Time-course of the electrophysiological maturation and integration of transplanted cardiomyocytes

Electrophysiological maturation and integration of transplanted cardiomyocytes are essential to enhance safety and efficiency of cell replacement therapy. Yet, little is known about these important processes. The aim of our study was to perform a detailed analysis of electrophysiological maturation and integration of transplanted cardiomyocytes. Fetal cardiomyocytes expressing enhanced green fluorescent protein were transplanted into cryoinjured mouse hearts. At 6, 9 and 12days after transplantation, viable slices of recipient hearts were prepared and action potentials of transplanted and host cardiomyocytes within the slices were recorded by microelectrodes. In transplanted cells embedded in healthy host myocardium, action potential duration at 50% repolarization (APD50) decreased from 32.2±3.3ms at day 6 to 27.9±2.6ms at day 9 and 19.6±1.6ms at day 12. The latter value matched the APD50 of host cells (20.5±3.2ms, P=0.78). Integration improved in the course of time: 26% of cells at day 6 and 53% at day 12 revealed no conduction blocks up to a stimulation frequency of 10Hz. APD50 was inversely correlated to the quality of electrical integration. In transplanted cells embedded into the cryoinjury, which showed no electrical integration, APD50 was 49.2±4.3ms at day 12. Fetal cardiomyocytes transplanted into healthy myocardium integrate electrically and mature after transplantation, their action potential properties after 12days are comparable to those of host cardiomyocytes. Quality of electrical integration improves over time, but conduction blocks still occur at day 12 after transplantation. The pace of maturation correlates with the quality of electrical integration. Transplanted cells embedded in cryoinjured tissue still possess immature electrophysiological properties after 12days.     

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.     

Tegillarca granosa extract Haishengsu (HSS) suppresses expression of mdr1, BCR/ABL and sorcin in drug-resistant K562/ADM tumors in mice

PurposeTo evaluate the effect of Haishengsu (HSS), a protein extract from Tegillarca granosa, on multidrug-resistance genes mdr1, BCR/ABL and sorcin in transplanted tumors.Material/MethodsMice were inoculated subcutaneously with a drug resistant leukemia cell line K562/ADM. Tumor-bearing animals were divided into control, adriamycin, HSS and combination therapy (adriamycin plus HSS) groups. Flow cytometry was used to detect apoptosis of tumor cells, and RT-PCR was used to evaluate the expression of mdr1, BCR/ABL and sorcin.ResultsThe apoptosis rate in the high (71.8%), medium (72.3%) and low doses HSS group (72.4%) was higher than in control (1.2%, p<0.01), adriamycin (34.4%, p<0.05) or combination therapy group (46.4%, p<0.05). The mean optical density of mdr1, BCR/ABL and sorcin in HSS groups was lower than in control, adriamycin and combination therapy group (p<0.01). The optical density of the three genes in high HSS group was lower than in medium and low HSS group (p<0.01).ConclusionsHaishengsu promotes apoptosis of drug-resistant K562/ADM tumors in mice in a dose-dependent manner. The pro-apoptotic effect of Haishengsu may be related to a reduced expression of multidrug-resistance genes mdr1, BCR/ABL and sorcin.     

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.