Colonic adenocarcinoma and bilateral malignant ovarian sex cord tumor with annular tubules in Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is characterized by multiple polyps throughout the gastrointestinal tract in association with mucocutaneous pigmentation. Although Peutz-Jeghers syndrome polyps are hamartomas, frequent association of this syndrome with both gastrointestinal and non-gastrointestinal tumours had led to reassessment of the cancer risk in this hereditary disorder. The most common gynaecological tumors in this syndrome are adenoma malignum of the uterine cervix and ovarian sex cord tumor, particularly sex cord tumor with annular tubules. The question of malignant change in a polyp or of the association of gastro intestinal carcinomas still discuss. The authors report a case of Peutz-Jeghers syndrome in a young patient who developed a colonic adenocarcinoma in a hamartomatous polyp together with an incidentally discovered bilateral malignant sex cord tumours. We discuss its association with certain benign and malignant tumors and the risk of rare complications of these hamartomatous polyps. Although malignant tumors are increasingly reported in association with the Peutz-Jeghers syndrome, to our knowledge, there have been no previous reports of such an association in the literature.     

Autophagy mediates neutrophil responses to bacterial infection

Neutrophils constitute the first line of cellular defense against pathogens and autophagy is a fundamental cellular homeostasis pathway that operates with the intracellular degradation/recycling system. Induction of the autophagic process in neutrophils, in response to invading pathogens, constitutes a crucial mechanism in innate immunity. Exploration of autophagy has greatly progressed and diverse strategies have been reported for studying this molecular process in different biological systems; especially in infectious and inflammatory diseases. Furthermore, the role of autophagy in neutrophils, during pathogenic infection, continues to be of interest, due to the role of the cell in immunity function, its recruitment to the site of infection and its implication in inflammatory diseases. This review focuses on the known role of autophagy in neutrophils defence against pathogenic infections. A more detailed discussion will concern the recent findings highlighting the role of autophagy in inflammation and cell death in infected neutrophils.     

Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira

Background

Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities.

Methods

The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl.

Results

The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity.

Conclusion

The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising.     

Prognosis of periprosthetic regurgitation after mitral valve replacement using the Saint Jude prosthesis

Periprosthetic regurgitation (PPR) is a common complication of mitral valve replacement (MVR). The management of moderate and minor PPR remains controversial. The goal of this prospective study was to determine the incidence, predictors and outcome of PPR discovered using omniplan transoesophageal echocardiography (TEE) performed at the early postoperative period (14.7 days) of MVR with SJM prosthesis. Our study enrolled 56 patients, the mean age was 44.5 +/- 11.9 years. The incidence of PPR was 59% (33 patients). TEE showed one jet in nine patients (27%), two jets in 23 patients (70%) and three jets in one patient (3%). PPR is minor in 24 patients (63%) and moderate in nine patients (27%). No patient developed hemolytic anemia or congestive heart failure. In univariate analysis, diameter of prostheses > 27 mm, number of suture knots < 17 and diameter of prostheses/number of knot ratio > 1.7 independently predicted the presence of PPR. In multivariate analysis only a rapport diameter of protheses/number of suture knots > 1.7 mm is predictif of PPR (odd ratio = 9, P = 0.036). Ninety percent of PPR remained present at six weeks and only 29% were present after 12.5 months. CONCLUSION: Mild and minor PPR were frequent during the early postoperative period after MVR. The clinical significance and natural history is benign and they do not require any specific treatment.     

Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats

We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50–100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic–lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R₃) had a pronounced effect on the anti-inflammatory activity. Studies of structure–activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N ¹-phenyl-1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.     

Plasmodium falciparum causing hemophagocytic syndrome after allogeneic blood stem cell transplantation

We describe a case of Plasmodium falciparum infection in a 25-year-old male patient with a myelodysplastic syndrome, who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) in September 2003. Conditioning regimen consisted of total body irradiation (10 Gy) and cyclophosphamide 60 mg/kg for 2 days. A dose of 4 x 10(6) CD34+ cells/kg was transfused. Engraftment was well documented on day 17 post-transplantation. Spiking fevers occurred on days 19 and 21, associated with a pancytopenia, hepatosplenomegaly and neurological signs. P. falciparum parasites were found on the peripheral blood smear (parasitemia = 23%). Marrow aspiration showed P. falciparum parasites and proliferation of mature histiocytes with hemophagocytosis. Quinine 10 mg/kg i.v. three times a day for 10 consecutive days was given. The fever subsided within 3 days, and pancytopenia vanished in 14 days. Parasitemia cleared in 6 days. The patient left the unit on day 46 with no further complications. The screening of donors showed that infection was acquired from two blood units (from a single donor) given 5 days before transplantation. We report the first case of profound hemophagocytosis in immunosuppressed patient with malaria of high parasitemia after a bone marrow transplant.     

Antioxidant and UV-radiation absorption activity of aaptamine derivatives – potential application for natural organic sunscreens

Antioxidant and UV absorption activities of three aaptamine derivatives including piperidine[3,2-b]demethyl(oxy)aaptamine (C1), 9-amino-2-ethoxy-8-methoxy-3H-benzo[de][1,6]naphthyridine-3-one (C2), and 2-(sec-butyl)-7,8-dimethoxybenzo[de]imidazo[4,5,1-ij][1,6]-naphthyridin-10(9H)-one (C3) were theoretically studied by density functional theory (DFT). Direct antioxidant activities of C1–C3 were firstly evaluated via their intrinsic thermochemical properties and the radical scavenging activity of the potential antioxidants with the HOO˙/HO˙ radicals via four mechanisms, including: hydrogen atom transfer (HAT), single electron transfer (SET), proton loss (PL) and radical adduct formation (RAF). Kinetic calculation reveals that HOO˙ scavenging in water occurs via HAT mechanism with C1 (k_app, 7.13 × 10⁶ M⁻¹ s⁻¹) while RAF is more dominant with C2 (k_app, 1.40 × 10⁵ M⁻¹ s⁻¹) and C3 (k_app, 2.90 × 10⁵ M⁻¹ s⁻¹). Antioxidant activity of aaptamine derivatives can be classified as C1 > C3 > C2. Indirect antioxidant properties based on Cu(i) and Cu(ii) ions chelating activity were also investigated in aqueous phase. All three studied compounds show spontaneous and favorable Cu(i) ion chelating activity with ΔG⁰ being −15.4, −13.7, and −15.7 kcal mol⁻¹, whereas ΔG⁰ for Cu(ii) chelation are −10.4, −10.8, and −2.2 kcal mol⁻¹ for C1, C2 and C3, respectively. In addition, all compounds show UVA and UVB absorption; in which the excitations are determined mostly as π–π* transition. Overall, the results suggest the potential applications of the aaptamines in pharmaceutics and cosmetics, i.e. as a sunscreen and antioxidant ingredient.

Antioxidant and UV absorption activities of three aaptamine derivatives were theoretically studied by density functional theory (DFT) and time-dependent density functional theory (TD-DFT).     

New insights into the competition between antioxidant activities and pro-oxidant risks of rosmarinic acid

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO˙/CH₃OO˙ radical scavenging and Fe(iii)/Fe(ii) ion chelation were theoretically studied using density functional theory at the M05-2X/6-311++G(2df,2p) level of theory. First, four antioxidant mechanisms including hydrogen atom transfer (HAT), radical adduct formation (RAF), proton loss (PL) and single electron transfer (SET) were investigated in water and pentyl ethanoate (PEA) phases. Regarding the free radical scavenging mechanism, HAT plays a decisive role with overall rate coefficients of 1.84 × 10³ M⁻¹ s⁻¹ (HOO˙) and 4.49 × 10³ M⁻¹ s⁻¹ (CH₃OO˙) in water. In contrast to PL, RAF and especially SET processes, the HAT reaction in PEA is slightly more favorable than that in water. Second, the [Fe(iii)(H₂O)₆]³⁺ and [Fe(ii)(H₂O)₆]²⁺ ion chelating processes in an aqueous phase are both favorable and spontaneous especially at the O5, site-1, and site-2 positions with large negative Δ_rG⁰ values and great formation constant K_f. Finally, the pro-oxidant risk of RA⁻ was also considered via the Fe(iii)-to-Fe(ii) complex reduction process, which may initiate Fenton-like reactions forming reactive HO˙ radicals. As a result, RA⁻ does not enhance the reduction process when ascorbate anions are present as reducing agents, whereas the pro-oxidant risk becomes remarkable when superoxide anions are found. The results encourage further attempts to verify the speculation using more powerful research implementations of the antioxidant activities of rosmarinic acid in relationship with its possible pro-oxidant risks.

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO˙/CH₃OO˙ radical scavenging and Fe(iii)/Fe(ii) ion chelation were theoretically studied using density functional theory at the M05-2X/6-311++G(2df,2p) level of theory.     

Allogenic bone marrow transplantation complications. Part II

Bone marrow transplantation increase the chances of cure of many hematology and also neoplasms cancers. The procedure is however a cause of expected mortality and morbidity. The complications are represented by mucocutaneous, toxicity graft versus host disease, veno-occlusive disease and most importantly injections consequences all this complications needs to be prevented and treated considering the risk associated to the moderling immunosuppression.