Novel association of multiple gastrointestinal anomalies in a single patient: Can Sonic Hedgehog explain it?

The occurrence of four gastrointestinal (GIT) anomalies in a single patient is extremely rare. Only one report of four GIT anomalies in a child has been published in the English literature. The current report presents a child with four anomalies and discusses the molecular mechanisms which control the development of the gastrointestinal tract.     

Immune Mediators of Protective and Pathogenic Immune Responses in Patients with Mild and Fatal Human Monocytotropic Ehrlichiosis

ABSTRACT: BACKGROUND: Ehrlichia chaffeensis is a bacterial pathogen that causes fatal human monocytic ehrlichiosis (HME) that mimic toxic shock-like syndrome. Murine studies indicate that over activation of cellular immunity followed by immune suppression plays a central role in mediating tissue injury and organ failure during fatal HME. However, there are no human studies that examine the correlates of resistance or susceptibility to severe and fatal HME. RESULTS: In this study, we compared the immune responses in two patients with mild/non fatal and severe/fatal HME who had marked lymphopenia, thrombocytopenia and elevated liver enzymes. The levels of different immunological factors in the blood of those patients were examined and compared to healthy controls. Our data showed that fatal HME is associated with defective production of Th1 cytokines such as ( IFNgamma and IL-2), increased anti-inflammatory (IL-10 and IL-13) and pro-inflammatory (TNF-alpha, IL-1alpha, IL-1beta, and IL-6) cytokines, increased levels of macrophages, T cells, and NK cells chemokines such as MCP-1, MIP-1alpha, MIP-1beta but not RANTES and IP-10, increased levels of neutrophils chemokine and growth factor (IL-8 and G-CSF), and elevated expression of tumor necrosis factor receptor (TNFR), and toll like receptors 2 and 4 compared to patients with non fatal HME and healthy controls. CONCLUSIONS: Fatal Ehrlichia-induced toxic shock is associated with defective Th1 responses, possible immune suppression mediated by IL-10. In addition, marked leukopenia observed in patients with fatal disease could be attributed to enhanced apoptosis of leukocytes and/or elevated chemokine production that could promote migration of immune cells to sites of infection causing tissue injury.     

Improved Plasmodium berghei lines for conditional mutagenesis

Conditional mutagenesis is a powerful tool for genetic analysis in Plasmodium berghei. It allows the study of proteins that function both during the parasite's pre-erythocytic and erythrocytic development. Currently available parasite lines used for conditional mutagenesis were constructed in the NK65 strain, and express a DNA recombinase under the control of pre-erythrocytic stage-specific promoters. However, the integration of the recombinase in these lines is unstable leading to inconsistent excision of the target gene. We describe improved lines of P. berghei with stably integrated DNA recombinase that allow efficient, stage-specific excision of target genes in the widely used ANKA strain.     

Rapid and accurate determination of tissue optical properties using least-squares support vector machines

Diffuse reflectance spectroscopy (DRS) has been extensively applied for the characterization of biological tissue, especially for dysplasia and cancer detection, by determination of the tissue optical properties. A major challenge in performing routine clinical diagnosis lies in the extraction of the relevant parameters, especially at high absorption levels typically observed in cancerous tissue. Here, we present a new least-squares support vector machine (LS-SVM) based regression algorithm for rapid and accurate determination of the absorption and scattering properties. Using physical tissue models, we demonstrate that the proposed method can be implemented more than two orders of magnitude faster than the state-of-the-art approaches while providing better prediction accuracy. Our results show that the proposed regression method has great potential for clinical applications including in tissue scanners for cancer margin assessment, where rapid quantification of optical properties is critical to the performance.     

Comparative evaluation of propolis and triantibiotic mixture as an intracanal medicament against Enterococcus faecalis

Introduction

The aim of this study was to evaluate and compare the antimicrobial activity of calcium hydroxide, triantibiotic mixture (TAM), and an ethanol extract of propolis as intracanal medicaments on Enterococcus faecalis-infected root canals.

Methods

One hundred twenty extracted intact human permanent incisors were decoronated, and chemomechanical preparation of the root canal was performed. After sterilization of the samples, they were inoculated with pure culture of E. faecalis and incubated. After incubation, colony-forming units were recorded before medication. Then, samples were divided randomly into five groups (n = 24). Each group was then exposed to various intracanal medicaments, namely calcium hydroxide (group 1), TAM (group 2), propolis (group 3), ethanol (group 4), and saline as the control group (group V). The antibacterial effectiveness of the different intracanal medicament was recorded by determining the percentage reduction in colony counts (%RCC) at the end of days 1, 2, and 7. The data were statistically analyzed using one-way analysis of variance and Tukey Honestly Significant Difference (HSD) post hoc test.

Results

The %RCC was highest for propolis showing 100% reduction on day 2 followed by TAM showing 82.5%, 92.2%, and 98.4% of reduction on days 1, 2, and 3, respectively. Calcium hydroxide showed a gradual increase in antibacterial activity with a maximum of 59.4% on day 7.

Conclusions

Propolis was more effective than TAM against E. faecalis at a 2-day time period, and both were equally effective at 7 days.     

Semi-synthetic modification of nimbolide to 6-homodesacetylnimbin and 6-desacetylnimbin and their cytotoxic studies

A new C-seco tetranortriterpenoid named as 6-homodesacetylnimbin 2, has been synthesised for the first time through semi-synthetic modification of nimbolide 1, a potent molecule with anticancer activity. Attempts were made to transesterify the -COOMe moiety in nimbolide using titanium (IV) isopropoxide and ethanol so as to obtain a molecule with -COOEt moiety. However, a novel product was envisaged during the course of the reaction, which was identified as 6-homodesacetylnimbin, a higher homologue of 6-desacetylnimbin 3 through spectroscopic and crystallographic methods. Also, 6-desacetylnimbin has been synthesised through acid hydrolysis of nimbolide. The compounds were screened for their cytotoxic properties through brine shrimp lethality bioassay method using Artemia salina.