A case of persistent left and absent right superior caval vein: An anatomical and embryological perspective.

The relatively common persistent left superior caval vein (LSCV) is in most cases associated with doubling of the superior caval vein. A persistent LSCV with absent right superior caval vein (RSCV)-a rather rare event-was found during our course of gross anatomy. The LSCV drained into an enlarged coronary sinus, which was partly accompanied by an apparent "double" sinus of normal size draining into this enlarged coronary sinus. Histological and immunofluorescence studies using antibodies against smooth and cardiac muscle actins were performed. The terminal part of the LSCV near the opening into the right atrium contained cardiac actin as expected for a normal derivative of the left sinus horn. Previously only one case of doubled coronary sinus with LSCV has been reported and this abnormality was explained by splitting of the sinus. In our case, the partly doubled coronary sinus had the structure of coronary veins. Mechanical forces have been invoked for the obliteration of the LSCV. Therefore, we examined thirteen human embryos from 15 mm to 32 mm crown-rump length. In one embryo, we found a persistent LSCV together with an enormously enlarged left atrium. Contrary to previous suggestions our data indicate that during normal development a compression of the left anterior cardinal vein does not sufficiently explain the obliteration of the left and the persistence of the right vein. We therefore believe that beside a left dominated blood flow of head and arm, genes for left-right signaling may have to be taken into consideration.

Chromatin breakdown by deoxyribonuclease1 promotes acetaminophen-induced liver necrosis: an ultrastructural and histochemical study on male CD-1 mice.

We analyzed in male wild-type (WT) and Dnase1 knockout (KO) CD-1 mice after acetaminophen (APAP)-intoxication the hepatolobular distribution of APAP-adducts in relation to DNA-damage by terminal deoxyribonucleotidyl-transferase dUTP nick end-labeling (TUNEL), the ultrastructural alterations of hepatocellular morphology and the intracellular localization of Dnase1. Treatment of WT-mice with 600 mg/kg APAP led to extensive pericentral necrosis. Electron microscopy (EM) demonstrated vesiculation of the rough endoplasmatic reticulum and swelling of mitochondria. Pericentral WT-hepatocyte nuclei exhibited pyknosis, karyorrhexis and karyolysis. In contrast, livers from treated KO-mice exhibited almost normal light microscopical structure and EM revealed only mild signs of hepatocellular damage. In WT-mice several layers of pericentral hepatocytes displayed APAP-adduct formation and subsequent DNA-damage, whereas in KO-animals only few cells were affected. Serum aminotransferases rose similarly in both mouse strains up to 12 h, thereafter increased only in WT-mice. Immunogold-EM revealed the translocation of Dnase1 from the rER into the nuclei of treated WT-mice. In KO-mice, APAP-adduct formation was retarded and less extensive suggesting that detoxification of APAP must have been more effective in KO-mice possibly due to the lack of energy depletion otherwise caused by Dnase1-induced DNA-damage in WT-mice.

Contribution to the origin and development of the appendices of the testis and epididymis in humans.

Hydatids, as appendices of testis or epididymis, were discovered by Morgagni in 1703 and 1705 and published by him in 1761. Hydatids are considered to be remnants of the cranial part of the Mullerian duct (MD), Wolffian duct (WD), or mesonephric tubules. They are localized as sessile or pedunculated appendices at the cranial pole of testis and at the head of epididymis, or at analogous organs in women. The clinical relevance is known: acute scrotum with torsion of appendices, or metaplasia. However, little is known about the embryological development of hydatids. Therefore, we studied the origin and development of appendix testis (AT) and appendix epididymidis (AE) in human embryos from stage 14 (Carnegie Collection), 6.5 mm GL, 32 days, to fetuses of 170 mm, 17th week. Light and scanning-electron microscopy as well as plastic reconstructions from serial sections of the cranial parts of MD and WD reveal that hydatids already form during regression or transformation of the ducts. At stage 18, 15-16 mm GL, 44 days, the cranial parts of MD and WD exhibit morphological features that give a preview on the definite form and position of later appendices. In fetuses from 45 mm GL, ninth week onward, we found anlagen of pedunculated hydatids (AE) deriving from the ampullated cranial end of the WD, which in many cases opened into the coelomic cavity. The unpedunculated AT derived from the persisting funnel region of the MD. The development of duct-independent, accessory appendices was observed. We paid special attention to a pedunculated hydatid in a fetus of 120 mm, 14th week, and the cranial regressing WD. A classification of hydatids is presented. Photographs and histological sections of (sessile) appendices testis (AT), and (pedunculated) appendices epididymidis (AE) with torsion of stalks exhibit the final forms and positions of hydatids in adult.

The structural examination of myocardial samples from patients with end-stage heart failure supported by ventricular assist devices using electron microscopy and amino acid analysis reveals low degree of reverse remodeling.

BACKGROUND: Chronic heart failure is a multifactorial, progressive disease of many causes and is associated with complex ventricular remodeling. Deposition of extracellular matrix proteins and sarcomeric disarray of the myocytes occur in end-stage heart failure. Ventricular assist devices (VAD), implanted as bridge to transplantation, may reverse ventricular remodeling. Although successfully weaning patients from VAD support has been reported, it is not clear to what degree reversal of remodeling occurs in unloaded failing hearts. Because collagen deposition and ultrastructural disarray are hallmarks of myocardial remodeling, we analyzed the myocardial ultrastructure and collagen content of VAD-supported hearts before and after mechanical unloading. METHODS: We used amino acid analysis to measure collagen content (4-hydroxyproline content) in 24 transplant candidates receiving VAD support. We used transmission electron microscopy to examine the ultrastructure in 6 patients receiving VAD support. RESULTS: The 4-hydroxyproline content increased significantly at VAD implantation and was not altered by mechanical unloading. The ultrastructure showed signs of persisting cardiomyopathy. CONCLUSION: Mechanical unloading does not alter the total collagen content of the supported, failing heart. Thus, structural reversal of the remodeling process associated with heart failure is not a general phenomenon in mechanically unloaded hearts.

Cold-induced apoptosis of rat liver endothelial cells: contribution of mitochondrial alterations.

BACKGROUND: Maintenance of the integrity of the vascular endothelium is a critical issue in liver preservation, but hypothermia, applied for cellular protection, induces apoptotic cell death in liver endothelial cells. This cold-induced apoptosis is mediated by an iron-dependent formation of reactive oxygen species. Here, we study the involvement of mitochondria in this process. METHODS: Cultured rat liver endothelial cells were incubated in cold University of Wisconsin solution for 18 hr and subsequently rewarmed in cell culture medium. Mitochondrial morphology and membrane potential were evaluated using laser scanning microscopy. RESULTS: During cold incubation in University of Wisconsin solution, a marked, progressive mitochondrial shortening and a reduction in mitochondrial membrane potential occurred. Rewarming of the cells led to mitochondrial ultracondensation, complete loss of the mitochondrial membrane potential, and subsequent apoptotic cell death. The inhibitors of mitochondrial permeability transition, trifluoperazine and fructose, or iron chelation with deferoxamine did not affect mitochondrial shortening during cold incubation but inhibited ultracondensation, loss of mitochondrial membrane potential, and loss of viability during rewarming. Moreover, in these protected cells, an almost complete reestablishment of the mitochondrial membrane potential and morphology could be observed; the few mitochondria that were irreversibly damaged were incorporated into autophagosomes during cellular recovery. CONCLUSION: Two apparently independent mitochondrial alterations take place during cold incubation and subsequent rewarming of liver endothelial cells. Cold-induced mitochondrial shortening represents a reversible process, whereas iron-mediated mitochondrial permeability transition and ultracondensation during rewarming are irreversible and constitute an important mediator of cold-induced apoptosis.

The morphology of the rostral notochord in embryos of Ichthyophis kohtaoensis (Amphibia, Gymnophiona) is comparable to that of higher vertebrates.

The rostral notochord plays an important role in the head development of vertebrates. Yet, in contrast to trunk notochord, the course and behavior of the head notochord shows species-specific variations. To analyze normal and abnormal development in the head region, knowledge of the normal behavior of the rostral notochord is a prerequisite. Therefore, we studied the rostral notochord of Ichthyophis kohtaoensis, not only in anatomical view a relatively unknown order of Gymnophiona, in embryos of the stages B, C, D, E according to Himstedt (1996) or stages 21, 22, 26, 31 according to Dünker et al. (2000). We described the course, form, and structure of this part of the notochord and compared it with morphological features and variations of the notochord in existing studies of higher vertebrates (Barteczko and Jacob 1999). We found that the rostral notochord of this oviparous Gymnophiona from Thailand is quite similar to that of higher vertebrates: its tendency to elongate directly in a rostral direction is prevented by the adenohypophysis as a barrier; at stage B the neurohypophysis/infundibulum takes the role of a hindrance. Light microscopic results, laser scanning micrographs, and plastic reconstructions based on serial sections showed unequivocally in stages B-E the effects resulting from this hindrance: buckling, variations in volume, screw-like torsions, undulations, deviations, and splintering. The notochord was found to lie dorsal to the developing cartilaginous basicranium. The tendency to press the dura towards the brain was conspicuous. The formation of a bursa pharyngea was likewise observed; the predisposition of several such structures exist. We suggest that the vertebrate phenotype with the appearance of preaxial structures, in contrast to the chordata phenotype, correlate with the formation of a hypophysis. Experiments have yet to prove this hypothesis.