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31.
32.
Mujahid Hussain Bukhari Matloob Ahmad Tanvir Hussain Syed Umar Naveed Ahmad 《Medicinal chemistry research》2013,22(11):5248-5254
A novel series of eleven 4-(4-(1H-imidazol-1-yl)phenyl)-6-arylpyrimidin-2-amines has been prepared from synthesized 3-[4-(1H-imidazol-1-yl) phenyl]prop-2-en-1-ones and evaluated for phosphodiesterase (PDE) inhibition and antimicrobial activities. N-arylation of imidazole with 4-fluorobenzaldehyde using hexadecyltrimethylammonium bromide as catalyst gave 4-(1H-imidazol-1-yl) benzaldehyde which on treatment with substituted acetophenones yielded corresponding chalcones (1a–1k). Each chalcone on further reaction with guanidine hydrochloride resulted in title compounds (2a–2k). Pyrimidines thus synthesized were subjected to biological studies. Some compounds showed marked activities in PDE inhibition and anti-bacterial and anti-fungal bioassays. 相似文献
33.
Syed Umar Farooq Rizvi Hamid Latif Siddiqui Muhammad Nisar Ahmad Matloob Ahmad Mujahid Hussain Bukhari 《Medicinal chemistry research》2012,21(7):1322-1333
A series of twenty-two new pyrazoline derivatives was prepared from quinoline-based chalcones which in turn were synthesized by condensing formylquinolines with diverse acetylthiophenes. The titled compounds were characterized by spectroscopic techniques (NMR, IR and MS) and elemental analysis. All the compounds were screened for antileishmanial activities. Compounds 1e, 1f, 2a, 2c, 2d, 2g, 2k, and 4a were found potentially active antileishmanial agents. Bioassay results show that the type and positions of the substituents seem to be critical for their antileishmanial activities. 相似文献
34.
Shashi P. Singh Sravanthi Gundavarapu Kevin R. Smith Hitendra S. Chand Ali Imran Saeed Neerad C. Mishra Julie Hutt Edward G. Barrett Matloob Husain Kevin S. Harrod Raymond J. Langley Mohan L. Sopori 《Environmental health perspectives》2013,121(8):957-964
Background: Cigarette smoke (CS) exposure during gestation may increase the risk of bronchopulmonary dysplasia (BPD)—a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angiogenesis, and diminished surfactant protein production and may increase the risk of chronic obstructive pulmonary disease.Objective: We investigated whether gestational exposure to secondhand CS (SS) induced BPD and sought to ascertain the role of nicotinic acetylcholine receptors (nAChRs) in this response.Methods: We exposed BALB/c and C57BL/6 mice to filtered air (control) or SS throughout the gestation period or postnatally up to 10 weeks. Lungs were examined at 7 days, 10 weeks, and 8 months after birth.Results: Gestational but not postnatal exposure to SS caused a typical BPD-like condition: suppressed angiogenesis [decreased vascular endothelial growth factor (VEGF), VEGF receptor, and CD34/CD31 (hematopoietic progenitor cell marker/endothelial cell marker)], irreversible hypoalveolarization, and significantly decreased levels of Clara cells, Clara cell secretory protein, and surfactant proteins B and C, without affecting airway ciliated cells. Importantly, concomitant exposure to SS and the nAChR antagonist mecamylamine during gestation blocked the development of BPD.Conclusions: Gestational exposure to SS irreversibly disrupts lung development leading to a BPD-like condition with hypoalveolarization, decreased angiogenesis, and diminished lung secretory function. Nicotinic receptors are critical in the induction of gestational SS–induced BPD, and the use of nAChR antagonists during pregnancy may block CS-induced BPD. 相似文献
35.
BACKGROUND: Breath holding spells (BHS) are apparently frightening events occurring in otherwise healthy children. Generally, no medical treatment is recommended and parental reassurance is believed to be enough, however, severe BHS can be very stressful for the parents and a pharmacological agent may be desired in some of these children. OBJECTIVE: In this prospective study aim was to determine the usefulness of piracetam as prophylactic treatment for severe BHS. METHODS: Children were recruited from Neurology Clinic in Children's Hospital, Islamabad between January 2002 to December 2004. Diagnosis of BHS was based on characteristic history and normal physical examination. Piracetam was prescribed to those children who were diagnosed as severe BHS in a dose ranging from 50-100 mg/kg/day. Iron supplements were added if hemoglobin was less than 10 gm%. Patients were seen at 2-4 weeks interval and follow-up was continued until 3 months after the cessation of drug therapy. RESULTS: Fifty-two children were enrolled in the study, 34 boys and 18 girls. Ages ranged from 4 weeks to 5 years with mean age of 17 months. In 81% of children, spells disappeared completely and in 9% frequency was reduced to less than one per month and of much lesser intensity. Prophylaxis was given for 3-6 months (mean 5) duration. CONCLUSIONS: Piracetam is an effective prophylactic treatment for severe BHS. 相似文献
36.
Dixon-Salazar TJ Silhavy JL Udpa N Schroth J Bielas S Schaffer AE Olvera J Bafna V Zaki MS Abdel-Salam GH Mansour LA Selim L Abdel-Hadi S Marzouki N Ben-Omran T Al-Saana NA Sonmez FM Celep F Azam M Hill KJ Collazo A Fenstermaker AG Novarino G Akizu N Garimella KV Sougnez C Russ C Gabriel SB Gleeson JG 《Science translational medicine》2012,4(138):138ra78
The translation of "next-generation" sequencing directly to the clinic is still being assessed but has the potential for genetic diseases to reduce costs, advance accuracy, and point to unsuspected yet treatable conditions. To study its capability in the clinic, we performed whole-exome sequencing in 118 probands with a diagnosis of a pediatric-onset neurodevelopmental disease in which most known causes had been excluded. Twenty-two genes not previously identified as disease-causing were identified in this study (19% of cohort), further establishing exome sequencing as a useful tool for gene discovery. New genes identified included EXOC8 in Joubert syndrome and GFM2 in a patient with microcephaly, simplified gyral pattern, and insulin-dependent diabetes. Exome sequencing uncovered 10 probands (8% of cohort) with mutations in genes known to cause a disease different from the initial diagnosis. Upon further medical evaluation, these mutations were found to account for each proband's disease, leading to a change in diagnosis, some of which led to changes in patient management. Our data provide proof of principle that genomic strategies are useful in clarifying diagnosis in a proportion of patients with neurodevelopmental disorders. 相似文献
37.
Husain M Weisberg AS Moss B 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(51):19506-19511
In thin sections of cells infected with vaccinia virus or other poxviruses, the viral membrane is first discerned as a crescent or circle lacking obvious continuity with a cellular organelle, presenting an appearance of de novo membrane biogenesis. This notion, which many consider heretical, is nevertheless consistent with the absence of a signature of endoplasmic reticulum (ER) trafficking, such as signal peptide cleavage or glycosylation, in any of the numerous viral membrane proteins. The purpose of this study was to determine whether an operative pathway exists between the ER and the immature virion membrane. We showed that the highly conserved A9 viral membrane protein was inserted into the ER of uninfected cells with the same topology as in viral membranes. Next, we found that replacement of the nonessential cytoplasmic tail of A9 with one containing COPII-binding sites reduced incorporation of the modified A9 into viral membranes and led to its accumulation in the Golgi apparatus, implying that A9 was inserted into the ER and then diverted from its natural path. Most importantly, we demonstrated cleavage of a heterologous signal peptide fused to the N-terminal region of A9 and localized the truncated protein in immature and mature virions. Additionally, immunoelectron micrographs showed A9 in tubules containing protein disulfide isomerase, an ER lumenal protein, near immature viral membranes. The present data provide strong evidence for an operative pathway from ER domains within the virus factory to the viral membrane. 相似文献
38.
Andrea Salonia Giuseppe Zanni Andrea Gallina Alberto Briganti Antonino Saccà Nazareno Suardi Rayan Matloob Luigi F. Da Pozzo Roberto Bertini Renzo Colombo Patrizio Rigatti Francesco Montorsi 《The journal of sexual medicine》2009,6(12):3347-3355
IntroductionInvestigating preoperative sexual function of patients with prostate cancer (PCa) and their partners is needed for realistic functional outcome analyses after radical prostatectomy (RP).AimTo assess pre‐RP sexual health issues of PCa patients and their partners in a stable heterosexual relationship.MethodsData were analyzed from 3,282 consecutive patients who underwent RP over a three‐period survey. During Period 1, on admission to the hospital the day prior to surgery, 1,360 patients were asked to complete the International Index of Erectile Function (IIEF). During Period 2, 1,171 patients were asked to complete the preoperative IIEF; similarly, patients' partners were invited to complete the Female Sexual Function Index (FSFI). Lastly, during Period 3, only candidates for RP were asked to fill in the IIEF.Main Outcome MeasuresTo assess the rate of patients who completed the questionnaire during the three‐period survey. To detail the proportion of patients' partners who filled in the questionnaire, along with the partners' reasons for non‐adherence to the proposed investigation during Period 2.ResultsA small rate of men completed the IIEF during Period 1 (583 in 1,360 [42.9%]), Period 2 (290 in 1,171 [24.8%]), and Period 3 (261 in 751 [34.8%]) (χ2 trend: 13.06; P = 0.0003). In this context, a significantly lower proportion of patients completed the questionnaire during Period 2, as compared with both Period 1 (χ2: 95.13; P = 0.0001) and Period 3 (χ2: 21.87; P < 0.0001). Only 82 in 1,171 (7.0%) partners completed the FSFI over Period 2. Moreover, only 6 in 82 (7.3%) of women provided complete data.ConclusionsThe investigation of sexual health issues of both partners prior to RP is largely unsuccessful. In this context, the prevalence of incomplete data collection is high, and these results demonstrate that contemporaneously investigating the sexual health issues of both partners significantly increases the prevalence of incomplete data collection. Salonia A, Zanni G, Gallina A, Briganti A, Saccà A, Suardi N, Matloob R, Da Pozzo LF, Bertini R, Colombo R, Rigatti P, and Montorsi F. Unsuccessful investigation of preoperative sexual health issues in the prostate cancer “couple”: results of a real‐life psychometric survey at a major tertiary academic center. 相似文献
39.
Syed Umar Farooq Rizvi Matloob Ahmad Mujahid Hussain Bukhari Catherine Montero Payel Chatterjee Mervi Detorio Raymond F. Schinazi 《Medicinal chemistry research》2014,23(1):402-407
Biological studies of two series of 38 quinolinyl chalcones (4a–s and 5a–s) were investigated for their in vitro anti-HIV-1 and cytotoxic activities. Out of 38 compounds, seventeen compounds were observed as good anti-HIV-1 agents with EC50 values less than 20 μM. Compounds 4a, 4l, 4o, 5e, 5h, 5l, 5o, and 5r displayed potent anti-HIV-1 activity with EC50 values less than 5 μM. Among these, compound 5h emerged as the best anti-HIV-1 agent (EC50 = 1.1 μM). Compounds 4d, 4n, 4q, 4r, 4s, 5n, and 5r showed no toxicity in human lymphocytes. Bioassay results show that the type(s) and position(s) of the substituents seem to be critical for their cytotoxic and anti-HIV-1 activities. These results could be useful in the invention of new anti-HIV agents through structural modification. 相似文献