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61.
Sechi M Angotzi G Dallocchio R Dessì A Carta F Sannia L Mariani A Fiori S Sanchez T Movsessian L Plasencia C Neamati N 《Antiviral chemistry & chemotherapy》2004,15(2):67-81
In a search for new HIV-1 integrase (IN) inhibitors, we synthesized and evaluated the biological activity of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and a series of its derivatives. These compounds were designed as conformationally constrained analogues of the acrylate moiety of caffeic acid phenethyl ester (CAPE). DHICA, an intermediate in the biosynthesis of melanins, was prepared as a monomeric unit by a novel synthetic route. In order to perform coherent SAR studies, two series of DHICA amides were synthesized. First, to validate the utility of a previously identified three-point pharmacophore based on CAPE in inhibitor design, we prepared a series of benzyl- or phenylethylamine substituted derivatives lacking and containing hydroxyl groups. Second, dimers of DHICA containing various aminoalkylamine linkers were also prepared with a goal to increase potency. All compounds were tested against purified IN and the C65S mutant in enzyme-based assays. They were also tested for cytotoxicity in an ovarian carcinoma cell line and antiviral activity in HIV-1-infected CEM cells. Seven compounds inhibited catalytic activities of purified IN with IC50 values below 10 microM. Further computational docking studies were performed to determine the title compounds' mode of interaction with the IN active site. The residues K156, K159 and D64 were the most important for potency against purified IN. 相似文献
62.
63.
Sonal Choudhary Mohamed L. Elsaie Angel Leiva Keyvan Nouri 《Lasers in medical science》2010,25(5):619-627
Tattoos have existed and have been used as an expression of art by man for ages—and so have the techniques to remove them.
Lasers based on the principle of selective photothermolysis are now being used to remove black as well as colorful tattoos
with varying successes. The commonly used lasers for tattoo removal are the Q-switched 694-nm ruby laser, the Q-switched 755-nm
alexandrite laser, the 1,064-nm Nd:YAG laser, and the 532-nm Nd:YAG laser. Newer techniques and methods are evolving in tattoo
removal with lasers. Choosing the right laser for the right tattoo color is necessary for a successful outcome. Our review
aims to understand the principles of laser tattoo removal and their applications for different types and colors of tattoos.
The review also highlights the complications that can occur such as dyspigmentation, allergic reactions, epidermal debris,
ink darkening, and so on, in this process and how to prevent them. 相似文献
64.
Sarcocystis cameli was first described in one-humped camels (Camelus dromedarius), and it is the only species which have so far reported in camels. Although more than 150 species of Sarcocystis were described in various animals, only a few data on camel Sarcocystis ultrastructure were published, and this report is the first for molecular information (DNA sequence and RLFP digestion pattern).
The main objective of the present work is to characterize Sarcocystis isolated from camels by electron microscopy and PCR-RFLP methods. Muscle samples were taken from the fresh esophagus, diaphragm,
skeletal muscles, and heart of one-humped camels (C. dromedarius) slaughtered in abattoirs of Tehran and Ghazvin provinces, Iran. The dissection and trypsin digestion techniques were applied
for the detection of the cysts. The infected samples were fixed in glutaraldehyde and/or frozen at −20°C until use for ultrastructural
and molecular studies, respectively. The ultrastructural and molecular studies were carried out contemporaneously. The 18S
rRNA gene of the parasites was amplified by PCR. The PCR products were cloned into a pTZ57R/T and sequenced. In addition,
the PCR products were digested separately with each of the four restriction enzymes for RFLP. Our results indicated that only
microcysts were observed in muscle samples. The microcysts were white, elongated, spindled, and a few spiral-shaped, with
mean size 260 × 75 μm which are identical with S. cameli. The ultrastructure of microcyst wall had many non-branched finger-like protrusions irregularly folded. There was a 600-bp
specific band amplified after PCR with specific primers. The molecular data for camel Sarcocystis is reported for the first time in Iran and the world. 相似文献
65.
Mohamed Benjelloun A. Nouri Y. Ghannam T. Karmouni K. El Khader A. Koutani A. Ibn Attya M. Hachimi 《The African Journal of Urology》2009,15(4):268-277
Objective
To analyze the various epidemiological, clinical, radiological, pathological and therapeutic aspects of renal cancer in our environment.Patients and Methods
For this retrospective study we reviewed the files of all patients hospitalized at our clinic for renal cancer between 1990 and 2007. In total, 125/155 patients were treated surgically, while surgery was avoided in 30 patients with locally advanced tumors or metastases and/or a poor general condition. The following parameters were studied: age, clinical symptoms, radiological findings, the type of intervention, histopathological results and tumor stage according to the TNM classification. On follow-up all patients were subjected to clinical examination, sonography or abdominal CT scan, chest X-ray and laboratory evaluation of creatinine.Results
The study group consisted of 105 male and 50 female patients with a mean age of 60 (range: 18 to 85) years. The mean time elapsed between the occurrence of symptoms and diagnosis was 9 (range: 1–24) months. The main presenting symptom was hematuria seen in 45,2% of the cases. Diagnosis was based on sonography and CT scan in all our patients. On initial diagnosis the mean tumor size was 10 (range 3–20) cm. The left kidney was affected more frequently than the right one (67% vs. 33%). In 95 patients (61,3%) no distant metastases were encountered, while 60 patients had metastases in other organs or lymph-node metastases. Among these, 30 presented in a poor general condition and/or multiple metastases which contraindicated surgical intervention. In the 30 patients subjected to surgery, the locations of the metastases were as follows: lung (5 cases), lymph nodes (15 cases), bones (2 cases) and liver (8 cases). More than 80% of the tumors were clear-cell (conventional) carcinomas. In all patients subjected to surgery, the method of choice was total radical nephrectomy. Mean follow-up was 62 (range: 6–72) months. Thirty patients were lost to follow-up after the intervention. In total, the survival rates at 3 and 5 years were 78.4% and 47.2%, respectively.Conclusion
Renal cancer is not rare. It presents with various symptoms. The treatment of choice consists of radical nephrectomy. The most reliable prognostic factors are the histological stage (TNM) and grade (Fuhrman). In our study, radical nephrectomy yielded an all-over recurrence-free survival rate of more than 85%. 相似文献66.
Y. Elbelkasmi M. Benjelloun A. Nouri T. Karmouni K. Tazi K. Elkhader A. Koutani A. Ibn Attya M. Hachimi 《The African Journal of Urology》2009,15(1):67-71
Radical nephroureterectomy with a bladder cuff remains the treatment of choice of transitional cell carcinoma of the upper urinary tract. Conservative treatment mainly presents an alternative for patients at risk of developing terminal renal insufficiency after nephroureterectomy and may be indicated for localized tumors of low grade and stage requiring regular, relatively non-invasive monitoring. We report the case of a patient who presented with a localized transitional cell carcinoma of the left pelvic ureter, which was managed by conservative treatment yielding successful results after a follow-up of 10 years. Based on this observation and a review of the literature we discuss the various aspects of conservative treatment of localized transitional cell carcinoma of the ureter. 相似文献
67.
Mouna Chelli Bouaziz Mohamed Hedi Meherzi Helmi Jlassi Habib Nouri Skander Chaabane Mohamed Samir Daghfous Slaheddine Karray Mohamed Fethi Ladeb 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2009,19(6):427-432
Adamantinoma of long bones is a malignant primitive bone tumor with epithelial origin, involving the tibia in a great majority
of cases. It is a rare neoplasm with less than 200 cases reported in the world literature. The authors report four cases of
tibial adamantinoma and describe the clinical, imaging and histologic features of this neoplasm with emphasis on preoperative
imaging, surgical treatment and post-operative follow-up. 相似文献
68.
HIV-1 integrase inhibitors: 2005-2006 update 总被引:2,自引:0,他引:2
HIV-1 integrase (IN) catalyzes the integration of proviral DNA into the host genome, an essential step for viral replication. Inhibition of IN catalytic activity provides an attractive strategy for antiretroviral drug design. Currently two IN inhibitors, MK-0518 and GS-9137, are in advanced stages of human clinical trials. The IN inhibitors in clinical evaluation demonstrate excellent antiretroviral efficacy alone or in combination regimens as compared to previously used clinical antiretroviral agents in naive and treatment-experienced HIV-1 infected patients. However, the emergence of viral strains resistant to clinically studied IN inhibitors and the dynamic nature of the HIV-1 genome demand a continued effort toward the discovery of novel inhibitors to keep a therapeutic advantage over the virus. Continued efforts in the field have resulted in the discovery of compounds from diverse chemical classes. In this review, we provide a comprehensive report of all IN inhibitors discovered in the years 2005 and 2006. 相似文献
69.
Brzozowski Z Saczewski F Sławiński J Sanchez T Neamati N 《European journal of medicinal chemistry》2009,44(1):190-196
A series of novel 3-aroyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazines 15-28 as potential HIV-1 integrase (IN) inhibitors have been synthesized by the reduction of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines 1-14 with benzenesulfonyl hydrazide. All the compounds 15-28 inhibited IN mediated strand transfer reaction with IC(50) values ranging from 3 to 30 microM. The 3-(4-bromobenzoyl)-6-chloro-7-methyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazine 17 with the IC(50) values of 4+/-1 and 3+/-1 microM for 3'-processing and strand transfer, respectively, was the most potent. Compound 17 as well its analogues were 5-20-fold less potent in Y99S and H114A mutants, implicating these residues as potential drug-binding site. This is a first report implicating Y99S and H114A of IN core domain in drug-binding interactions. 相似文献
70.
HIV-1 integrase (IN) executes the insertion of proviral DNA into the host cell genome, an essential step in the retroviral life cycle. This is a multi-step process that starts in the cytosol and culminates in the nucleus of the infected cell. It is becoming increasingly clear that IN interacts with a wide range of different host-cell proteins throughout the viral life cycle. These cellular cofactors are exploited for various functions, including nuclear import, DNA target-site selection and virion assembly. The disruption of key interactions between IN and direct cellular cofactors affords a novel therapeutic approach for the design and development of new classes of anti-retroviral agents. Here, we will discuss the rationale behind this emerging and promising therapeutic strategy for HIV drug discovery. Our discussion includes the identified IN cellular cofactors, key research developments in the field and the implications this approach will have on the current HIV treatment regimen. 相似文献