The effects of saffron supplementation on the measures of renal function indicators: a systematic review and meta-analysis

International Urology and Nephrology - Saffron (Crocus sativus L.) has been proposed as a potential agent to improve renal function in animal studies. But, due to insufficient evidence in human...     

In Vitro Inhibitory Effect of Berberis vulgaris (Berberidaceae) and Its Main Component,Berberine against Different Leishmania Species

Background

Leishmaniasis has been identified as a major public health problem in tropical and sub-tropical countries. The present study was aimed to investigate antileishmanial effects of various extracts of Berberis vulgaris also its active compoenent, berberine against Leishmania tropica and L. infantum species on in vitro experiments.

Methods

In this study in vitro antileishmanial activity of various extracts of B. vulgaris also its active compoenent, berberine against promastigote and amastigote stages of L. tropica and L. infantum was evaluated, using MTT assay and in a macrophage model, respectively. Furthermore, infectivity rate and cytotoxicity effects of B. vulgaris and berberine in murine macrophage cells were investigated.

Results

The findings of optical density (OD) and IC₅₀ indicated that B. vulgaris particulary berberine significantly (P<0.05) inhibited the growth rate of promastigote stage of L.tropica and L.infantum in comparison to meglumine antimoniate (MA). In addition, B. vulgaris and berberine significantly (P<0.05) decreased the mean number of amastigotes in each macrophage as compared with positive control. In the evaluation of cytotoxicity effects, it could be observed that berberine as compared with B. vulgaris exhibited more cytotoxicity against murine macrophages. Results also showed that when parasites were pre-incubated with B. vulgaris their ability to infect murine macrophages was significantly decreased.

Conclusion

B.vulgaris particularly berberine exhibited potent in vitro leishmanicidal effects against L. tropica and L.infantum. Further works are required to evaluate the antileishmanial effects of B.vulgaris on Leishmania species using clinical settings.     

PU.1 as an essential activator for the expression of gp91phox gene in human peripheral neutrophils, monocytes, and B lymphocytes

We have reported a deficiency of a 91-kDa glycoprotein component of the phagocyte NADPH oxidase (gp91^phox) in neutrophils, monocytes, and B lymphocytes of a patient with X chromosome-linked chronic granulomatous disease. Sequence analysis of his gp91^phox gene revealed a single-base mutation (C → T) at position −53. Electrophoresis mobility-shift assays showed that both PU.1 and hematopoietic-associated factor 1 (HAF-1) bound to the inverted PU.1 consensus sequence centered at position −53 of the gp91^phox promoter, and the mutation at position −53 strongly inhibited the binding of both factors. It was also indicated that a mutation at position −50 strongly inhibited PU.1 binding but hardly inhibited HAF-1 binding, and a mutation at position −56 had an opposite binding specificity for these factors. In transient expression assay using HEL cells, which express PU.1 and HAF-1, the mutations at positions −53 and −50 significantly reduced the gp91^phox promoter activity; however, the mutation at position −56 did not affect the promoter activity. In transient cotransfection study, PU.1 dramatically activated the gp91^phox promoter in Jurkat T cells, which originally contained HAF-1 but not PU.1. In addition, the single-base mutation (C → T) at position −52 that was identified in a patient with chronic granulomatous disease inhibited the binding of PU.1 to the promoter. We therefore conclude that PU.1 is an essential activator for the expression of gp91^phox gene in human neutrophils, monocytes, and B lymphocytes.     

Molecular characterization of antibody specificities against myelin/oligodendrocyte glycoprotein in autoimmune demyelination

Myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for myelin-destructive Abs in autoimmune central nervous system demyelinating disorders. Little is known about the molecular and structural basis of these pathogenic Ab responses. Here, we have characterized anti-MOG Ab specificities in the marmoset model of experimental allergic encephalomyelitis, by means of a combinatorial IgG-Fab library. We found that a diverse population of Ig genes encodes for auto-Abs that exclusively recognize conformation-dependent antigenic targets on MOG. These antigenic domains correspond to exposed epitopes in vivo, as the Fab fragments recognize native MOG in situ in marmoset brain tissue. The Ab fragments described here represent Ab specificities that are common constituents of the humoral immune repertoire against MOG in outbred populations, as demonstrated by their ability to displace native anti-MOG Abs present in sera from MOG-immune marmosets and patients with multiple sclerosis. Furthermore, neuropathological analysis and characterization of Ab epitope specificities in animals immunized with MOG or MOG-derived peptides revealed that only conformation-dependent Abs are associated with demyelinating activity, suggesting that epitope recognition is an important factor for Ab pathogenicity. Our findings provide novel and unexpected knowledge on the diversity of anti-MOG Ab responses in nonhuman primates and humans, and will permit the dissection of pathogenic auto-Ab properties in multiple sclerosis.     

Can we rely on public data as a source of information for cancer registry in developing countries?

BACKGROUND/AIMS: Although a "hospital-based cancer registry" is important in improving patient care, a "population-based cancer registry" with emphasis on epidemiology is important in allocating health care resources and prioritizing public health programs. Because of its reliance on retrieved clinical and para-clinical documents, there is some limitation in registering all cancer incidents in this system, especially in developing countries. In this study we examined the possibility of using public data as a complementary source of information for recording cancers in a population-based cancer registry. METHODS: Along with the annual census in rural areas, a survey was performed in Golestan province in March 2004 to identify public awareness about cancer incidents in the community. Individuals were questioned about history of cancer in their close relatives during the last two years. Those who reported cancer in their relatives were also asked to name the main organ of involvement. A similar list was retrieved from the cancer registry at the Ministry of Health in Gorgan, and cases with upper GI (esophagus and gastric) cancer diagnosis from 21 March 2002 through 20 March 2004 were selected for this study. Finally, these two lists were compared for examining accuracy of the collected data. RESULTS: We included 137 cases in our study with rural residence and known addresses. Only 35 (25.5%) cases were reported by the relatives and among them only 20 (57.1%) relatives correctly reported the tumor location. Although we found a difference in accurate reporting of cancer incidents by year of diagnosis (more correct cases reported during the second versus the first year), the difference was not statistically significant between the two years. CONCLUSION: In this study, we examined the possibility of using public awareness about cancer incidents as a complementary source of information for a population-based cancer registry. We found that this approach is not ideal for reducing limitations. Therefore, we recommend a nationwide cancer registry to record all cancer-related information at the time of diagnosis. This strategy will reduce the need for performing retrospective surveys in collecting cancer-related information.     

Expression and functional significance of an additional ligand for CTLA-4.

Effective T-cell activation requires antigen/major histocompatibility complex engagement by the T-cell receptor complex in concert with one or more costimulatory molecules. Recent studies have suggested that the B7 molecule, expressed on most antigen presenting cells, functions as a costimulatory molecule through its interaction with CD28 on T cells. Blocking the CD28/B7 interaction with CTLA4Ig inhibits T-cell activation in vitro and induces unresponsiveness. We demonstrate that another molecule(s), termed B7-2, is expressed constitutively on dendritic cells, is differentially regulated on B cells, and costimulates naive T cells responding to alloantigen. B7-2 is up-regulated by lipopolysaccharide in < 6 hr and is maximally expressed on the majority of B cells by 24 hr. In contrast, B7 is detected only on a subset of activated B cells late (48 hr) after stimulation. In addition, Con A directly induces B7-2 but not B7 expression on B cells. Finally, although both anti-B7 monoclonal antibodies and CTLA4Ig blocked T-cell proliferation to antigen-expressing B7 transfectants, only CTLA4Ig had any significant inhibitory effect on T-cell proliferation to antigens expressed on natural antigen presenting cells, such as dendritic cells. Thus, B7 is not the only costimulatory molecule capable of initiating T-cell responses since a second ligand, B7-2, can provide a necessary second signal for T-cell activation.     

One year after twin earthquakes in Northwest Iran

Every year in most earthquakes more than thousands of lives are lost, mainly in middle- and low-income countries. Disability and rehabilitation in third world countries could cause disastrous negative effect in living expense of families. So many preventable disabilities are result of these earthquakes and we hope reminding it will make a difference.     

Management of Complicated Aortic Aneurysms Using Multiple Overlapping Uncovered Stents: Mid-Term Outcome From a Cohort Study

This study sought to report the mid-term outcome of a modified flow-diverting strategy in the treatment of complicated aortic aneurysms of different morphology.Historical data suggested aortic aneurysm expansion and rupture after endovascular treatment with current commercial flow-diverters, indicating the essentiality of further investigation of this technique prior to its large-scale clinical application.An alternative flow-diverting strategy using layer-by-layer assembled multiple overlapping uncovered stents was employed in this study. The treatment outcome in aneurysms of different morphology (saccular, fusiform, and dissecting) was assessed during a mid-term follow-up period.Of 42 patients enrolled in this study (30 male, mean age: 63.3 years), technical success was achieved in 40 cases. During an average follow-up period of 20.9 months, mean aneurysm diameter shrunk from 53.4 ± 13.6 mm to 48.8 ± 13.9 mm (P < 0.001), while stent-induced sac thrombosis ratio increased significantly (18.1 ± 14.9% to 93.6 ± 9.5%, P < 0.001). The majority of side branches (74/76 major visceral branches, 237/244 minor segmental arteries), covered by 3.3 stents on average, maintained their patency after stenting. Saccular aneurysms manifested the highest thrombus deposition speed (18/20 were totally thrombosed within 12 months) and most significant shrinkage (51.4 ± 13.3 mm pre-operatively vs 43.5 ± 10.2 mm during follow-up, P < 0.001) compared with fusiform and dissecting aneurysms.This modified flow-diverting strategy could be a feasible alternative in the management of complicated aortic aneurysms where vital branches need to be preserved. The treatment outcome may depend on the aneurysm type. Further studies with larger patient cohort and longer follow-up are required to substantiate these results.