Maturational changes in connexin 43 expression in the seminiferous tubules may depend on thyroid hormone action

Introduction

Connexin 43 (Cx43) mediates the effect of thyroid hormone on Sertoli cell maturation in vitro. We investigated the influence of triiodothyronine (T3) administration on Cx43 expression in relation to the progress in seminiferous tubule maturation.

Material and methods

Male rats were daily injected with 100 µg T3/kg body weight from birth until postnatal day (pnd) 5 (transient treatment – tT3) or until pnd 15 (continuous treatment – cT3) or solvent – control (C). On pnd 16 serum hormone levels, body and testes weight, seminiferous tubule morphometry, Cx43 immunostaining and germ cell degeneration were investigated. Cx43 expression was also assessed in six 50-day-old adult untreated rats.

Result

tT3 increased 2.6-fold serum level of T3, testes weight, and seminiferous tubule diameter, and induced maturation-like dislocation of Cx43 expression from the apical to the peripheral region of Sertoli cell cytoplasm. In addition, incidence of Cx43-positive tubules declined from 86% in C to 46% after tT3, being similar to the adult value (30% of tubules Cx43-positive). In turn, cT3 increased serum T3 level 12-fold, and decreased body weight. Seminiferous tubules became shortened and distended, Sertoli cell cytoplasm vacuolated, Cx43 expression had minimal intensity and germ cell degeneration increased.

Conclusions

Cx43 might intermediate a short and transient stimulatory effect of T3 on seminiferous tubule maturation that disappeared together with exposure to the toxic effect of a continuously high level of the hormone.     

Operative field temperature during transnasal endoscopic cranial base procedures

Background

Data regarding the safety of endoscopic skull base exploration are very scarce. With this method, fragile vital structures (cranial nerves, the optic complex, brainstem, hypothalamus or cerebral ventricles) are exposed to direct illumination within a closed space. Also, high-speed drills, cauterization and ultrasonic aspiration deliver a significant load of thermal energy. The aim of this study was to record the temperature close to the structures of the skull base and in the intradural space during the procedures performed using extended endoscopic transnasal approaches.

Methods

The temperature of the skull base was continuously recorded during six transnasal endoscopic procedures. Implantable copper-constantan thermocouples were inserted: one into the esophagus and another through the nostril to reach the operative field at the skull base.

Results

At the beginning of the procedure, the temperature of the operative field was on average 36.8 °C?±?0.80 °C, i.e. only 1 °C higher than the esophageal temperature. Then it grew continuously during the whole procedure, to eventually reach a level of 42–43 °C at the final stage, whereas the esophageal temperature remained stable. Occasionally, the temperature increased up to 45 °C during cauterization and ultrasonic aspiration, and even up to 62 °C during high-speed drilling.

Conclusion

Endoscopic skull base surgery is associated with an incessant increase of the temperature of the intraoperative field. The temperature can peak suddenly to levels which can potentially harm neural structures and influence the rate of postoperative complications.     

Elevation of pulmonary artery pressure as a complication of nilotinib therapy for chronic myeloid leukemia

We present the case of a 72-year-old male with chronic phase myeloid leukemia. Elevation of the pulmonary artery pressure due to nilotinib therapy was noted. This effect on pulmonary artery pressure was nilotinib dose dependent.     

Changes in condylar cartilage after anterior mandibular displacement in juvenile pigs

Adaptive remodelling of the mandibular condyle in response to mandibular advancement is the mechanism exploited by orthodontic forward displacement devices.ObjectiveThis work investigated the expression of collagens, matrix metalloproteinases and vascular endothelial growth factor during this process.DesignTwenty juvenile pigs were randomly divided into two experimental groups, where the treatment group was fitted with mandibular advancement splints, and the control group was not. Changes in the mRNA content of condylar cartilage tissue was then were measured by real-time PCR using specific primers after 4 weeks of treatment.ResultsThe temporal pattern of the expression of Col1 and MMP13 during condylar adaptation coincided with that during natural condylar growth. The amount of the expression of Col10 during condylar adaptation was significantly lower (p < 0.05), whereas the expression of Col2, MMP8 and VEGF was significantly higher compared to natural growth (p < 0.05).ConclusionsIt is suggested that condylar adaptation in growing pigs triggered by mandibular forward positioning results not only from passive adaptation of cartilage, but also involves growth affected processes. Our results showed that mechanical strain produced by mandibular advancement induced remodelling and revascularization in the posteriocranial mandibular condyle. These results are mostly consistent with former published histological and histomorphometrical analyses.     

Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study

Background and purposeThe common treatment in patients with newly diagnosed glioblastoma multiforme is the ultimately radical surgical removal of the tumour combined with radiotherapy. This study compared safety and efficacy of radiotherapy alone with radiotherapy combined with temozolomide (TMZ) given before, during, and after radiotherapy.Material and methodsThe patients operated on for glioblastoma multiforme during the first 21 postoperative days were randomly assigned to the group treated with radiotherapy alone (involved-field radiotherapy in 2 Gy fractions daily five times a week up to the total of 60 Gy over 6 weeks of treatment) or to the group treated with radiotherapy and TMZ, initially in the dose of 200 mg/m² during 5 postoperative days and after 23 days followed by 75 mg/m² of body surface area daily, 7 days a week (from the first to the last day of radiotherapy). On completion of radiotherapy, five complementary courses of TMZ were introduced (150–200 mg/m² for 5 days, repeated every 28 days). The primary outcome measure was overall survival.ResultsFifty-eight patients from 3 centres were included in the study. The mean age of patients was 55 years and all the patients underwent a surgical procedure of glioblastoma removal. The mean overall survival in the group treated with TMZ was 16.0 months, whereas in the group with radiotherapy alone the overall survival reached 12.5 months. 24-month survival reached 23% in patients treated with TMZ and 6.7% in those who received radiotherapy only. Haematological complications of third or fourth degree were present in 10% of patients treated with radiotherapy and TMZ.ConclusionsThe introduction of TMZ before, during and after radiotherapy for newly diagnosed glioblastoma multiforme gives clinically and statistically significant improvement of survival with unremarkably increased toxicity of the treatment.     

Relaxin‐3 innervation of the intergeniculate leaflet of the rat thalamus – neuronal tract‐tracing and in vitro electrophysiological studies

Behavioural state is controlled by a range of neural systems that are sensitive to internal and external stimuli. The relaxin‐3 and relaxin family peptide receptor 3 (RXFP3) system has emerged as a putative ascending arousal network with putative involvement in regulation of stress responses, neuroendocrine control, feeding and metabolism, circadian activity and cognition. Relaxin‐3/γ‐aminobutyric acid neuron populations have been identified in the nucleus incertus, pontine raphe nucleus, periaqueductal grey (PAG) and an area dorsal to the substantia nigra. Relaxin‐3‐positive fibres/terminals densely innervate arousal‐related structures in the brainstem, hypothalamus and limbic forebrain, but the functional significance of the heterogeneous relaxin‐3 neuron distribution and its inputs to specific brain areas are unclear. Therefore, in this study, we used neuronal tract‐tracing and immunofluorescence staining to explore the source of the dense relaxin‐3 innervation of the intergeniculate leaflet (IGL) of the thalamus, a component of the neural circadian timing system. Confocal microscopy analysis revealed that relaxin‐3‐positive neurons retrogradely labelled from the IGL were predominantly present in the PAG and these neurons expressed corticotropin‐releasing factor receptor‐like immunoreactivity. Subsequently, whole‐cell patch‐clamp recordings revealed heterogeneous effects of RXFP3 activation in the IGL by the RXFP3 agonist, relaxin‐3 B‐chain/insulin‐like peptide‐5 A‐chain (R3/I5). Identified, neuropeptide Y‐positive IGL neurons, known to influence suprachiasmatic nucleus activity, were excited by R3/I5, whereas neurons of unidentified neurotransmitter content were either depolarized or displayed a decrease in action potential firing and/or membrane potential hyperpolarization. Our data identify a PAG to IGL relaxin‐3/RXFP3 pathway that might convey stress‐related information to key elements of the circadian system and influence behavioural state rhythmicity.     

The generation of theta rhythm in hippocampal formation maintained in vitro

The most spectacular example of oscillations and synchrony which appear in the brain is the rhythmic slow activity (theta) of the limbic cortex. Theta rhythm is the best synchronized electroencephalographic activity that can be recorded from the mammalian brain. Hippocampal formation is considered to be the main structure involved in the generation of this activity. Although detailed studies of the physiology and pharmacology of theta‐band oscillations have been carried out since the early 1950s, the first demonstration of atropine‐sensitive theta rhythm, recorded in completely deafferented hippocampal slices of a rat, was performed in the second half of the 1980s. Since the discovery of cholinergically induced in vitro theta rhythm recorded from hippocampal formation slices, the central mechanisms underlying theta generation have been successfully studied in in vitro conditions. Most of these experiments were focused on the basic question regarding the similarities between the cholinergically induced theta activity and theta rhythm examined in vivo. The results of numerous in vitro experiments strongly suggest that cholinergically induced theta rhythm recorded in hippocampal slices is a useful analogue of theta observed in intact animals, and could be helpful in searching for the mechanisms of oscillations and synchrony in the central nervous system neuronal networks. The objective of the present review is to discuss the main results of experiments concerning theta oscillations recorded in in vitro conditions. It is our intent to provide, on the basis of these results, the characteristics of essential mechanisms underlying the generation of atropine‐sensitive in vitro theta.