Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation Against <Emphasis Type="Italic">L. major</Emphasis> and <Emphasis Type="Italic">L. tropica</Emphasis>

Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti-leishmanial drug treatment strategy. Besides producing new, active anti-leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising anti-leishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P?<?0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach.     

Length–weight relationships of five commercial fish species from the Strait of Hormuz in the Persian Gulf

Length‐weight relationships are described for five fish species from the coast of the Hormuz Strait in the Persian Gulf, Iran. Specimens were collected between August 2010 and July 2011 using shrimp beam trawls, gill nets and intertidal fishing weirs. Relationships for three of the species had no previous data in the international science global databank on fishes: www.FishBase.org . A new maximum length was recorded for Acanthopagrus latus.     

Higher tyrosine protein kinase activity in resting lymphocytes than in proliferating normal or leukaemic blood cells

We have studied tyrosine phosphorylation in particulate fractions from 11 leukaemic cell lines by using as substrate either a synthetic tyrosine containing peptide or the endogenous proteins. The results were compared with those obtained using similar fractions from normal lymphocytes and bone marrow cells. Particulate fractions from all the leukaemic cell lines and normal bone marrow cells exhibited lower levels of tyrosine protein kinase activity compared to normal lymphocytes. When the phosphorylation of endogenous substrates was assayed, proteins were phosphorylated on tyrosine residues (rather than serine or threonine residues) to a larger extent in normal lymphocytes than in leukaemic cell lines. Separation of labelled endogenous substrates on sodium dodecyl sulfate-polyacrylamide gels showed a number of phosphorylated alkali-resistant bands in the range 14-175kd in the lymphoid cell lines; normal lymphocytes exhibited a smaller number of strongly phosphorylated bands. Normal lymphocytes from different individuals showed reproducible patterns of phosphorylated substrates. Normal bone marrow cells and myeloid leukaemia lines showed weak, if any, phosphorylation. Among the leukaemic cell lines no particular pattern of phosphorylated substrates common to cells of similar phenotype could be detected. We suggest that the level of overall tyrosine protein kinase activity in these fractions reflects their position in the cell cycle rather than their normal or malignant status.     

The Impact of a Diabetes Local Enhanced Service on Quality Outcome Framework Diabetes Outcomes

Background

The rising challenge of diabetes requires novel service delivery approaches. In the UK, Local Enhanced Services (LES) have been commissioned for diabetes. Health professionals from general practices (GPs) who signed up to LES were given additional training (and a monetary incentive) to improve management of patients with diabetes. All practices in the PCT were invited to the LES initiative, which ensured avoiding selection bias. The aim of the study was to examine the impact of LES in terms of diabetes Quality Outcome Framework (QOF) indicators: DM23(glycaemia), DM17(lipid) and DM12(blood pressure; BP).

Methods

QOF diabetes indicators were examined using data from 76 general practices for 2009–2010 in a large primary care trust area in Birmingham, UK. Data were extracted from Quality Management Analysis System. The primary outcome was a difference in achievement of QOF indicators between LES and NLES practices. A secondary outcome was the difference between LES and non-LES practices for hospital first and follow-up appointments.

Results

We did not find any difference for DM12(BP) and DM17(lipid) outcomes between LES and NLES practices. However, LES practices were more likely to achieve the DM23(glycaemia) outcome (estimated odds 1.459;95% CI:1.378-1.544; P=0.0001). The probability of achieving satisfactory level of DM23(glycaemia) increased by almost 10% when GPs belonged to LES groups compared with GPs in NLES group. LES practices were less likely to refer patients to secondary care.

Conclusion

Overall, LES practices performed better in the achievement of DM23(glycaemia) and also referred fewer patients to hospital, thereby meeting their objectives. This suggests that the LES approach is beneficial and needs to be further explored in order to ascertain whether the impact exerted was due to LES.     

Secondary Infertility: A Neglected Aspect of Buerger’s Disease

Background:During the gathering of demographic data for the biobank on Buerger’s Disease (BD), we found that, after the clinical manifestation of BD, the patients usually became infertile, and the age of their last child was compatible with the time of disease diagnosis. The aim of this study was to evaluate the underlying cause of secondary infertility in BD patients.Methods:Anti-sperm antibodies (ASA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the sera of 39 male BD patients were measured and compared with 39 age-matched Caucasian male controls.Results:Six patients declared that they suffered from impotency. The ASA level was positive in 25.6% of the patients and 2.4% of the controls (p= 0.003, CC= 6.96). The mean levels of testosterone in the patients and controls were 393.12±32.9 ng/dl and 354.37±30.9 ng/dl, respectively. The mean levels of LH in the patients and controls were 0.88±0.12 mIU/r and 0.85±0.1 mIU/r, respectively. The mean levels of FSH in the patients and controls were 4.1± 0.35 mIU/r and 3.56±0.33 mIU/r, respectively. No significant difference in the serum levels of testosterone, LH, or FSH was found between the patients and controls (p> 0.05). The spermograms of three ASA-negative patients demonstrated impaired sperm motility.DiscussionAnti-sperm antibodies, disturbed genital circulation, autonomic dysfunction and sperm motility may be responsible for secondary infertility in Buerger’s Disease.Key Words: Anti-sperm antibody, Buerger’s Disease, Infertility, Thromboangiitis Obliterans     

Temporal expression profile of CXC chemokines in serum of patients with spinal cord injury

Chemokines, a subclass of cytokine superfamily have both pro-inflammatory and migratory role and serve as chemoattractant of immune cells during the inflammatory responses ensuing spinal cord injury (SCI). The chemokines, especially CXCL-1, CXCL-9, CXCL-10 and CXCL-12 contribute significant part in the inflammatory secondary damage of SCI. Inhibiting chemokine’s activity and thereby the secondary damage cascades has been suggested as a chemokine-targeted therapeutic approach to SCI. To optimize the inhibition of secondary injury through targeted chemokine therapy, accurate knowledge about the temporal profile of these cytokines following SCI is required. Hence, the present study was planned to determine the serum levels of CXCL-1, CXCL-9, CXCL-10 and CXCL-12 at 3–6 h, 7 and 28 days and 3 m after SCI in male and female SCI patients (n = 78) and compare with age- and sex-matched patients with non-spinal cord injuries (NSCI, n = 70) and healthy volunteers (n = 100). ANOVA with Tukey post hoc analysis was used to determine the differences between the groups. The data from the present study show that the serum level of CXCL-1, CXCL-9 and CXCL-10 peaked on day 7 post-SCI and then declined to the control level. In contrast, significantly elevated level of CXCL-12 persisted for 28 days post SCI. In addition, post-SCI expression of CXCL-12 was found to be sex-dependent. Male SCI patients expressed significantly higher CXCL-12 when compared to control and SCI female. We did not observe any change in chemokines level of NSCI. Further, the age of the patients did not influence chemokines expression after SCI. These observations along with SCI-induced CSF-chemokine level should contribute to the identification of selective and temporal chemokine targeted therapy after SCI.