CML

The function of an oscillator is to convert dc energy into RF. Voltage Controlled Oscillator (VCO) is a type of oscillator whose output frequency can be varied by a control voltage. Here the VCO is designed using 0.18µm CMOS-RF technology using current mode logic. The Current mode logic is the fastest logic and is mainly used in Clock and Data Recovery applications. Current mode logic (CML) is a differential logic and provides noise immunity. Using the proposed design the current mode logic VCO operates with a supply voltage of 1.8 V and frequency varies from 2 MHz to 2.5 MHz. Its normalized supply sensitivity is 0.976 and optimum sensitivity is 0.966.

The current trend of burn wound care has shifted to a more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various etiologies. At present, there is no ideal skin substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesized on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialization characteristics due to the presence of a basement membrane. Acellular dermal scaffold are one of the types of biological skin substitutes which has the extracellular matrix (ECM) almost like the normal skin extracellular matrix. For regeneration and healing of deep burn wound, ECM plays a very important role in rapid healing with minimum scar. Although some acellular dermis based products are available in foreign market, their prohibitive high cost prevents the Indian patient population to use it. Hence, this Method was designed to prepare an acellular dermis, indigenously, suitable for clinical application. NaOH method was used to standardize the decellularization method. In our observation, six weeks of decellularization was sufficient to completely decellularize the skin as confirmed by H&E Staining. Also, it was found out to be biocompatible by cell culture assay.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder. Current targeted therapies designed to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein have made a significant breakthrough in the treatment of CML patients. However, CML remains a chronic disease that a patient must manage for life. Although tyrosine kinase inhibitors (TKI) therapy has completely transformed the prognosis of CML, it has made the therapeutic management more complex. The interruption of TKI treatment results in early disease progression because it does not eliminate quiescent CML stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML to achieve a permanent cure, and to allow TKI interruption. This review summarizes recent research done on alternative targeted therapies with a particular focus on some important signaling pathways (such as Alox5, Hedgehog, Wnt/b-catenin, autophagy, and PML) that have the potential to target CML stem cells and potentially provide cure for CML.

INTRODUCTION: We assessed the feasibility of flow cytometry-fluorescent in situ hybridization technique in the detection of translocated mRNA in the cytoplasm of human peripheral blood nucleated cells. It is assumed that this assay can be applied as a diagnostic method in the detection of chromosomal translocation which commonly occurs in hematologic malignancies. METHODS: KCL-22 cell line and white blood cells from 21 CML patients were recruited in the study. Cells were isolated and fixed. After permeabilization, cells were resuspended in hybridization buffer and probes were added to the mixture. Subsequently, cells were washed and analyzed on the flow cytometer instrument. The flow cytometry results were compared with qRT-PCR and fluorescent microscope outcomes. RESULTS: Using the current principle, 97 ± 2.1% of the KCL-22 cells were labeled with b2a2 mRNA-specific probes. In addition, seven patients were recognized positive for t(9;22) b2a2. The percentage of cells containing abovementioned translocation in these patients was varied from 3.26% to 97.8%. There was no false-positive result in negative controls (K562 with BCR-ABL1 b3a2, NB4, and Jurkat cell lines) along with blood samples of normal controls. All the results obtained by flow-FISH were confirmed by qRT-PCR and fluorescent microscope. CONCLUSION: This strategy benefits from appropriate specificity, sensitivity, rapidity, and ability in the determination of malignant cell percentage. Therefore, it can improve traditional time-consuming and labor-intensive FISH method.

The function of an oscillator is to convert dc energy into RF. Voltage Controlled Oscillator (VCO) is a type of oscillator whose output frequency can be varied by a control voltage. Here the VCO is designed using 0.18µm CMOS-RF technology using current mode logic. The Current mode logic is the fastest logic and is mainly used in Clock and Data Recovery applications. Current mode logic (CML) is a differential logic and provides noise immunity. Using the proposed design the current mode logic VCO operates with a supply voltage of 1.8 V and frequency varies from 2 MHz to 2.5 MHz. Its normalized supply sensitivity is 0.976 and optimum sensitivity is 0.966.

Apresentação do Africa.cont, em 2008: o booklet desaparecido.
O anteprojecto do arquitecto nigeriano-britânico David Adjaye. O complexo edificado incluiria o Palacete Pombal, na Rua das Janelas Verdes, nº 37, e as 3 construções conhecidas como Tercenas de Santos ou do Marquês, que vão em planos descendentes até à 24 de Julho.
Era para a ser Centro de Cultura Contemporânea Africana na proposta aprovada no dia 3 de Dez de 2008 pela Câmara de Lisboa, e passou a ser referido mais informalmente apenas como África.Cont.
Africa.Cont definia-se como um "centro multidisciplinar e interdisciplinar para o conhecimento de África e das suas diásporas nos seus desenvolvimentos contemporâneos", e apontava como um dos seus objectivos (o 2º objectivo) "constituir acervos de arte contemporânea africana que passarão a ser património inalienável da Fundação".

Amaç: Tirozin kinaza özgü bir inhibitör olan STI571 KML kemoterapisinde kullanılır. Diğer kemoterapötik ajanlara benzer şekilde, bazı hastalarda ilaç direnci ve intoksikasyon sebebiyle sınırlı bir etkinliğe sahiptir. Bu yüzden, çoğu kanser hastası kemoterapötik ajanın etkinliğini artırmak için günlük ek gıdalar ve bitkisel ekstraktları kullanır. Kakaonun bir metaboliti olan teobromin prooksidan etkilere sahiptir ve hücreiçi sinyal yolaklarını düzenler. Çalışmamızın amacı birlikte ve birarada kullanıldığında STI571 ve teobrominin K562 hücreleri üzerinde potansiyel apoptotik etkilerini göstermektir.
Yöntem: STI571 ve teobrominin inhibitör konsantrasyonları MTT metoduyla belirlendi. Her iki ajan da hücrelere 48 saat süre ile tek başına ve birlikte olacak şekilde uygulandı. Kaspaz aktiviteleri kolorimetrik olarak belirlendi. Apoptoz ve nekroz akridin turuncusu/etidyum bromür boyaması ile değerlendirildi. p< 0,05 istatiksel olarak anlamlı kabul edildi.
Bulgular: Kaspaz aktiviteleri her iki ajan tek başlarına uygulandığında artış gösterdi. Teobromin STI571’in kaspaz aktivitesini kaspaz tipine ve süreye bağımlı olarak artırdı (p<0,05). Apoptotik hücre oranları iki ajan bir arada kullanıldığında da uygulama süresine bağlı olarak arttı (p<0,05). Teobromin nekrotik hücre oranlarını azalttı.
Sonuç: Bu in vitro çalışma ile hücre içi sinyal yolaklarındaki etkisi henüz tam olarak anlaşılamamış olan teobrominin STI571 tarafından yürütülen apoptotik cevapta kaspazlar üzerinden etkili olduğu gösterilmiştir. Bu verilerin daha sonra yapılacak çalışmalara ışık tutacağını düşünüyoruz.

Anahtar kelimeler: STI571, teobromin, kaspaz, apoptozis, KML


Abstract
Objective: STI571, a selective tyrosine kinase inhibitor is used in CML chemotherapy. It has limited effects in some cases due to drug resistance and intoxication as other chemotherapeutic agents. Thus, many cancer patients use dietary supplements and herbal extracts for increasing the effectiveness of chemotherapeutic agents. Theobromine, a metabolite of cacao has prooxidant effects and regulates intercellular signaling pathways. The aim of the study is to determine the potential apoptotic effects of STI571 and theobromine on K562 cells, when used alone and in combination.
Methods: Inhibitory concentrations of STI571 and theobromine were determined by MTT method. Both agents were applied to the cells at 48 h time period alone and in combination. Caspase activities were assessed colorimetrically. Apoptosis and necrosis were evaluated by using acridine orange/ethidium bromide staining. p<0.05 was considered as statistically significant.
Results: Caspase activities increased when both agents administrated alone. Theobromine increased effects of STI571 on caspase activities in time and type dependent manner (p<0.05). Apoptotic cell rates also increased when two agents applied in combination (p<0.05) in time dependent manner. Theobromine also reduced necrotic cell rates.
Conclusion:
Although there are limited data about the intracellular effects of theobromine, we showed that theobromine has effects on the caspase pathway related apoptotic response carried out by STI571. We believe that this in vitro study will shed light for further researches.
Keywords: STI571, theobromine, caspase, apoptosis, CML

Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. These conditions may lead to formation of advanced glycation end-products (AGEs). In this study we investigated in 88 COPD patients and 55 control subjects (80% exsmokers) the association of the plasma protein-bound AGEs N ε -(carboxymethyl)lysine (CML), pentosidine, N ε -(carboxyethyl)lysine (CEL) and AGE accumulation in skin by skin auto fluorescence (AFR) with lung function. Plasma CML (COPD: 61.6 ± 15.6, never smokers: 80.7 ± 19.8 , ex-smokers: 82.9±19.3 nmol/mmol lysine) was decreased and CEL (COPD: 39.1±10.9, never smokers: 30.4±5.0, ex-smokers : 27.7±6.4 nmol/mmol lysine), and AFR (COPD: