Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives

Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.     

Using polymerase chain reaction to human papillomavirus in oral and pharyngolaryngeal carcinomas

Purpose: Increasingly, evidence has shown that human papillomavirus (HPV) plays a role in the induction of certain carcinomas. The presence of HPV sequences in 56 previously untreated oral and pharyngolaryngeal carcinomas was examined by the polymerase chain reaction (PCR).Materials and Methods: After DNA extraction, samples underwent 40 replication cycles with specific oligonucleotide primers corresponding to sequences from the E6 open-reading frame of HPV-6b, HPV-16, and HPV-18. To determine the E6 genomic integration, positive samples were processed with specific primers for the corresponding HPV L1 genes. Genomic HPV DNA cloned into PBR 322 was used as positive control.Results: HPV E6 DNA of the 6b and 16 types was detected in 14 patients (25%). The L1 gene was not present.Conclusion: Detected HPV E6 DNA might be integrated into the cell genome in the positive cases as indicated by the absence of the L1 gene-coding for the viral capside. Histological and clinical parameters, such as tumor location, degree of differentiation, stage, recurrence, and survival rates, were unrelated to the presence of HPV.     

Screening for sediment toxicity in the Rio Santiago basin: A baseline study

Toxicity testing of sediment samples from the Rio Santiago and its main tributaries was performed using a battery of tests that included the ECHA dipstick biocide monitor, the MetPad test, the lettuce seed germination and the root elongation test, the nematode test, spot plate test, and the SOS Chromotest. Assessment was carried out on organic extracts, pore water, and direct sediment. Results of bioassays showed toxicity sources from tributaries and canals flowing into the river and areas being degraded by insults from industrial spills. © by John Wiley & Sons, Inc.     

Recycling and EH domain proteins at the synapse

In neurons, a network of endocytic proteins accomplishes highly regulated processes such as synaptic vesicle cycling and the timely internalization of intracellular signaling molecules. In this review, we discuss recent advances on molecular networks created through interactions between proteins bearing the Eps15 homology (EH) domain and partner proteins containing the Asn–Pro–Phe (NPF) motif, which participate in important aspects of neuronal function as the synaptic vesicle cycle, the internalization of nerve growth factor (NGF), the determination of neuronal cell fate, the development of synapses and the trafficking of postsynaptic receptors. We discuss novel functional findings on the role of intersectin and synaptojanin and then we focus on the features of an emerging family of EH domain proteins termed EHDs (EH domain proteins), which are important for endocytic recycling of membrane proteins.     

Molecular biology in prostate cancer

Summary Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includesex vivo corrective therapy, suicide, and antisense therapy.     

Inter-observer agreement in interpreting chest X-rays on children with acute lower respiratory tract infections and concurrent wheezing.

CONTEXT AND OBJECTIVE: Many children with acute lower respiratory tract infections (ALRI) present to the emergency ward with concurrent wheezing. A chest x-ray is often requested to rule out pneumonia. We assessed inter-observer agreement in interpreting x-rays on such children. DESIGNS AND SETTING: Prospective consecutive case study at Instituto de Salud del Ni?o, Lima, Peru. METHODS: Chest x-rays were obtained from eligible children younger than two years old with ALRI and concurrent wheezing who were seen in the emergency ward of a nationwide pediatric referral hospital. The x-rays were read independently by three different pediatric residents who were aware only that the children had a respiratory infection. All the children had received inhaled beta-adrenergic agonists before undergoing chest x-rays. Lobar and complicated pneumonia cases were excluded from the study. RESULTS: Two hundred x-rays were read. The overall kappa index was 0.2. The highest individual kappa values for specific x-ray findings ranged from 0.26 to 0.34 for rib horizontalization and from 0.14 to 0.31 for alveolar infiltrate. Inter-observer variation was intermediate for alveolar infiltrate (kappa 0.14 to 0.21) and for air bronchogram (kappa 0.13 to 0.23). Reinforcement of the bronchovascular network (kappa 0.10 to 0.16) and air trapping (kappa 0.05 to 0.20) had the lowest agreement. CONCLUSIONS: There was poor inter-observer agreement for chest x-ray interpretation on children with ALRI and concurrent wheezing seen at the emergency ward. This may preclude reliable diagnosing of pneumonia in settings where residents make management decisions regarding sick children. The effects of training on inter-observer variation need further studies.