Mitochondrial DNA sequence diversity in three ethnic populations from the South-west Iran: a preliminary study

To investigate the genetic structure of human populations in the South-west region of Iran, mitochondrial first hypervariable DNA sequences were obtained from 50 individuals representing three different ethnic groups from Khuzestan Province. Studied groups were Shushtari Persians and Chahar Lang Bakhtiyaries from Indo-European-speaking populations and Bani Torof Arabs from Semitic-speaking linguistic families. Genetic analysis of mtDNA data showed high similarity of Chahar Lang Bakhtiyaries with other Iranian Indo-European-speaking populations while Shushtaries and Bani Torofs had a closer affinity with Semitic-speaking groups rather than to other Iranian populations. The relationship of Chahar Lang Bakhtiyaries and Bani Torof Arabs with their neighbor populations can be explained by linguistic and geographic proximity. Whereas, the greater similarity of Shushtari Persians with West Asian Arabs is probably according to high gene flow between them. This article represents a preliminary study of three major ethnic groups of South-west Iran which investigates the potential genetic substructure of the region.     

Lymphocyte subsets show different response patterns to in vivo bound natalizumab--a flow cytometric study on patients with multiple sclerosis

Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS) and interferes with immune cell migration into the central nervous system by blocking the α(4) subunit of very-late activation antigen-4 (VLA-4). Although well tolerated and very effective, some patients still suffer from relapses in spite of natalizumab therapy or from unwanted side effects like progressive multifocal leukoencephalopathy (PML). In search of a routine-qualified biomarker on the effectiveness of natalizumab therapy we applied flow cytometry and analyzed natalizumab binding to α(4) and α(4) integrin surface levels on T-cells, B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a significant and sustained increase of lymphocyte-bound natalizumab (p<0.001) which was paralleled by a significant decrease in detectability of the α(4) integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced natalizumab accumulations on T and B cells at single measurements in all patients who reported clinical disease activity (n?=?4). The natalizumab binding capacity of in vitro saturated lymphocytes collected during therapy was strongly diminished compared to treatment-naive cells indicating a therapy-induced reduction of α(4). Summing up, this pilot study shows that flow cytometry is a useful method to monitor natalizumab binding to lymphocytes from RRMS patients under therapy. Investigating natalizumab binding provides an opportunity to evaluate the molecular level of effectiveness of natalizumab therapy in individual patients. In combination with natalizumab saturation experiments, it possibly even provides a means of studying the feasability of patient-tailored infusion intervals. A routine-qualified biomarker on the basis of individual natalizumab saturation on lymphocyte subsets might be an effective tool to improve treatment safety.     

Neurotensin and CRH Interactions Augment Human Mast Cell Activation

Stress affects immunity, but the mechanism is not known. Neurotensin (NT) and corticotropin-releasing hormone (CRH) are secreted under stress in various tissues, and have immunomodulatory actions. We had previously shown that NT augments the ability of CRH to increase mast cell-dependent skin vascular permeability in rodents. Here we show that NT triggered human mast cell degranulation and significantly augmented CRH-induced vascular endothelial growth factor (VEGF) release. Investigation of various signaling molecules indicated that only NF-κB activation was involved. These effects were blocked by pretreatment with the NTR antagonist SR48692. NT induced expression of CRH receptor-1 (CRHR-1), as shown by Western blot and FACS analysis. Interestingly, CRH also induced NTR gene and protein expression. These results indicate unique interactions among NT, CRH, and mast cells that may contribute to auto-immune and inflammatory diseases that worsen with stress.     

Investigation of the Effects of Hydroalcoholic Solutions on Textural and Rheological Properties of Various Controlled Release Grades of Hypromellose

Hypromellose (hydroxypropyl methylcellulose, HPMC) matrices are widely used in the formulation of sustained release dosage forms. The integrity and performance of an HPMC matrix formulation depends on rapid hydration and gel formation upon ingestion. Due to the recent alert issued by the Food and Drug Administration regarding the potential negative influence of alcoholic beverages on extended release (ER) formulations, several researchers have evaluated the potential influence of hydroalcoholic media on drug release from ER dosage forms. It has been reported that HPMC matrix formulations do not show “dose dumping” in hydroalcoholic media. The purpose of this study was a fundamental investigation on the effect of hydroalcoholic solutions (0–40% v/v ethanol) on textural and rheological properties of different viscosity grades of neat HPMC, as the functional ingredient within a hydrophilic matrix. In general, hydroalcoholic solutions had little effect on gel formation and mechanical properties of hydrated compacts, while the rheological behavior of HPMC showed dependency on the ethanol content of such solutions.     

1–3 β-D-glucan: From Diagnosis to Prognosis

There are increasing numbers of patients at risk for invasive fungal infections (IFI). The early diagnosis of IFI’s is limited by the lack of sensitivity and delayed turn-around time of routine cultures. Delays in diagnosis are associated with poor outcomes, especially with immunocompromised hosts and patients within the intensive care unit (ICU). Over the last decade, fungal biomarkers such as galactomannan and 1,3-β-D-glucan (BDG) have been increasingly utilized for the early and accurate diagnosis of these infections. This review will evaluate the recent clinical data on the BDG assay, focusing on its ability to assist in the diagnosis of invasive candidiasis in the ICU, and also whether BDG kinetics can predict the prognosis of the patient. Similarly, this review will evaluate BDG in invasive Aspergillus and Pneumocystis jiroveci diagnosis and prognosis, as well as the current limitations of the assay.     

The effects of cultivation depth,areal density,and nutrient level on lipid accumulation of <Emphasis Type="Italic">Scenedesmus acutus</Emphasis> in outdoor raceway ponds

Lipid accumulation is critical in the production of biodiesel from microalgae. However, little work has been done on the assessment of lipid accumulation during nitrogen stress in large research-scale outdoor raceways during different seasons; most values for lipid accumulation are assumptions based on work completed in laboratory settings or outdoor photobioreactors. This study focused on the use of raceway ponds operated in batch cultivation mode with an area of 30.37 m² to determine the impacts of nitrate-nitrogen concentration and cultivation depth on the ability of Scenedesmus acutus strain LB 0414 to accumulate lipids. A concentration of less than 60 mg N-NO₃ ^??L^?1 was required for removal of nitrogen in the cultivation medium within 8 days to stimulate lipid accumulation and increase lipid productivity. When nitrate concentrations were increased to prevent nitrogen depletion, lipid productivity decreased, which demonstrates that stressing is needed to induce lipid accumulation for increased lipid productivity. Additionally, decreasing cultivation depth below 9 cm, compared to raceways operated at a depth of 20–24 cm, increased lipid productivity by 62 % in December 2014 and 38 % in February 2015. More desirable environmental conditions, mainly increased sunlight and temperature, in February, increased biodiesel productivity for all raceways and account for the decrease in productivity differences. This research highlights increased lipid productivity found by reducing cultivation depth and nitrogen concentrations in outdoor raceways and provides insight into the optimal conditions for large-scale biodiesel production.