Early development of the lower deciduous dentition and oral vestibule in human embryos

The aim of this work was to investigate the early development of the deciduous dentition and oral vestibule in the human embryonic lower jaw. Histological sections and three-dimensional reconstructions from prenatal weeks 6-9 were used. A continuous anlage for the oral vestibule did not exist in the mandible. In contrast to the upper jaw, where we previously observed that the dental and vestibular epithelia developed separately, two dento-vestibular bulges differentiated in the incisor region of the mandible. The lingual parts of each bulge were found to give rise to the respective central and lateral incisors, whereas the labial parts differentiated into the vestibular epithelium. In the canine and molar areas, the dental and vestibular epithelia originated separately. Later, the segments of the vestibular epithelium fused into the labial vestibular ridge, giving rise to the lower oral vestibule in the lip region. In the cheek region, the oral vestibule was found to originate in the mucosal inflection between the developing jaw and the cheek. A similar heterogeneous developmental base for the oral vestibule was also observed in the upper jaw. There is thus no general scheme for the early development of the dental and vestibular epithelia that applies to both the upper and lower jaws, and to both their anterior and posterior regions.     

Traumatic testicular dislocation

Introduction

Traumatic testicular dislocation is a rare entity. It occurs after a direct blunt scrotal trauma causing the testicle to migrate outside the scrotum, most frequently to the superficial inguinal region.

Materials and methods

A review of the diagnostic database of our two institutions was performed searching for complex genital trauma between 1990 and 2012.

Results

Seven cases of traumatic testicular dislocation were identified (four on the left side; one on the right side and two bilateral) for a total of nine testicles. Six were motorcycle accidents, and the other case suffered a pelvic crush injury. All victims had significant associated injuries, one case had an open dislocation and two were killed by the accident. The testicle was located at the inguinal region in four cases at the suprapubic area in four, and the other was an open dislocation. Diagnosis was suspected with the physical examination and confirmed by Doppler ultrasound; however, in one case, the diagnosis was missed during several weeks. In one case, the testicle was reduced into the scrotum immediately at the emergency department. Two cases were operated shortly after admission, performing testicular reduction into the scrotum and standard orchidopexy. Two other cases underwent delayed intervention, and both needed release of peri-testicular adhesions. Two cases (both bilateral) died at the accident site and were diagnosed by autopsy. In all surviving cases, it was possible to obtain a satisfactory orchidopexy with gonadal preservation.

Conclusions

Traumatic testicular dislocation is rare and diagnosis can be elusive. It should be suspected in motorcycle and high-energy accidents around the groin area and depends on a careful physical examination. With proper management, prognosis is excellent.     

Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material.     

Characterization of a Pyrazolo[4,3‐d]pyrimidine Inhibitor of Cyclin‐Dependent Kinases 2 and 5 and Aurora A With Pro‐Apoptotic and Anti‐Angiogenic Activity In Vitro

Selective inhibitors of kinases that regulate the cell cycle, such as cyclin‐dependent kinases (CDKs) and aurora kinases, could potentially become powerful tools for the treatment of cancer. We prepared and studied a series of 3,5,7‐trisubstituted pyrazolo[4,3‐d]pyrimidines, a new CDK inhibitor scaffold, to assess their CDK2 inhibitory and antiproliferative activities. A new compound, 2i , which preferentially inhibits CDK2, CDK5, and aurora A was identified. Both biochemical and cellular assays indicated that treatment with compound 2i caused the downregulation of cyclins A and B, the dephosphorylation of histone H3 at Ser10, and the induction of mitochondrial apoptosis in the HCT‐116 colon cancer cell line. It also reduced migration as well as tube and lamellipodia formation in human endothelial cells. The kinase inhibitory profile of compound 2i suggests that its anti‐angiogenic activity is linked to CDK5 inhibition. This dual mode of action involving apoptosis induction in cancer cells and the blocking of angiogenesis‐like activity in endothelial cells offers possible therapeutic potential.     

Design of a Unique Device for Residual Stresses Quantification by the Drilling Method Combining the PhotoStress and Digital Image Correlation

This paper presents a uniquely designed device combining the hole-drilling technique with two optical systems based on the PhotoStress and digital image correlation (DIC) method, where the digital image correlation system moves with the cutting tool. The authors aimed to verify whether the accuracy of the drilled hole according to ASTM E837-13a standard and the positioning accuracy of the device were sufficient to achieve accurate results. The experimental testing was performed on a thin specimen made from strain sensitive coating PS-1D, which allowed comparison of the results obtained by both methods. Although application of the PhotoStress method allows analysis of the strains at the edge of the cut hole, it requires a lot of experimenter’s practical skills to assess the results correctly. On the other hand, the DIC method allows digital processing of the measured data. However, the problem is not only to determine the data at the edge of the hole, the results also significantly depend on the smoothing levels used. The quantitative comparison of the results obtained was performed using finite element analysis.     

Double-chimaerism after transplantation of two human leucocyte antigen mismatched,unrelated cord blood units

The small number of progenitor cells is the major limitation to the use of umbilical cord blood (UCB) for the transplantation of adults. We tested the hypothesis that two units transplanted simultaneously could each contribute to haematopoietic reconstitution. A patient with advanced acute lymphocytic leukaemia received a mismatched, unrelated UCB transplant using units from two donors after conditioning. The recipient achieved a complete remission without graft-versus-host disease. Double chimaerism was documented in several leucocyte subpopulations; both units contributed to haematopoiesis until relapse. Triple chimaerism was present from relapse until death due to leukaemia. This approach may potentially improve UCB transplantation outcome for adults lacking a histocompatible donor.     

Preictal Dynamics of EEG Complexity in Intracranially Recorded Epileptic Seizure: A Case Report

Recent findings suggest that neural complexity reflecting a number of independent processes in the brain may characterize typical changes during epileptic seizures and may enable to describe preictal dynamics. With respect to previously reported findings suggesting specific changes in neural complexity during preictal period, we have used measure of pointwise correlation dimension (PD2) as a sensitive indicator of nonstationary changes in complexity of the electroencephalogram (EEG) signal. Although this measure of complexity in epileptic patients was previously reported by Feucht et al (Applications of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures. Med Biol Comput. 1999;37:208–217), it was not used to study changes in preictal dynamics. With this aim to study preictal changes of EEG complexity, we have examined signals from 11 multicontact depth (intracerebral) EEG electrodes located in 108 cortical and subcortical brain sites, and from 3 scalp EEG electrodes in a patient with intractable epilepsy, who underwent preoperative evaluation before epilepsy surgery. From those 108 EEG contacts, records related to 44 electrode contacts implanted into lesional structures and white matter were not included into the experimental analysis.The results show that in comparison to interictal period (at about 8–6 minutes before seizure onset), there was a statistically significant decrease in PD2 complexity in the preictal period at about 2 minutes before seizure onset in all 64 intracranial channels localized in various brain sites that were included into the analysis and in 3 scalp EEG channels as well. Presented results suggest that using PD2 in EEG analysis may have significant implications for research of preictal dynamics and prediction of epileptic seizures.