Structure–antimicrobial activity of some natural isocoumarins and their analogues

Three naturally occurring isocoumarins (paepalantine, paepalantine 9-O-beta-D-glucopyranoside and paepalantine 9-O-beta-D-allopyranosyl(1 --> 6) glucopyranoside) and two semi-synthetic analogues, 9,10-acylated compound and 9-OH-10-methylated compound, structurally similar to paepalantine, were evaluated for antimicrobial activity using a spectrophotometric microdilution technique. The paepalantine was active against S. aureus, S. epidermidis, and E. faecalis while the other four compounds proved ineffective against all microorganisms tested at concentrations of 500 microg/ml. Variations in phenolic substitution at OH-9 and/or OH-10 in the paepalantine molecule resulted in compounds without antimicrobial activity. A combination of structural features, two phenolic groups as cathecolic system, forms an oxygenated system arrangement that may reflect the potentially antimicrobial properties of paepalantine.     

Arg-Gly-Asp (RGD) sequence conjugated in a synthetic copolymer bearing a sugar moiety for improved culture of parenchymal cells (hepatocytes)

A copolymer, including a Gly-Arg-Gly-Asp-Ser (GRGDS) sequence and sugar moieties, was synthesized for the culturing of parenchymal cells (hepatocytes). Hepatocyte cells attached to poly[N-p-vinylbenzyl-d-maltonamide-co-6-(p-vinylbenzamido)-hexanoic acid-GRGDS] [poly(VMA-co-VBRGD)]-coated dishes grew approximately 60% better than on other polymer-coated surface for 12 h. Also, about 80% greater albumin secretion (0.38 pg ml^–1) and about 70% greater urea synthesis (0.495 pg ml^–1) from hepatocytes were produced in this matrix as compared with unstimulated cells. The behaviour of hepatocytes on poly(VMA-co-VBGRGDS)-coated dishes was not distinct from those attached to a collagen. The conjugation of the adhesion molecules of the RGD peptide in the poly(VMA-co-VBGRGDS) copolymer therefore specifically interacts with integrin families on the hepatocyte cell membrane.     

Socially isolated? How parents and neighbourhood adults influence youth behaviour in disadvantaged communities

William Julius Wilson’s model of adult joblessness, community disorganization and their effects on youth problem behaviour de-emphasizes the range in children’s outcomes across socially disorganized communities, and says little about the factors that influence this variation. It also does not address the processes by which family structure and relationships affect the well-being of African-American and poor youth. My work is part of a larger research agenda that has begun to address these issues by focusing on the differential rates of sexual activity among youth living in disadvantaged environments, and developing models to explain this variation. This work suggests that units of socially cohesive, stable adults exist among the social networks of successful children and families in poor neighbourhoods. It also points to the existence and functioning of alternative two-parent family structures and offers hypotheses for how family environment interacts with neighbourhood context to influence youth behaviour.     

Comparison of dose distribution in IMRT and RapidArc technique in prostate radiotherapy

AimThe aim was to provide a dosimetric comparison between IMRT and RapidArc treatment plans with RPI index with simultaneous comparison of the treatment delivery time.BackgroundIMRT and RapidArc provide highly conformal dose distribution with good sparing of normal tissues. However, a complex spatial dosimetry of IMRT and RapidArc plans hampers the evaluation and comparison between plans calculated for the two modalities. RPI was used in this paper for treatment plan comparisons. The duration of the therapeutic session in RapidArc is reported to be shorter in comparison to therapeutic time of the other dynamic techniques. For this reasons, total treatment delivery time in both techniques was compared and discussed.Materials and methods15 patients with prostate carcinoma were randomly selected for the analysis. Two competitive treatment plans using respectively the IMRT and RapidArc techniques were computed for each patient in Eclipse planning system v. 8.6.15. RPIwin^® application was used for RPI calculations for each treatment plan.Additionally, total treatment time was compared between IMRT and RapidArc plans. Total treatment time was a sum of monitor units (MU) for each treated field.ResultsThe mean values of the RPI indices were insignificantly higher for IMRT plans in comparison to rotational therapy. Comparison of the mean numbers of monitor units confirmed that the use of rotational technique instead of conventional static field IMRT can significantly reduce the treatment time.ConclusionAnalysis presented in this paper, demonstrated that RapidArc can compete with the IMRT technique in the field of treatment plan dosimetry reducing the time required for dose delivery.     

Synthesis and biological evaluation of glucose conjugated phthalocyanine as a second-generation photosensitizer

Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can’t be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-infrared (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles.     

The Detection of Hamster Connexins: A Comparison of Expression Profiles with Wild-Type Mouse and the Cancer-Prone Min Mouse

The open reading frames of 17 connexins from Syrian hamster (using tissues) and 16 connexins from the Chinese hamster cell line V79, were fully (Cx30, Cx31, Cx37, Cx43 and Cx45) or partially sequenced. We have also detected, and partially sequenced, seven rat connexins that previously were unavailable. The expression of connexin genes was examined in some hamster organs and cultured hamster cells, and compared with wild-type mouse and the cancer-prone Min mouse. Although the expression patterns were similar for most organs and connexins in hamster and mouse, there were also some prominent differences (Cx29 and 30.3 in testis; Cx31.1 and 32 in eye; Cx46 in brain, kidney and testis; Cx47 in kidney). This suggests that some connexins have species-specific expression profiles. In contrast, there were minimal differences in expression profiles between wild type and Min mice. Species-specific expression profiles should be considered in attempts to make animal models of human connexin-associated diseases.     

The art of cobbling a running pump—Will human embryonic stem cells mend broken hearts?

The heart is one of the least regenerative organs in the body, and highly vulnerable to the increasing incidence of cardiovascular diseases in an aging world population. Cell-based approaches aimed at cardiac repair have recently caused great public excitement. But clinical trials of patients’ own skeletal myoblasts or bone marrow cells for transplantation have been disappointing. Human embryonic stem cells (hESCs) form bona fide cardiomyocytes in vitro which are readily generated in mass culture and are being tested in animal models of heart damage. The early results, while encouraging, underscore that much remains to be done. This review focuses on the many challenges that remain before hESCs-mediated repair of the human heart becomes a reality.     

Hatchery selection promotes boldness in newly hatched brown trout (Salmo trutta): implications for dominance

By using newly hatched (approximately 2 weeks old) brown trout(Salmo trutta) from six families of wild and six families ofsea-ranched origin (seventh generation), we tested the hypothesesthat (1) the hatchery environment selects for increased boldness,and (2) boldness predicts dominance status. Sea-ranched troutspend their first 2 years in the hatchery before being releasedinto the wild at the onset of seaward migration. Trout werepresented with a novel object (tack) and with food (brine shrimp),and their responses were measured and scored in terms of boldness.Siblings with increasing difference in boldness were then pairedin dyadic contests. Fish of sea-ranged origin were on averagebolder than were fish of wild origin, and bolder individualswere more likely to become dominant regardless of origin. Boldnesswas not related to RNA levels, indicating that bold behaviorwas not a consequence of higher metabolism or growth rate. Neitherwas size a predictor of bold behavior or the outcome of dyadiccontests. These results are consistent with studies on olderlife stages showing increased boldness toward predators in hatchery-selectedfish, which suggests that behavioral consequences of hatcheryselection are manifested very early in life. The concordancebetween boldness and dominance may suggest that these behaviorsare linked in a risk prone-aggressive phenotype, which may bepromoted by hatchery selection. However, we also found significantvariation in behavioral and growth-related traits among families,suggesting that heritable variation has not been exhausted bysea-ranching procedures.     

Upstream Regulators and Downstream Effectors of NADPH Oxidases as Novel Therapeutic Targets for Diabetic Kidney Disease

Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-β. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.     

Synthesis,photophysical properties and biological evaluation of β-alkylaminoporphyrin for photodynamic therapy

A series of β-alkylaminoporphyrins conjugated with different amines at β position (D1–D3) or with electron-donating and electron-withdrawing substituents at phenyl position (D4–D6) were synthesized. Their photophysical and photochemical properties, intracellular localization, photocytotoxicities in vitro and vivo were also investigated. All target compounds exhibited no cytotoxicities in the dark and excellent photocytotoxicities against HeLa cells. Among them, D6 showed the highest phototoxicity and the lowest dark toxicity, which was more phototoxic than Hematoporphyrin monomethyl ether (HMME). In addition, D6 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing HeLa tumor. Therefore, D6 is a powerful and promising antitumor photosensitizer for photodynamic therapy.