Toll-like receptor 9 negatively related to clinical outcome of AML patients.

BACKGROUND: Acute myeloid leukemia (AML) can modulate toll-like receptor-9 (TLR9) expression and activation. This study was conducted to elucidate the expression of TLR9 in AML patients and its relation to the prognosis of the disease. RESULTS: The study included 40 newly diagnosed AML patients managed in the hospital in addition to 20 sex and age matched normal volunteers as control. TLR9 expression assay was conducted on peripheral blood samples of AML cases before the start of treatment as well as the controls by immunophenotyping. TLR9 expression was ranging from 0.10 to 2.40% in AML patients with higher expression among the control, ranging from 0.94 to 8.25%. The median TLR9 expression in AML patients was significantly lower with advanced cytogenetic risk score. It is not significantly differing in relation to patients' sex, age group, and FAB type of AML. However, significant lower median expression was found in relation to clinical outcome. TLR9 expression ≤ 1% showed lower median overall survival time when compared to those with > 1% expression. CONCLUSION: This study concluded that AML patients express TLR9 in leukemic cells with very low percentage. This expression was negatively related to the clinical outcome.

Turkey 2017 Clinical Practice Guidelines on recommendations for screening diagnosing and managing hepatitis C virus.

The present guideline updates the Turkish recommendations for the screening, diagnosis and management of Hepatitis C virus (HCV) infection prepared by the Turkish Association for the Study of the Liver (TASL) and Viral Hepatitis Society (VHS). The aim of this guidance was to provide updates recommendations to physicians, who are interested in HCV care on the optimal screening, diagnosis and pre-treatment management for patients with HCV infection in Turkey. These recommendations, produced by panel experts, were aimed to addresses the management issues ranging from diagnosis and linkage to care, to the optimal treatment regimen in patients with HCV infection. Recommendations are based on evidence and opinions of more than 70% of the panelists. This guidance is supported by the memberships of two societies and not by pharmaceutical companies. This guidance will be updated frequently as new data become available.

Inhibiting the color formation by gradient temperature-elevating Maillard reaction of soybean peptide-xylose system based on interaction of l-cysteine and Amadori compounds.

Light color and savory flavor enhancer are attractive for consumers and food producers. The effect of addition time of l-cysteine on inhibiting color formation was investigated in soybean peptide-xylose system, and the possible pathway was explored. Once dicarbonyl compounds were formed during the Maillard reaction, the addition of l-cysteine had no color-inhibiting effect; if l-cysteine was added immediately after the Amadori compound was formed, the extraordinary color-inhibiting effect was observed. Therefore, an improved way to inhibit color formation was proposed on the basis of the interaction of l-cysteine and Amadori compounds by controlling the addition time of l-cysteine through gradient temperature-elevating Maillard reaction. The system was heated at 80 °C for 60 min to form Amadori compounds, followed by the addition of L-cysteine, and the temperature was raised to 120 °C and held for 110 min. Compared with traditional products, the lightest color product was found desirable by GC/MS analysis and sensory evaluation. The novel method proposed can be a guide for the industrial preparation of light-colored products.

Laser induced photocatalytic degradation of hazardous dye (Safranin-O) using self synthesized nanocrystalline WO3.

The photocatalytic degradation of Safranin-O (known as Basic Red 2) in water using locally synthesized nanocrystalline WO(3) as a photocatalyst was investigated under UV laser irradiation. The photo-oxidation removal of the dye was monitored by UV-vis spectrophotometer. The blank experiments for either laser irradiated only Safranin-O solution or the suspension containing WO(3) and Safranin-O in the dark showed that both laser illumination and the photocatalyst were essential for the removal of Safranin-O. The effect of experimental parameters including laser energy, catalyst loading, solution pH and the initial dye concentration on photocatalytic degradation of Basic Red 2 were also investigated. Results indicate that the rate of reaction is strongly influenced by the adsorption of an azo dye into the surface of the photocatalyst materials and suggests an optimum catalyst loading and dye concentration for the degradation reaction. It was investigated that the adsorption of the dye decreases at higher alkaline pH because both catalyst and substrate are negatively charged, developing repulsive forces between them. Kinetic data obtained reveals that the rate of the reaction obeys the first-order kinetics.

Laser-induced removal of a dye C.I. Acid Red 87 using n-type WO3 semiconductor catalyst.

Water contamination by organic substances such as dyes is of great concern worldwide due to their utilization in many industrial processes and environmental concerns. To cater the needs for waste water treatment polluted with organic dyes, laser-induced photocatalytic process was investigated for removal of a dye derivative namely Acid Red 87 using n-type WO3 semiconductor catalyst. The degradation was investigated in aqueous suspensions of tungsten oxide under different experimental conditions using laser instead of conventional UV lamp as an irradiation source. The degradation process was monitored by measuring the change in dye concentration as a function of laser irradiation time by employing UV spectroscopic analysis. The degradation of dye was studied by varying different parameters such as laser energy, reaction pH, substrate concentration, catalyst concentration, and in the presence of electron acceptors such as hydrogen peroxide (H2O2), and potassium bromate (KBrO3). The degradation rates were found to be strongly dependent on all the above-mentioned parameters. Our experimental results revealed that the dye degradation process was very fast (within few minutes) under laser irradiation as compared to conventional setups using broad spectral lamps (hours or days) and this laser-induced photocatalytic degradation method could be an effective means to eliminate the pollutants present in liquid phase. The experience gained through this study could be beneficial for treatment of waste water contaminated with organic dyes and other organic pollutants.

Villoglandular adenocarcinoma of the cervix: clarity is needed on the histological definition for this difficult diagnosis.

BACKGROUND: Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. CASES: We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. CONCLUSION: The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data.

Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa.

We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.

A novel naphthanol glycoside from Terminalia arjuna with antioxidant and nitric oxide inhibitory activities.

A novel naphthanol glycoside, arjunaphthanoloside (1), was isolated from the stem bark of Terminalia arjuna and its structure was established as 2,3,6,7,8,9-hexahydroxynaphthalene-2-O-alpha-L(-)-rhamnoside by means of spectroscopic and chemical methods. Compound 1 showed potent antioxidant activity and inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages.

Retreatment of patients with intracranial gliomas by external beam radiotherapy and cytotoxic chemotherapy.

Twenty-one patients with recurrent intracranial gliomas were retreated by external beam radiotherapy between 1987 and 1995. Twenty patients received cytotoxic chemotherapy involving CCNU as part of their retreatment. Only five of the 21 patients had received chemotherapy in combination with the initial external beam radiotherapy (RT) prior to recurrence. The different histological groups were analysed and the patients divided into two groups; group I (Grade I and II gliomas) and group II (Grade III, IV and glioblastoma). The overall median survival for all patients was 59 months, with a median survival of 22 months after recurrence. For group I and group II patients, the median survival was 26 months and 13 months after recurrence respectively. It was concluded that some highly selected patients with intracranial gliomas can be retreated safely by carefully planned external beam RT given to a relatively low dose in order to palliate neurological dysfunction and the symptoms of raised intracranial pressure, and to reduce steroid dependency. The results strongly suggest that recovery does occur after initial RT. Retreatment may possibly improve survival in a small proportion of patients. Further studies, including randomized trial designs, quality of life assessment, and neurological symptoms indices, would be required to determine the quantitative benefit of any such treatment policy. The objectives of this study were to determine whether patients received any benefit, such as symptom relief and the allowance of steroid withdrawal, after retreatment, and whether long term survival could be achieved.

Variable expression of the interleukin-2 receptor alpha chain and MYC genes in lymphocytes from renal cell carcinoma patients treated with interleukin-2.

We have studied the expression of the interleukin-2 receptor alpha chain, c-MYC and L-MYC genes in lymphocytes obtained from four renal cell carcinoma patients undergoing an interleukin-2 clinical trial. Two of these patients exhibited stable disease after the interleukin-2 therapy and two exhibited progressive disease. Analysis of mRNA levels by dot blot hybridization indicated that changes in the expression of both the interleukin-2 receptor alpha chain and c-MYC genes were erratic and varied widely between patients. L-MYC expression was not observed in any sample. There appeared to be little correlation between the changes in gene expression and parameters such as thymidine incorporation, the proportion of CD25 positive cells present or cytotoxic activity. The situation in vivo therefore appears to be more complex than would be predicted from in vitro studies.

Treatment of malignant melanoma and renal cell carcinoma with recombinant human interleukin-2: analysis of cytokine levels in sera and culture supernatants.

In this study we evaluated the clinical response of 12 patients with malignant melanoma and renal cell carcinoma (RCC) following administration of recombinant human interleukin-2 (rhIL-2) by continuous infusion. Serum samples taken before, during and following sequential courses of IL-2 were assayed for the presence of tumour necrosis factor alpha (TNF-alpha) IL-1 alpha, IL-6 and interferon gamma (IFN-gamma) and the presence or changes in these cytokines were examined with respect to clinical response data: our results did not show any direct correlation between the parameters measured and clinical outcome. In addition, peripheral blood mononuclear cells (PBMC) derived from 3 RCC patients were cultured in a serum-free environment and the resulting supernatants assayed for the production of these cytokines and compared to the corresponding serum levels. During one or more courses of treatment only 1 patient, who had metastatic bone disease, demonstrated detectable serum TNF-alpha; serum IL-6 levels were elevated in a proportion of all patients studied and a sustained IL-6 response occurred in a patient who had complete disease remission; IL-1 alpha was detected in the serum of 3 RCC patients; IFN-gamma could not be detected in any serum sample tested. Cytokine levels in sera and supernatants derived from 3 RCC patients were compared but no correlation was found: TNF-alpha and IL-6 were shown to be present at much higher concentrations in supernatants when compared to sera whereas the levels of IL-1 alpha were almost undetectable. This lack of correlation is probably due to the presence of "interfering" proteins in sera which either depress or enhance the ability to detect cytokines in sera using enzyme immunoassays.

Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2.

The immunological and haematological effects of continuous infusion of recombinant human interleukin-2 (rhIL-2) in 6 patients with metastatic melanoma and 6 with disseminated renal cell carcinoma are reported. In patients with malignant melanoma dacarbazine was given before IL-2; in renal cell carcinoma IL-2 alone was given. In malignant melanoma, 1 complete (CR) and 1 partial response (PR) were seen; 2 patients had stable disease (SD) and 2 progressive disease (PD). In renal cell carcinoma 4 patients had SD and 2 PD. Toxicity of IL-2 therapy was minimal. All patients showed increased cytotoxicity, that was not major histocompatibility complex restricted, towards target cells sensitive and insensitive to natural killer cells. These activities varied between individual patients and were less marked in cases of renal cell carcinoma. Cellular proliferative responses increased in all patients, being consistently higher following the first course of therapy, as did HLA-DR, CD16 and CD25 activation marker expression. Hypersegmentation of neutrophils and eosinophilia were commonly observed, and in renal cell carcinoma these changes were accompanied by abnormal lymphocyte morphology.