Isolated cor triatriatum sinistrum and pregnancy: case report and review of the literature

Purpose

Isolated cor triatriatum sinistrum (CTS) is a heart malformation in which a perforated fibromuscular membrane divides the left atrium into two chambers. When communication between these chambers is restricted, a patient may have signs and symptoms of mitral stenosis. The later stages of pregnancy are associated with tachycardia and increases in intravascular volume. We describe how this altered physiology may affect pregnant women with asymptomatic CTS. We also review the literature relating to pregnancy in patients with CTS.

Clinical features

A 30-yr-old primigravida, at 40 weeks of gestation with pre-pregnancy diagnosed asymptomatic CTS, was admitted for delivery. She had no cardiac symptoms during pregnancy, and her vaginal delivery under epidural analgesia was uneventful. This cardiac malformation is infrequently described in pregnant women, but a literature review showed that the physiology of late pregnancy with increases in hemodynamic variables may result in cardiac decompensation.

Conclusion

While our patient with isolated CTS and an unrestrictive intra-atrial membrane had an asymptomatic pregnancy and an uneventful labour, the literature review suggests that the increase in intravascular volume and heart rate that occurs during late pregnancy and after delivery may result in cardiac decompensation, even in patients with asymptomatic CTS.     

Micro-CT evaluation of the cortical bone micro-architecture in the anterior and posterior maxilla and the maxillary sinus floor

Objectives

To perform a within-subject comparison of the cortical bone micro-architecture of the maxillary sinus floor (MSF) to that of the buccal aspect of the anterior and posterior maxilla.

Methods

Micro-CT scans of the buccal aspect of the anterior and posterior maxilla and of the MSF in 14 human anatomical specimens were recorded. Within-subject comparisons were performed for cortical thickness (Ct.Th) and porosity (Ct.Po), average pore volume (AvgPo.V), and pore density (Po.Dn).

Results

The MSF presented the lowest and the anterior maxilla the highest Ct.Th, while Ct.Po was significantly higher at the MSF compared to the posterior maxilla (p = 0.021). No relevant differences were recorded for AvgPo.V and Po.Dn among regions (p > 0.067). Further, an increased Ct.Th at the MSF was significantly associated with a lower Po.Dn, while a higher Ct.Th and an increased AvgPo.V in the anterior maxilla were associated with a higher Ct.Th and an increased AvgPo.V, respectively, in the posterior maxilla and MSF. Finally, within each region, the AvgPo.V was associated positively with Ct.Po and negatively with Po.Dn.

Conclusions

The cortical bone of the MSF is slightly less thick and slightly more porous compared to the cortical bone at the buccal aspect of the anterior and posterior maxilla.

Clinical relevance

During lateral and vertical bone augmentation procedures, the cortical recipient bone is perforated several times to open the bone marrow compartment to facilitate provision of osteoinductive cells and molecules in the augmented space. Whether it is meaningful to approach the MSF in a similar way during MSF augmentation procedures or whether the slightly more porous structure of the MSF observed herein reduces the cortical barrier function already sufficiently has to be assessed in future clinical trials.

     

The Ljubljana classification - its application to grading oral epithelial hyperplasia.

INTRODUCTION: The diagnosis, prognosis and treatment of particular pathologic entities of the oral mucosa depend almost exclusively on the histologic changes in the epithelium. The basis for the classification of oral epithelial hyperplastic lesions should be their propensity to progress to invasive cancer.MATERIAL AND METHODS: In a retrospective study, 135 biopsies of oral epithelial hyperplastic lesions from 115 patients were classified according to the Ljubljana classification, which has recently been introduced for the grading of laryngeal hyperplastic epithelial lesions.RESULTS: Seventy nine cases (59%) showed simple, 42 (31%) abnormal and 11 (8%) atypical hyperplasia; carcinoma in situ was found in three cases (2%). During the follow-up, ranging from 3 months to 6 years (median 1 year), two cases of atypical hyperplasia progressed to invasive cancer, whereas none of the cases classified as simple or abnormal hyperplasia showed progression.CONCLUSION: The present study suggests that the Ljubljana classification can be reliably applied for classifying oral epithelial hyperplastic lesions into different risk groups, which is essential for prognosis in order to plan therapy.     

Complex I and ATP synthase mediate membrane depolarization and matrix acidification by isoflurane in mitochondria

Short application of the volatile anesthetic isoflurane at reperfusion after ischemia exerts strong protection of the heart against injury. Mild depolarization and acidification of the mitochondrial matrix are involved in the protective mechanisms of isoflurane, but the molecular basis for these changes is not clear. In this study, mitochondrial respiration, membrane potential, matrix pH, matrix swelling, ATP synthesis and -hydrolysis, and H(2)O(2) release were assessed in isolated mitochondria. We hypothesized that isoflurane induces mitochondrial depolarization and matrix acidification through direct action on both complex I and ATP synthase. With complex I-linked substrates, isoflurane (0.5mM) inhibited mitochondrial respiration by 28±10%, and slightly, but significantly depolarized membrane potential and decreased matrix pH. With complex II- and complex IV-linked substrates, respiration was not changed, but isoflurane still decreased matrix pH and depolarized mitochondrial membrane potential. Depolarization and matrix acidification were attenuated by inhibition of ATP synthase with oligomycin, but not by inhibition of mitochondrial ATP- and Ca(2+)-sensitive K(+) channels or uncoupling proteins. Isoflurane did not induce matrix swelling and did not affect ATP synthesis and hydrolysis, but decreased H(2)O(2) release in the presence of succinate in an oligomycin- and matrix pH-sensitive manner. Isoflurane modulated H(+) flux through ATP synthase in an oligomycin-sensitive manner. Our results indicate that isoflurane-induced mitochondrial depolarization and acidification occur due to inhibition of the electron transport chain at the site of complex I and increased proton flux through ATP synthase. K(+) channels and uncoupling proteins appear not to be involved in the direct effects of isoflurane on mitochondria.     

MurD enzymes from different bacteria: evaluation of inhibitors

D-Glutamic acid-adding enzyme (MurD ligase) catalyses the addition of D-glutamic acid to UDP-N-acetylmuramoyl-L-alanine, an essential cytoplasmic step in the pathway for bacterial cell-wall peptidoglycan synthesis. As such, it represents an important antibacterial drug-discovery target enzyme. Recently, several series of compounds have been synthesised and found to inhibit MurD from Escherichia coli, the best one having an IC(50) value of 8 μM. In the present work, we have tested 20 of these compounds against the MurD enzymes from Staphylococcus aureus, Streptococcus pneumoniae, Borrelia burgdorferi and Mycobacterium tuberculosis. Most of the E. coli MurD inhibitors appeared less efficient against the four other orthologues. This divergent result can be explained by the differences in amino acid sequences and topologies of the active sites of the MurD ligases studied.     

Structure-based design of a new series of D-glutamic acid based inhibitors of bacterial UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD)

MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of D-glutamic acid-based Escherichia coli MurD inhibitors incorporating the 5-benzylidenethiazolidin-4-one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC(50) between 3 and 7 μM). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC(50) values in the low micromolar range, represent the most potent D-Glu-based MurD inhibitors reported to date.