Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway

Protein tyrosine kinase 7 (PTK7) is a pseudokinase whose precise function in regulating angiogenesis remains unknown. The purpose of this study was to define the mechanisms by which PTK7 promotes vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis in vivo and in vitro. Immunoblotting was used to measure PTK7 expression in several types of vascular endothelial cells. Using both immunoprecipitation and immunoblotting, PTK7 was found to join a receptor complex with Flt-1 (VEGFR1), but not with KDR/Flk-1 (VEGFR2) or with Flt-4 (VEGFR3). By surface plasmon resonance analysis, the interaction between Flt-1 and PTK7 was confirmed and found to be intensified by VEGF-A. Flt-1 phosphorylation and downstream signals of Akt, and focal adhesion kinase (FAK) thus induced were down-regulated by inhibition of PTK7 expression using siRNA. Moreover, PTK7 overexpression in endothelial cells resulted in enhanced angiogenesis in vitro. In contrast, neovascularization induced in vivo by VEGF-A pellets was significantly decreased by injection of siRNA targeting PTK7. These data suggest that PTK7 serves an essential role in Flt-1-mediated angiogenesis.     

Immune Responses to Antigens of in vitro Reared Echinococcus granulosus Adult Worms in Balb/c Mice

Background: Cystic echinococcosis (CE), also known as echinococcosis/hydatidosis, is one of the most important parasitic diseases in the world. It enhances both humoral and cellular (Th1 and Th2) responses in infected host. Different antigens of the worm may favor the Th1 or Th2 immune responses in CE patients. Objective: To evaluate the humoral and cellular immune responses of Balb/c mice against the crude and excretory/secretory (E/S) antigens of in vitro reared Echinococcus granulosus adult worms. Methods: A total of 20 Balb/c mice divided into 5 groups of 4 mice each. Three groups of mice (n=4) were immunized with crude, E/S and an immunodominant antigen of in vitro reared Echinococcus granulosus adult worms on day 1 and 28. The fourth and the fifth groups were negative control groups and received PBS plus adjuvant, or nothing, respectively. Two weeks after the second injection, the mice were killed and their blood was collected for determining antibody responses, and their spleens were employed for proliferation assay. Total IgG was measured by indirect ELISA. Spleen cells of immunized mice were cultivated and exposed to different antigens of adult worms including E/S and crude antigens. Levels of IFN-γ, IL-12, IL-4 and IL-10 were measured in the recovered cell culture supernatants by capture ELISA. Results: Total IgG assay showed the highest level of antibody produced in mice immunized with crude antigens. Proliferation assay showed a statistically significant production of cytokines in the mice immunized with crude antigens (p<0.05). The highest levels of IFN-γ, IL-12 and IL-4 were produced in mice immunized with crude antigen of the in vitro reared Echinococcus granulosus adult worms followed by E/S antigens. Immunodomonant antigen induced the lowest levels of cytokines (IL-12, IFN-γ, IL-4 and IL-10) in immunized mice. Conclusion: Significant levels of Th1 related cytokines (IFN-γ and IL-12) were produced in Balb/c mice immunized with crude antigen of the in vitro reared Echinococcus granulosus adult worms.     

Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease

Background

Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain.

Objectives

We examined the ATP7B mutation spectrum in Wilson disease patients in Iran.

Patients and Methods

Genomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing.

Results

We identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population.

Conclusions

Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients     

Hepatitis C and hepatitis B virus infection: epidemiology and risk factors in a large cohort of pregnant women in Lorestan, West of Iran

Background

There are little data on the prevalence of serological markers of hepatitis B and hepatitis C viruses in pregnant women in Iran.

Objectives

This study was designed to determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among pregnant women in Lorestan, west of Iran.

Patients and Methods

Serum samples of 827 pregnant women who lived in rural (36.8%) and urban areas (63.2%) of Lorestan were collected during 2007-2008. Data were obtained through questionnaires. Samples were first screened for anti-HCV and anti-HBc by ELISA. Those who were positive for anti-HBc were tested for HBsAg.

Results

Anti-HBc was found in 28 of 827 pregnant women (overall prevalence, 3.4%; 14 of 523 in urban areas, 2.7%; 14 of 304 in rural areas, 4.6%). Of the 28 positive samples, 6(0.7%) were positive for HBs-Ag. Only 2 samples (0.2%) were anti-HCV-positive.

Conclusions

These results underscore the need for prenatal screening for HBV infection in pregnant women and treatment of newborns from HBsAg-positive mothers.More studies are needed to identify risk factors of HCV infection and highlight the importance of HCV screening and treatment programs.     

The Role of Marital Status,Literacy, and Urbanity in Suicidal Behavior by Burns in the Province of Khorasan,Iran

A prospective study of all suicidal behaviors by burns requiring hospitalization was conducted in the province of Khorasan, Iran, from March 21, 2005 to March 20, 2006, to examine marital status, urbanity and literacy among these patients. Data were obtained through interviews during the course of hospitalization. A total of 130 patients with suicidal behavior by burns were identified (incidence rate of 2.9 per 100,000). Females had a higher rate of suicidal behavior by burns than males (4.2 vs. 1.6 per 100,000, P < 0.001). The rate of suicidal behavior by burns was higher among single persons than married persons (4.3 vs. 3.5 per 100,000). The rate of suicidal behavior by burns among the rural population was slightly higher than the urban population (3.2 vs. 2.7 per 100,000). The high rate of suicidal behavior by burns among young, married women in Khorasan is a social tragedy.     

Modified retro-tubercle opening-wedge versus conventional high tibial osteotomy

Despite the fact that common surgical techniques for the treatment of genu varum usually correct the malalignment in the affected knee, these methods have significant complications and cause problems in the long term. Retro-tubercle opening-wedge high tibial osteotomy is among the newer techniques for the treatment of genu varum. The goal of this study was to compare the results of retro-tubercle opening-wedge high tibial osteotomy with those of medial opening-wedge osteotomy. In a randomized, controlled trial, 72 patients with varus knees who were scheduled for surgery were assigned into either the retro-tubercle opening-wedge high tibial osteotomy (n=34) or medial opening-wedge osteotomy groups (n=38). Groups were matched for age and sex. The position of the patella was compared with respect to the tuberosity and the upper tibial slope pre- and postoperatively. Patients were followed for an average of 13 months (range, 10-21 months). In the retro-tubercle opening-wedge high tibial osteotomy group, the length of the patellar tendon did not significantly differ pre- and postoperatively (P≥.5); however, in the medial opening-wedge osteotomy group, a statistically significant shortening was noted in patellar tendon postoperatively (P≤.05). Similarly, the tibial plateau inclination showed a statistically significant difference postoperatively in the medial opening-wedge osteotomy group, while the difference in the retro-tubercle opening-wedge high tibial osteotomy group did not reach statistical significance.