Mechanism of Escherichia coli Resistance to Pyrrhocoricin

Due to their lack of toxicity to mammalian cells and good serum stability, proline-rich antimicrobial peptides (PR-AMPs) have been proposed as promising candidates for the treatment of infections caused by antimicrobial-resistant bacterial pathogens. It has been hypothesized that these peptides act on multiple targets within bacterial cells, and therefore the likelihood of the emergence of resistance was considered to be low. Here, we show that spontaneous Escherichia coli mutants resistant to pyrrhocoricin arise at a frequency of approximately 6 × 10⁻⁷. Multiple independently derived mutants all contained a deletion in a nonessential gene that encodes the putative peptide uptake permease SbmA. Sensitivity could be restored to the mutants by complementation with an intact copy of the sbmA gene. These findings question the viability of the development of insect PR-AMPs as antimicrobials.     

Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. METHODS: Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. RESULTS: Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. CONCLUSIONS: IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.     

Self-assembled pearl-necklace patterned upconverting nanocrystals with highly efficient blue and ultraviolet emission: femtosecond laser based upconversion properties

This work reports new findings on the formation of a pearl-necklace pattern in self-assembled upconverting nanocrystals (UCN-PNs) which exhibit strong upconversion emission under an NIR excitation source of a femtosecond laser (Fs-laser). Each nano-necklace consists of several upconversion nanoparticles (UCNPs) having a size ca. 10 ± 1 nm. UCN-PNs are arranged in a self-organized manner to form necklace type chains with an average length of 140 nm of a single row of nanoparticles. Furthermore, UCN-PNs are comprised of UCNPs with an average interparticle separation of ca. 4 nm in each of the nanonecklace chains. Interestingly, these UCN-PNs exhibit high energy upconversion especially in the UV region on interaction with a 140 Fs-laser pulse duration at 80 MHz repetition rate and intense blue emission at 450 nm on interaction with a 900 nm excitation source is obtained. The preparation of self-assembled UCNPs is easy and they are very stable for a longer period of time. The emission (fluorescence/luminescence) intensity is very high which can make them unique in innumerable industrial and bio-applications such as for disease diagnosis and therapeutic applications by targeting the infected cells with enhanced efficiency.

Self-assembled pearl necklace patterned-upconverting nanoparticles and their femtosecond laser based upconversion properties.     

Expression of nerve growth factor during the development of nervous system in early chick embryo

In the chick gastrula, nerve growth factor (NGF) is localized to the endoblast mesoblast presumptive head ectoderm but not in the presumptive neuroectoblast. During early morphogenesis the dorsal body ectoderm presumptive neural crest cells exhibit strong NGF positive cell surface reaction. NGF appears to be a marker of cells participating in morphogenetic movements but not early neural differentiation. NGF is localized where neural folds fuse and cells die allowing detachment of the neural tube from head ectoderm as well as in dead cells in the neurocoele. NGF reactivity in cells lining the evaginated extremities of the optic vesicle the floor of the neural tube the splanchnopleure heart primordia the inner outer surfaces of somites is suggestive of the role of NGF in primitive organ shaping.     

Radioimmunotargeting of human rhabdomyosarcoma using monoclonal antibody 8H9

Although metastatic rhabdomyosarcoma (RMS) is chemotherapy and radiotherapy responsive, few patients are cured. 8H9, a murine IgG(1) monoclonal antibody, recognizes a unique cell surface tumor antigen broadly distributed on neuroectodermal, epithelial, and mesenchymal tumors, including RMS. We now report on the in vitro characterization of radiolabeled 8H9 and its in vivo immunotargeting potential in mice with subcutaneous human RMS. Saturation-binding studies carried out to determine (125)I-8H9 affinity to the RMS cell line HTB82 demonstrated that (125)I-8H9 had a K(d) of 10.3nM with an estimated 115,000 binding sites on every HTB82 cell. (125)I-8H9 was retained on the cell surface without significant internalization. Biodistribution of (125)I-8H9 was studied in athymic mice bearing HTB82 xenografts. Following intravenous injection of 4.44MBq of (125)I-8H9, selective tumor uptake was evident 4 to 172 hours after injection. Average tumor uptake was 7.0 +/- 1.8, 11.5 +/- 3.9, 15.1 +/- 3.7, and 5.4 +/- 1.2% injected dose per gram at 4, 24, 48, and 172 hours, respectively. Mean tumor: tissue ratios were maximal at 172 hours (for lung, 4, kidney, 6, liver, 7, spleen, 11, femur, 14, muscle, 18, and brain, 48). Established RMS xenografts treated with a single injection of 18.5 MBq (131)I-8H9 were significantly suppressed compared to controls. Radiolabeled 8H9 effectively targeted RMS xenografts and may have a potential clinical role in radioimmunotherapy.     

Epidemiological study of eclampsia in a referral teaching hospital

The present study is a retrospective analysis of 864 eclampsia patients managed at RG Kar Medical College and Hospital, Kolkata during the period January 1999 to December 2001. The incidence of eclampsia was seen in about 2.27% cases. Majority (51.97%) of eclampsia patients were between 20 and 29 years though 41.43% were below 20 years of age. They were mostly primigravida (88.19%) and Hindus (69.1%). About 44.56% were antepartum eclampsia patients. All the patients were treated with magnesium sulphate. Caesarean section rate is quite high (46.18%) in this present study. Maternal case fatality rate was 7.29%. Still birth rate was 9.92% with an early neonatal death rate of 14.15% resulting in a perinatal mortality of 24.07%. Ignorance regarding antenatal check-up, lack of transport and lack of early communication with tertiary hospital play an important role for high incidence of eclampsia in our developing country.     

L-[1-(13)C] phenylalanine breath test for monitoring hepatic function after living donor liver transplant surgery

Although metabolic response after partial hepatectomy has been well studied in animal models, there are few studies examining restoration of metabolic capacity after right hepatectomy in humans. The L-[1-(13)C]-phenylalanine breath test (PBT) is a simple non-invasive diagnostic tool which allows measurement of liver functional reserve. We investigated the PBT for monitoring hepatic function in living liver donors by measuring the metabolism of L-[1-(13)C]-phenylalanine ((13)C-Phe). We used (13)C-Phe administered orally and iv to adult living liver donor patients and measured exhaled (13)CO(2) to determine the extent of metabolic impairment and time course of its return. Patients given oral (13)C-Phe had approximately 70-90% reduction in (13)CO(2) production compared with baseline 2-3 days after surgery. Patients given iv (13)C-Phe had only 40-50% reduction in (13)CO(2) production and recovered their baseline (13)C-Phe metabolism much sooner than their oral (13)C-Phe metabolic capacity (P < 0.05). In some cases oral (13)C-Phe did not recover to baseline for as long as 56 days after surgery. Patients recovering (13)C-Phe metabolism had significantly higher (13)CO(2) recovery 60 min after ingestion by day 4 (0.97 versus 3.06, P = 0.033) and day 7 (1.50 versus 5.02, P = 0.031). We conclude that orally administered amino acids may not be well absorbed and/or metabolized in some subjects for weeks after partial hepatectomy whereas intravenously delivered substrates are much better oxidized by the regenerating liver. These findings may be due to impaired gut motility due to trauma to the gastrointestinal tract or portal venous flow that reduces delivery of oral agents after liver surgery. In early recovery phase for living liver donor patients, the iv PBT would be a better predictor of functional hepatic reserve.     

Treatments against Polymorphosal discrepancies in Glioblastoma Multiforme

Glioblastoma (GB) are aggressive tumors that obstruct normal brain function. While the skull cannot expand in response to cancer growth, the growing pressure in the brain is generally the first sign. It can produce more frequent headaches, unexplained nausea or vomiting, blurred peripheral vision, double vision, a loss of feeling or movement in an arm or leg, and difficulty speaking and concentrating; all depend on the tumor’s location. GB can also cause vascular thrombi, damaging endothelial cells and leading to red blood cell leakage. Latest studies have revealed the role of single nucleotide polymorphisms (SNPs) in developing and spreading cancers such as GB and breast cancer. Many discovered SNPs are associated with GB, particularly in great abundance in the promoter region, creating polygenetic vulnerability to glioma. This study aims to compile a list of some of the most frequent and significant SNPs implicated with GB formation and proliferation.