Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron

Background

Iron metabolism during pregnancy maintains fetal iron levels at the expense of the mother. The mechanism behind this regulation is still not clear despite recent advances. Here we examine the role of maternal and fetal Hfe, its downstream signaling molecule, hepcidin and dietary iron in the regulation of placental iron transfer.

Design and Methods

Hfe wild-type, knockout and heterozygote dams were fed iron deficient (12.5 ppm), adequate (50 ppm) and replete (150 ppm) iron diets and mated with heterozygote males to produce pups of all genotypes. Dams and pups were sacrificed at Day 18 of gestation; serum, placenta, body and liver iron parameters were measured. Protein and mRNA levels of various iron transporter genes were determined in duodenum, liver and placenta by Western blotting and real time PCR.

Results

Maternal liver iron levels were dependent on both dietary iron intake and Hfe genotype. Increasing iron levels in the maternal diet resulted in increased total iron in the fetus, primarily in the liver. However, fetuses of Hfe-knockout mothers showed further elevation of liver iron levels, concomitant with elevated expression of Tfr1, Dmt1 and Fpn in the placenta. Hfe-knockout fetuses that express low levels of liver hepcidin accumulated more iron in their liver than wild-type fetuses due to increased ferroportin levels in the placenta.

Conclusions

Maternal and fetal status, as well as dietary iron, is important in regulating iron transfer across placenta. Maternal Hfe regulates iron transfer by altering gene expression in the placenta. Fetal Hfe is important in regulating placental iron transfer by modulating fetal liver hepcidin expression.     

Hypericum-induced mood disorder: switch from depression to mixed episodes in two patients

Objective. To point out the danger of worsening mood disorders with the use of hypericum. Methods. Longitudinal clinical observation of two cases treated with hypericum. Results. The two patients underwent mixed episodes following hypericum treatment. One of them needed hospitalization for suicidal risk. Conclusion. Caution is warranted in the use of hypericum in depressed patients with hidden bipolarity. Patients should be informed that hypericum may induce manic symptoms, increase cycling of mood states, or worsen the depressive state.     

A Clinician’s Role in the Management of Soft Tissue Injuries of the Face: A Clinical Paper

Introduction

Injuries of the facial soft tissues may be due to road traffic accidents, industrial injuries, domestic and interpersonal violence, dog bites, human bites, war injuries etc. They may be described depending on the depth of involvement of the soft tissue and/or region since it gives the clinician the method of treatment. The soft tissue injuries must take into the underlying skeletal injury into account since these injuries if carelessly handled they leave deformed scarring in the most precious and beautiful part of the body.

Materials and Methods

Various patients reporting to the department of Oral and Maxillofacial Surgery, Narayana Dental College and hospital, Nellore were included in the study. Injuries in the various aspects of face at various anatomical areas has been presented with the mode of management.

Conclusion

The maxillofacial surgeon while attending these cases should avoid the need for revision by having a thorough knowledge of the anatomy, physiology of the soft tissues and treat them accordingly after following good clinical and radiological examination.     

Squamous variant of gallbladder cancer: is it different from adenocarcinoma?

Background

Literature on squamous variants of gallbladder cancer (GBC) is limited.

Methods

This was a retrospective analysis of GBC patients operated on between August 2009 and March 2012. Patients with adenosquamous carcinoma or squamous cell carcinoma were compared with adenocarcinoma for clinicopathologic features and surgical outcomes.

Results

Of the primary GBC patients resected with curative intent, 14 had adenosquamous carcinoma (10) or squamous cell carcinoma (4) (group A), whereas 122 had adenocarcinoma (group B). Abdominal pain was the most common symptom in both groups; however, presentation with vomiting and an abdominal lump was more common in group A (P = .04 and <.01, respectively). Group A had a significantly larger tumor size (7.9 vs 4.8 cm, P = .01) and a higher incidence of adjacent organ involvement requiring extended resections (85.7% vs 26.2%, P < .01). Despite the higher T stage, node-negative disease was significantly higher in group A (42.9% vs 17.2%, P = .03). There was no significant difference in the median survival after curative resection between the 2 groups (28 vs 31 months, P = .24).

Conclusions

The squamous variant of GBC presented at an advanced T stage; however, nodal involvement and distant metastasis were less common. Despite the higher T stage, curative resection could be achieved in the majority with a comparable survival.     

Th1 and Th17 cell subpopulations are enriched in the peripheral blood of patients with systemic juvenile idiopathic arthritis

Objective. The role of the adaptive immune system has not been explored in detail compared with the innate immune system in systemic JIA (sJIA) pathogenesis. The aim of this study was to examine the phenotype of circulating peripheral blood CD4(+) T-cell subpopulations in a cross-sectional study of sJIA patients during disease remission on medication and during acute flare of the disease. Methods. Flow cytometry was used to examine the phenotype and cytokine production of IFNγ-, IL-4- and IL-17-producing CD4(+) T cells in the peripheral blood of 10 sJIA patients with active disease, 9 sJIA with inactive disease, 14 JIA patients with oligoarticular onset, 10 adult control subjects and 10 age-matched control subjects. In parallel, we examined the proportion of FoxP3(+) Tregs. Results. IFNγ- and IL-17-producing CD4(+) T cells and IL-17-producing CD3(+)CD4(-) T cells were present at higher proportions in the peripheral blood of sJIA patients, irrespective of their disease status. Our data also confirm the known increase of the proportions of IFNγ-producing Th1 cells with increasing age and suggest an increase with age in the IL-17-producing CD4(+) T-cell population. Conclusion. This study is the first to describe significantly higher proportions of Th1 and Th17 T helper cell subsets in the peripheral blood of sJIA patients. These proinflammatory cells may play a pathogenic role in sJIA. Our data also emphasize the importance of using paediatric age-matched control subjects when evaluating the T-cell cytokine profile in JIA.     

An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

ABSTRACT: BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within [PLUS-MINUS SIGN]1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. METHODS: Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa--to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL from baseline. RESULTS: A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was [LESS-THAN OR EQUAL TO]29 weeks. Overall, the proportion of patients with hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2--13) to 54% (Weeks 18--25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. CONCLUSIONS: The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.Trial registrationClinicalTrials.gov registration: NCT00228449.     

Intraocular endoscopy: A review

Optimal visualization is one of the most challenging aspects of performing vitreoretinal surgery. In situations where conventional microscopic techniques provide poor posterior visualization, the adjunctive skill set of endoscopic visualization may be needed. This allows for by-passing the opaque anterior segment media and getting access to the posterior segment pathology. Endoscopic vitrectomy is a useful and unique adjunct to microincision vitreoretinal surgery. The optical set-up of endoscopy allows for clinical approaches that are impossible with regular microscope viewing systems. These include the ability to observe across optically significant anterior segment opacities and directly visualize the posterior segment of the eye. It also allows for visualizing the difficult-to-access retroirideal, retrolental, and anterior retinal structures. Surgical access to anatomic spaces like the pars plana, pars plicata, ciliary sulcus, ciliary body, and peripheral lens is tedious. This is made simpler by endoscopy. In this review, we summarize and review the usage of the intraocular endoscope as a diagnostic and therapeutic armamentarium across a wide spectrum of ocular pathologies.