti-T. gondii and anti-N. caninum antibodies in rabbits, cattle, and humans. We used ELISA methods based on surface antigen 2 of T. gondii (TgSAG2t) and surface antigen 1 of N. caninum (NcSAG1t). High seroprevalence of T. gondii (51.49%) was detected in pregnant women, and antibodies to N. caninum were also detected in human samples (7.92%). Anti-T. gondii or N. caninum antibodies were detected in cattle (TgSAG2t: 10.75%; NcSAG1t: 20.43%). In rabbits, only one sample was N. caninum positive (1.85%). The high prevalence of toxoplasmosis and neosporosis in cattle affects the development of the livestock industry and is also an important infective source for human infection in Egypt.

Design, synthesis and antitumor evaluation of novel thalidomide dithiocarbamate and dithioate analogs against Ehrlich ascites carcinoma-induced solid tumor in Swiss albino mice.

A series of 16 novel thalidomide sulfur analogs containing one and two sulfur atoms 2 and 4-18, respectively, were designed and synthesized. These compounds were screened for in vitro antitumor activity against Ehrlich ascites carcinoma (EAC) cell line and exhibited potent cytotoxic activity. On the bases of the obtained results for in vitro cytotoxic activity, thalidomide sulfur analogs containing two sulfur atoms 8, 9, 13 and 14 were selected and tested in vivo against EAC-induced solid tumor in female mice compared to thalidomide 1 as well as its analog 2 and exhibited a highly significant reduction in tumor volume (TV). Results illustrated the antioxidative activity of these compounds as the level of hepatic lipid peroxidation decreased and levels of antioxidant enzymes like superoxide dismutase (SOD) and catalase were elevated. The histopathological investigations revealed that thalidomide sulfur analogs 2, 8, 9, 13 and 14 have antimitotic, apoptotic and necrotic activities against solid tumor. These compounds lead to increase of Fas-L expression. The immunohistochemical studies showed a decrease in Ki67 and vascular endothelial growth factor (VEGF) staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate and angiogenic process associated with tumor growth. Compounds 9 and 13 were the most potent compounds in tumor necrosis without liver necrosis. At the same time, treatment with compound 9 resulted in liver degeneration.

Rapid and efficient synthesis of 4-substituted pyrazol-5-one under microwave irradiation in solvent-free conditions.

New heterocyclic compounds containing pyrazol-5-one coupled with benzimidazole, benzothiazole, benzoxazole, quinoline, naphthyridin, and pyrazole were synthesized. Comparative investigations to synthesize these interesting classes of heterocyclic compounds through conventional heating or under microwave-irradiation conditions were presented. Synthesized compounds 1a, 2a, 4k, 3a, c, 5a, b, 6b, 7a, b, d, 8a, and 9a were evaluated for their antitumor activity. Some of these compounds exhibited promising antitumor activity.

Prospective, five-year follow-up study of patients with symptomatic uncomplicated diverticular disease.

PURPOSE: The natural history of diverticular disease is largely unknown. Most studies are retrospective and treatment recommendations are derived from outdated literature. This study was a prospective, long-term assessment of the development of complications in patients with symptomatic diverticular disease. METHODS: All patients with a confirmed diagnosis of symptomatic diverticular disease between August 1999 and April 2001 were followed up prospectively for an average of five years. Hospital computerized discharges were assessed for any subsequent elective or emergency admission for diverticular disease-related complications, including surgical intervention. A telephone questionnaire was conducted on all patients and/or their family physician looking specifically for symptoms, complications, and surgical intervention. RESULTS: A total of 163 patients (106 females) were identified (median age, 74 (interquartile range, 64-80) years). The diagnosis was confirmed through colonoscopy (n = 106), flexible sigmoidoscopy (n = 57), and barium enema (n = 31). Nineteen were lost to follow-up and a further 19 died from unrelated causes. Twenty-five were excluded. After the initial diagnosis, two patients (1.7 percent) subsequently presented with an episode of diverticulitis, which was treated conservatively. A single patient (0.8 percent) required surgery for chronic symptoms. One hundred sixteen patients (97 percent) had no or mild symptoms after a median follow-up of 66 months. CONCLUSIONS: In this prospective long-term study, symptomatic uncomplicated diverticular disease seems to run a long-term benign course with a very low incidence of subsequent complications. Symptomatic disease, acute diverticulitis, and complicated diverticular disease seem to constitute distinct clinical entities with little crossover between groups.