Del(1)(q23) in a patient with Hutchinson‐Gilford progeria

A 9‐year‐old patient with the classical clinical picture of Hutchinson‐Gilford progeria (HGP) is described. The karyotype shows a 46,XY,del(1)(q23) constitution. Our findings suggest that the interval 1q23 may play a roll in the etiology of HGP. A perturbation in glycosylation in connective tissue has been demonstrated in patients with this condition. This abnormality may be due to a defect in the UDP‐galactose:β‐N‐acetylglucosamina‐β‐1,4‐galactosyltransferase 3 (B4GALT3) gene that has been mapped in the interval 1q21‐23. The cytogenetical analyses of this patient suggest that the B4GALT3 gene could be involved in the pathogenesis of HGP. © 2002 Wiley‐Liss, Inc.     

Antibacterial prenylated acylphloroglucinols from the fern Elaphoglossum yungense

Seven new prenylated acylphloroglucinols, yungensins A-G, were isolated from the diethyl ether extract of the scaly rhizomes and roots of an Argentine collection of the fern Elaphoglossum yungense. All the compounds contained a geranyl group attached to the filicinic acid-type residue. The diethyl ether extract and yungensins A-F displayed antibacterial effects against Staphylococcus aureus and Pseudomonas aeruginosa with MICs ranging from 10 to 200 μg/mL. All tested acylphloroglucinols, except for yungensin D, caused bacteriolysis of S. aureus at MBC or higher doses (50-200 μg/mL). At 10 μg/mL, the ether extract as well as yungensins A, B, and D-F altered the biofilm production in both microoganisms.     

Leishmanicidal and trypanocidal activity of extracts and secondary metabolites from basidiomycetes

Seventeen extracts and seven secondary metabolites isolated from basidiomycetes were tested in medium culture against promastigote forms of Leishmania spp. and bloodstream forms of Trypanosoma cruzi. Extracts from the culture filtrate or mycelium were generally inactive against the parasites except the Zucoagaricus genus mycelium extract which reduced by 47% the number of bloodstream forms. Striatin A, striatin B and podoscyphic acid exhibited in vitro activity at 10, 5 and 100 μg/mL, respectively. One compound showed activity against bloodstream forms of T. cruzi, the sesquiterpenoid naematolin, lysing the parasites by 79%. BALB/c mice infected with L. amazonensis were treated 3 weeks post-infection with striatin A and striatin B by subcutaneous route for 15 days at 10 mg/kg daily. The reference drug, N-methylglucamine antimonate, administered by subcutaneous injections at 28 mg Sbv/kg/day for 15 days reduced the parasite burden by 71.2% (p <0.05). Subcutaneous administration of straitin A at 10 mg/kg produced a weak decrease of the parasite burdens in the footpad by 17.6%. The treatment with striatin B had no effect and showed higher toxicity than striatin A. © 1997 John Wiley & Sons, Ltd.     

Compositional Analysis of Extracellular Aggregates in the Eyes of Patients With Exfoliation Syndrome and Exfoliation Glaucoma

PurposeExfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals.MethodsPieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography–mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy.ResultsA small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-β–binding protein-2 and latent transforming growth factor-β–binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-β superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA.ConclusionsThis analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.     

Distinctive accumulation patterns of Cd(II), Cu(II), and Cr(VI) in tissue of the South American teleost, pejerrey (Odontesthes bonariensis)

The time- and concentration-dependent accumulation patterns of three environmentally relevant metals, with different chemical and biological properties, were comparatively evaluated in tissue of South American fish, pejerrey (Odontesthes bonariensis). Six-month-old juvenile pejerrey were exposed to 1, 5, or 10 microgl(-1) of Cd(2+); 10, 50, or 100 microgl(-1) of Cu(2+); or 100, 500, or 1000 microgl(-1) of Cr(6+) during 16 days. Tested concentrations ranged from those that caused no significant accumulation to those that induced growth reduction or even mortality (Cd and Cu). Concentration-dependent accumulation of Cd and Cr presented similar patterns, characterized by a linear and exponential relationship in the gill and liver, respectively, with a greater slope at longer exposure times. Differently, essential Cu showed a linear relationship in both tissues, and no slope increase was observed in the gill. The gill time-dependent accumulation pattern of Cd exhibited relatively long times to half-saturation (t(1/2(1))=36.6 days) and high-saturation values (S((1))=205.4 nmolg(-1)). The opposite pattern was observed for Cu (t(1/2(100))=0.6 days; S((100))=24.4 nmolg(-1)), while Cr showed an intermediate position (t(1/2(1000))=2.8 days; S((1000))=50.2 nmolg(-1)). In the liver, times to half saturation for the three metals were as follows: Cd=4.7 days; Cu=2.5 days; Cr=1.6 days. Conversely, different saturation concentrations were observed among metals, Cu (S((100))=102) presenting the highest values, Cd (S((10))=4.4) the lowest, and Cr presenting an intermediate position (S((1000))=24.7). Bioconcentration of non-essential Cd was high in the gill (2000-fold) and low in the liver (50-fold). On the other hand, the essential element Cu was poorly retained by the gill (15-fold) and accumulated mainly in the liver (50-fold). Differently, Cr was quickly and evenly accumulated by both organs, but barely bioconcentrating (2.5- and 1.5-fold levels as compared to the original in the gill and liver, respectively). The ratio of gill/liver concentration in exposed fish clearly differed from that of non-exposed fish, and was characteristic for each metal (Cd>1; Cu<1; Cr<9), representing a potential tool to assess exposure. The accumulation patterns of studied metals in the tissue of pejerrey corresponded more with those reported for sensitive than for tolerant fish species. Distinctive tissue accumulation patterns in relation to growth reduction and non-acute lethality suggests different target tissues for sub-chronic effects, and would partially explain differences in the relative toxicity of these metals.     

Port Pocket Infections: Hydrogel Reduces Time to Healing and Clinic Visits Compared with Iodoform Gauze

Pocket infections are an occasional complication of totally implanted central venous catheters. The purpose of this study was to compare the safety, efficacy, and efficiency of the use of hydrogel after port removal vs the conventional method of packed iodoform gauze. In a cohort of 31 patients, the hydrogel group (n = 13) healed significantly faster than the group treated with the conventional method (15.5 vs 26.8 d; P = .009) and required fewer scheduled clinic visits (1.2 vs 10.8; P < .001). There were no differences in complications. This study suggests that hydrogel effectively promotes healing of port pocket infections, with advantages over the established technique.     

Exposure to light-at-night increases the growth of DMBA-induced mammary adenocarcinomas in rats

In order to assess whether light exposure at night influences the growth of mammary tumors, as well as the role of melatonin in this process, female rats bearing DMBA-induced mammary adenocarcinomas were exposed to different lighting environments. Animals exposed to light-at-night, especially those under a constant dim light during the darkness phase, showed: (a) significantly higher rates of tumor growth as well as lower survival than controls, (b) higher concentration of serum estradiol, and (c) lower nocturnal excretion of 6-sulfatoxymelatonin, without there being differences between nocturnal and diurnal levels. These results suggest that circadian and endocrine disruption induced by light pollution, could induce the growth of mammary tumors.