RETROSPECTIVE STUDY OF MORBIDITY AND MORTALITY IN A CAPTIVE POPULATION OF CRYPTOSPORIDIUM-POSITIVE LOUISIANA PINE SNAKES (PITUOPHIS RUTHVENI).

The Louisiana pine snake (Pituophis ruthveni) is a diurnal colubrid species native to Louisiana and eastern Texas whose free-ranging populations have been declining over at least the past 30 yr. The creation and maintenance of sustainable captive breeding programs of P. ruthveni to restore native populations has also provided ample opportunity for research into this species and for P. ruthveni to serve as a research model for other colubrid snakes. However, no investigation into prevalent causes of morbidity and mortality in captive populations of this species has been described. A research population of P. ruthveni was maintained at Louisiana State University (LSU) for over 4 yr due to unsuitability for breeding after testing positive for Cryptosporidium serpentis. Since arrival at LSU, the snakes were under close veterinary surveillance. Complete postmortem examinations were performed on 12 snakes that died or were euthanized. The aim of this study was to further understanding of common factors influencing morbidity and mortality in captive P. ruthveni infected with C. serpentis, by retrospectively reviewing postmortem exam findings from the 12 deceased members of the population at LSU. A predominant finding across individuals included bacterial infections, which were responsible for major illness or death in 37.5% of the animals. Fifty percent of snakes tested positive for Cryptosporidium sp. based on PCR performed from postmortem samples; it was directly implicated as cause of death or morbidity in 83.3% of positive cases. Although infectious disease represented the most common pathologic postmortem finding, several noninfectious disease processes were identified, including gout, goiter, and neoplasia. These findings mirror those of other retrospective investigations of reptile collections at various institutions and highlight the need for appropriate emphasis on the identification, treatment, and prevention of infectious disease as part of routine veterinary care.

Human bone marrow-derived mesenchymal stem cells rescue neonatal CPAP-induced airway hyperreactivity.

Continuous positive airway pressure (CPAP) is a primary non-invasive mode of respiratory support for preterm infants. However, emerging evidence suggests CPAP could be an underlying contributor to the unintended pathophysiology of wheezing and associated airway hyperreactivity (AHR) in former preterm infants. The therapeutic benefits of mesenchymal stem cells (MSCs) have been demonstrated in a variety of animal models and several clinical trials are currently underway to assess their safety profiles in the setting of prematurity and bronchopulmonary dysplasia (BPD). In the present study, using a mouse model of neonatal CPAP, we investigated whether conditioned medium harvested from cultures of human bone-marrow derived mesenchymal stem cells (hMSC) could rescue the CPAP-induced AHR, based upon previous observations of their anti-AHR properties. Newborn mice (male and female) were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for the first 7 postnatal days. At postnatal day 21 (two weeks after CPAP ended), lungs were removed, precision-cut lung slices were sectioned and incubated for 48 h in vitro in conditioned medium collected from cultures of three different hMSC donors. As expected, CPAP resulted in AHR to methacholine compared to untreated control mice. hMSC conditioned medium from the cultures of all three donors completely reversed AHR. These data reveal potential therapeutic benefits of hMSC therapy, which may be capable of rescuing the long-term adverse effects of neonatal CPAP on human airway function.

[Intraoperative OCT in retinal detachment with macular involvement]. / Intraoperative OCT bei Netzhautablösung mit Makulabeteiligung.

BACKGROUND: Intraoperative optical coherence tomography (iOCT) has recently been introduced for the visualization of retinal structures within the operating microscope. OBJECTIVE: The aim of this study was to analyze the behavior of the retina and morphological features during surgery for retinal detachment with macular involvement. METHODS: A retrospective analysis of 41 consecutive eyes with macula-off retinal detachment, which were treated with pars plana vitrectomy (PPV) using iOCT. A qualitative analysis of morphological features of the retina at defined moments during surgery was carried out. RESULTS: The visualization of macular detachment with iOCT was successful in 63% of cases and in the other cases the height of retinal detachment surpassed the maximum depth of the scan by iOCT. With perfluorodecalin 53.7% of eyes showed subretinal fluid and 22% of eyes showed a wave-like configuration of the outer retinal layers. In 61% of the eyes persisting subretinal fluid could be detected under the final tamponade. The amount of subretinal fluid could not be detected intraoperatively with the naked eye. In one case a macular hole could be newly identified intraoperatively and in three cases macular detachment could not be found at the start of surgery, although a detachment had been expected. CONCLUSION: The use of iOCT rarely leads to changes or extension of the intervention; however, it provides real-time information on intraretinal and subretinal fluid, which is sometimes in contrast to the clinical assessment. The relevance of persistent subretinal fluid and folds of the outer retinal layers after surgery remains unclear. It can be speculated whether this could serve as a prognostic factor for the postoperative outcome.

Caffeine prevents prostaglandin E1-induced disturbances in respiratory control in neonatal rats: implications for infants with critical congenital heart disease.

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.

The learning curve of patient-specific unikondylar arthroplasty may be advantageous to off-the-shelf implants: A preliminary study.

INTRODUCTION: Introducing a new arthroplasty system into clinical routine is challenging and could have an effect on early results. Since UKA are known to have failure mechanisms related to technical factors, reliable results and easy adoption are ideal. The question remains whether there are differences in objective procedure parameters in the early learning curve of different UKA systems. METHODS: two different UKA implants (Biomet Oxford[BO] followed by Conformis iuni[CI]) were introduced consecutively into clinical routine. We retrospectively analyzed the first 20 cases of each implant for one arthroplasty surgeon regarding operating time, correction of the mechanical axis, learning curve parameters, and revision rate of implants for 1.5 years postoperatively. RESULTS: Operating time (BO:98.3 ± 26.3min, CI:83.85 ± 21.8min (p < 0.078)), and tourniquet time differed in favor of the CI implant (BO:97.5 ± 29.5min; CI:73.5 ± 33.2 min; p < 0.017)). Mechanical alignment was restored in boths (preop:BO:mean 2.9°varus, CI:2.7°varus, postop:BOmean1.3°varus, CI:1°varus), while one BO patient and two CI patients were overcorrected. Operating time decreased from the first five implants to implants 16-20 for CI (95.2 ± 18.5min to 69 ± 21.5min, p < 0.076) and BO (130.6 ± 27.6min to 78 ± 17.3min, p < 0.009). Within 18 months of follow-up, 2 BO and 1 CI implants were revised. CONCLUSION: The introduction of an UKA implant was associated with longer surgery in both implants. Procedure time seems to differ between implants, while a learning curve was observed regarding instrumentation. CI implants seem to be reliable and adaptable in a medium-volume practice. The early results of this retrospective single-surgeon study were in favor of the individualized implant. Certainly, further studies encompassing larger cohorts with various implants are needed.

Who cares? The impact on caregivers of suspected mining-related lung cancer.

Background: In the present study, we investigated the emotional, physical, financial, occupational, practical, and quality-of-life impacts on caregivers of patients with mining-related lung cancer. Methods: This concurrent, embedded, mixed-methods study used individual in-depth qualitative interviews and the 36-item Short Form Health Survey (version 2: RAND Corporation, Santa Monica, CA, U.S.A.) quality-of-life measure with 8 caregivers of patients with suspected mining-related lung cancer who had worked in Sudbury or Elliot Lake (or both), and sometimes elsewhere. Individuals who assist workers in filing compensation claims were also interviewed in Sudbury and Elliot Lake. Interviews (n = 11) were transcribed and analyzed thematically. Results: Caregiver themes focused on the long time to, and the shock of, diagnosis and dealing with lung cancer; not much of a life for caregivers; strong views about potential cancer causes; concerns about financial impacts; compensation experiences and long time to compensation; and suggestions for additional support. Quality-of-life scores were below the norm for most measures. Individuals who assist workers in preparing claims were passionate about challenges in the compensation journey; the requirement for more and better family support; the need to focus on compensation compared with cost control; the need for better exposure monitoring, controls, resources, and research; and job challenges, barriers, and satisfaction. Conclusions: Caregivers expressed a need for more education about the compensation process and for greater support. Worker representatives required persistence, additional workplace monitoring and controls, additional research, and a focus on compensation compared with cost control. They also emphasized the need for more family support.

Detection of blood Gb3 deposits as a new tool for diagnosis and therapy monitoring in patients with classic Fabry disease.

BACKGROUND: The X-linked Fabry disease (FD) is a multiorgan disorder due to alpha-galactosidase A (α-GAL) deficiency with consequent lysosomal accumulation of globotriaosylceramide (Gb3). We established the immunocytochemical detection of Gb3 in blood cells of FD patients as a new method for FD diagnostics, follow-up and treatment control. METHODS: We enrolled 67 FD patients (37 men, 30 women) and 52 healthy controls (26 men, 26 women). PBMC were isolated from whole venous blood and 3x105 cells were immunoreacted with antibodies against CD77 as a marker for Gb3. Using fluorescence microscopy, the mean percentage of Gb3 positive PBMC was determined by an investigator blinded to subject allocation. As a second method, we qualitatively assessed Gb3 positive cells in blood smears. RESULTS: Gb3 deposits were unequivocally visible in PBMC and in blood smears. Men (P < 0.001) and women (P < 0.01) with classical FD had more Gb3-positive PBMC than healthy controls, whose samples only occasionally showed positive cells. The number of Gb3 positive PBMC was negatively correlated with α-GAL activity and positively correlated with plasma lyso-Gb3 levels. Only the PBMC Gb3 load but not plasma lyso-Gb3 reflected short- and long-term effects of enzyme replacement therapy (P < 0.01). CONCLUSIONS: Gb3 can be visualized in PBMC and blood smears and can be used as a novel marker for diagnostics, follow-up and treatment control in FD.

[Big data and deep learning in preventive and rehabilitation medicine]. / Big Data und maschinelles Lernen bei Prävention und Rehabilitation.

The digitalization in medicine has led to almost universal availability of information to different healthcare professionals and accelerated clinical pathways. Fast-track concepts and short hospital stays require intelligent and practicable systems in preventive and rehabilitation medicine. This includes optimization of movement analysis by innovative tools such as detectors sensing skin movements, portable feedback systems for monitoring, robot-assisted devices, and prevention programs based on reliable data. Finally, clinical structures are needed to exploit the maximal potential of artificial intelligence (AI) and deep learning. One example is the establishment of inter- and transdisciplinary professional teams such as a RehaBoard. In contrast to other cost-intensive disciplines such as oncology, the introduction of AI into rehabilitation orthopedics and trauma surgery with the support of cross-sectoral cooperation has great potential for performing well in patient benefit-orientated competition (value-based competition).

Insights into the role of androgen receptor in human testicular peritubular cells.

Contractile smooth muscle-like peritubular cells build the wall of seminiferous tubules in men. They are crucial for sperm transport and complement the functions of Sertoli cells by secreting factors, including glial cell line-derived neurotrophic factor. Previous studies revealed that they also secrete the chemokine C-X-C motif chemokine ligand 12 (CXCL12), which has known roles in spermatogenesis. Peritubular cells express the androgen receptor (AR), which is retained in isolated human testicular peritubular cells. We aimed to explore AR-regulated functions in human testicular peritubular cells. Bearing in mind that infertile men often have high aromatase activity, which may lower intratesticular androgen concentrations, an animal model for male infertility was studied. These mice display an age-dependent loss in spermatogenesis due to high aromatase activity. Human testicular peritubular cells were exposed to dihydrotestosterone or the antiandrogen flutamide. We studied AR, smooth muscle cell markers, glial cell line-derived neurotrophic factor and 15 secreted factors previously identified, including CXCL12. We used qPCR, Western blotting, ELISA or selected reaction monitoring (SRM). In the animal model for male infertility, we employed qPCR and immunohistochemistry. Dihydrotestosterone increased AR and flutamide prevented these actions. The smooth muscle cell markers calponin and smooth muscle actin were likewise increased, while cell size or cellular proliferation was not changed. Dihydrotestosterone did not increase glial cell line-derived neurotrophic factor or CXCL12 secretion but increased levels of serine proteinase inhibitor (SERPIN) E1. The animal model for male infertility with high aromatase activity showed reduced numbers of AR-immunoreactive testicular peritubular cells, suggesting that altered androgen and/or oestrogen levels could influence AR-mediated responses in peritubular cells. Androgens act on human testicular peritubular cells to enhance AR levels, their contractile phenotype and to modulate the secretion of some secreted factors. This study suggests that some aspects of human peritubular cell functions are regulated by androgens.

[Deep learning to support therapy decisions for intravitreal injections]. / Deep Learning zur Unterstützung der Therapieentscheidung bei intravitrealen Injektionen.

Significant progress has been made in artificial intelligence and computer vision research in recent years. Machine learning methods excel in a wide variety of tasks where sufficient data are available. We describe the application of a deep convolutional neural network for the prediction of treatment indication with anti-vascular endothelial growth factor (VEGF) medications based on central retinal optical coherence tomography (OCT) scans. The neural network classifier was trained with OCT images acquired during routine treatment at the University of Regensburg over the years 2008-2016. In over 95% of the cases the treatment indication was accurately predicted based on a singular OCT B scan without human intervention. Despite promising classification the results of deep learning techniques, should always be controlled by the treating physician because false classification can never be excluded due to the probabilistic nature of the method.

[Cavernomas of the central nervous system : Observational study of 111 patients]. / Kavernome des Zentralnervensystems : Verlaufsbeobachtung bei 111 Patienten.

PURPOSE: The prevalence of cavernomas (cavernous hemangioma) is 0.1-0.7%. Cavernomas are often found as an incidental finding within the framework of magnetic resonance imaging (MRI) examinations in mainly young and healthy patients. In the literature, the reported risk of hemorrhage varies greatly and is sometimes higher than that of aneurysms, which is surprising given that cavernomas are part of the low blood pressure system. After the diagnosis the medical practitioner and the patient have to decide on the further therapy, either surgical removal or the strategy of watchful waiting (conservative treatment). The aim of our study was to determine the frequency of bleeding of cavernomas and the consequences and to determine the satisfaction of patients with treatment. All these aspects should make the therapeutic decision easier for medical practitioners. MATERIAL AND METHODS: The study included all patients who were treated in the military hospital in Ulm during the period 2002-2012 and with the diagnosis of one or more cavernomas of the central nervous system (CNS) detected by MRI. This resulted in a total number of 111 patients. We recorded the epidemiological data and analyzed all cavernomas with respect to the location, size, treatment, side effects, etc. Furthermore, all included patients were sent a comprehensive questionnaire about symptoms, course of the disease and the quality of life. The response rate was 38%. All the collected data were analyzed with respect to the various aspects. RESULTS: Depending on the definition of a bleeding event of a cavernoma and selection of the observational period, the probability of a hemorrhage risk ranged from 1.3% to 5.9% per patient year. This relatively high proportion is, however, put into perspective by the mostly mild consequences of a bleeding event. Many cavernomas, which were detected as an incidental finding showed signs of previous bleeding but the patients remained free of symptoms. Additionally, there was no patient in this collective who suffered serious consequences due to a bleeding event. Of the patients with temporal cavernomas 45% had symptomatic epilepsy. The results of the patient survey were heterogeneous. Some patients stated that in retrospect they would not choose surgical treatment again. CONCLUSION: As a result of our findings we think it is important to critically look at the indications for surgical removal of cavernomas and special attention must be paid to informed consent of the patient. The frequent appearance of temporal cavernomas and their propensity to epileptic seizures is an essential aspect, which certainly influences the therapeutic decision. Although cavernomas are a venous malformation in the low blood pressure system, the determined frequency of hemorrhage was 5.9%, which was higher than expected but which is confirmed by other studies. Reports on severe sequelae of cavernoma bleeding are also rare in the literature, which relativizes the resulting danger of the relatively high probability of hemorrhage.

Unilateral sagittal split ramus osteotomy: an alternative for some cases of asymmetric mandibular prognathism.

The objective of this study was to propose a treatment protocol for patients with lateral prognathism based on the unilateral sagittal split ramus osteotomy (USSRO). This was a prospective study involving 31 patients with lateral prognathism, who required a bilateral sagittal split ramus osteotomy (BSSRO). Two groups were formed using the proposed protocol, with specific inclusion criteria for each group: BSSRO (n=17) and USSRO (n=14). Occlusal parameters (dental midline deviation, overbite, and overjet) were measured preoperatively (T0), at model surgery (T1), 1 month postoperative (T2), and 1year after surgery (T3) and compared. P-values of <0.05 were considered significant. No significant difference was found between the USSRO and BSSRO groups for all occlusal parameters (T0, T1, T2, and T3). In both groups, there was a significant difference between T0 and T1 and no significant difference between T1 and T2 or T1 and T3 in all of the occlusal parameters; the exception was overbite between T1 and T2 in the BSSRO group, which showed a significant difference. No patient in either group showed signs or symptoms of temporomandibular joint dysfunction at T0 or T3. USSRO was found to be a stable alternative in patients with asymmetric mandibular prognathism. At the same time, it reduced the operating time and morbidity when compared to BSSRO.

[Interventional radiology in the head and neck region]. / Interventionelle Radiologie im Kopf-Hals-Bereich.

In interventional neuroradiology, endovascular embolization represents an important and helpful tool in the treatment of multiple head and neck diseases. These interventional procedures may be performed with curative intent, to reduce the surgical risk within a multimodal treatment concept, or to improve or at least maintain a good quality of life within a palliative therapy concept. In addition to a good understanding of disease pathology, knowledge of vascular anatomy, including collateral vessels and dangerous extracranial-intracranial anastomoses, is essential for successful treatment, as is implementation of an established technique using appropriate material. Indications for endovascular embolization are i. otherwise unmanageable bleeding (caused by e. g., trauma, vascular malformation, or tumor), ii. reduction of perioperative bleeding by preoperative embolization in case of a hypervascularized tumor, iii. selective induction of tumor necrosis by palliative embolization to enhance local tumor control. Major complications such as stroke, loss of vision, and cranial nerve palsy are mostly due to a lack of preinterventional evaluation. Regarding neurological deficits, interventions within the supply region of the external carotid artery have a complication rate below 1%.

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells.

Changes in the wall of seminiferous tubules in men with impaired spermatogenesis imply sterile inflammation of the testis. We tested the hypothesis that the cells forming the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), orchestrate inflammatory events and that Toll like receptors (TLRs) and danger signals from the extracellular matrix (ECM) of this wall are involved. In cultured HTPCs we detected TLRs, including TLR2. A TLR-2 ligand (PAM) augmented interleukin 6 (IL-6), monocyte chemo-attractant protein-1 (MCP-1) and pentraxin 3 (PTX3) in HTPCs. The ECM-derived proteoglycan biglycan (BGN) is secreted by HTPCs and may be a TLR2-ligand at HTPCs. In support, recombinant human BGN increased PTX3, MCP-1 and IL-6 in HTPCs. Variable endogenous BGN levels in HTPCs derived from different men and differences in BGN levels in the tubular wall in infertile men were observed. In testes of a systemic mouse model for male infertility, testicular sterile inflammation and elevated estradiol (E2) levels, BGN was also elevated. Hence we studied the role of E2 in HTPCs and observed that E2 elevated the levels of BGN. The anti-estrogen ICI 182,780 blocked this action. We conclude that TLR2 and BGN contribute to sterile inflammation and infertility in man.

[Sympathetic ophthalmia : Therapy with steroid-free immunosuppressant azathioprine]. / Sympathische Ophthalmie : Therapie mit steroidsparendem Immunsuppressivum Azathioprin.

This article describes the case of a 48-year-old male patient who presented with persistent inflammation and deterioration of vision to a best corrected visual acuity (BCVA) of 0.6 in the only functioning left eye. The right eye had suffered a severe penetrating ocular trauma 6 months prior to presentation. After diagnosis of a sympathetic ophthalmia a high dosage corticosteroid therapy was initiated. Due to intolerance with decompensating diabetes an immunosuppressive therapy with azathioprine was initiated. This therapy resulted in stable clinical findings with an increase in BCVA to 0.9.

Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction.

Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. Microglial/macrophage activation was specifically associated with these restricted microdomains, as evidenced by rapid microglial process retraction, increased ameboid morphology, and escape of blood-borne Q-dot tracers that were internalized in microglial/macrophage cell bodies and phagosome-like compartments. Microdomains of cortical vascular disruption and microglial/macrophage activation were also associated with aberrant tight junction morphology that was more prominent after repetitive (3×) blast exposure. Repetitive, but not single, BOPs also caused TNFα elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuroinflammatory responses.

[Posttraumatic endophthalmitis : Complication following severe eye injury]. / Posttraumatische Endophthalmitis : Komplikation nach dem Kampf ums Auge.

BACKGROUND: Posttraumatic endophthalmitis is a rare but another extremely threatening complication for quality of vision, which has already been compromised by the trauma after perforating eye injuries. One of the substantial difficulties is the distinction between posttraumatic inflammation and development of a bacterial infection. METHODS: In a hospital-based study 149 consecutive cases of perforating ocular trauma with open injuries to the eye within a 5-year period were retrospectively investigated. The study included assessment of the relationship between the severity of the injury and the risk of posttraumatic endophthalmitis using the ocular trauma score (OTS), the diagnosis, the therapeutic management and the prognosis concerning visual outcome 1 year after the posttraumatic endophthalmitis. RESULTS: In this study posttraumatic endophthalmitis was observed in 8 out of 149 cases (5.4 %) after perforating ocular injuries. Severe injuries had a higher risk of this complication. In comparison to the clinical courses of non-postraumatic endophthalmitis, the visual outcome showed a tendency to be worse after an average of 18 ± 6 months (1.25 vs 1.0 logMAR). In all of the cases the posttraumatic endophthalmitis could be successfully treated with antibiotics and surgery and the already severely limited visual function due to the injury could at least be maintained in most cases. DISCUSSION: Due to the low case numbers statistical evidence of a clear benefit of treatment by a rapidly initiated and intensive individualized surgery following trauma and a pathogen-specific and operative therapy is not possible: nevertheless, such a comprehensive therapeutic approach to posttraumatic endophthalmitis is recommended.

The nuclear aryl hydocarbon receptor is involved in regulation of DNA repair and cell survival following treatment with ionizing radiation.

In the present study, we explored the role of the aryl hydrocarbon receptor (AhR) for γ-H2AX associated DNA repair in response to treatment with ionizing radiation. Ionizing radiation was able to stabilize AhR protein and to induce a nuclear translocation in a similar way as described for exposure to aromatic hydrocarbons. A comparable AhR protein stabilization was obtained by treatment with hydroxyl-nonenal-generated by radiation-induced lipid peroxidation. AhR knockdown resulted in significant radio-sensitization of both A549- and HaCaT cells. Under these conditions an increased amount of residual γ-H2AX foci and a delayed decline of γ-H2AX foci was observed. Knockdown of the co-activator ARNT, which is essential for transcriptional activation of AhR target genes, reduced AhR-dependent CYP1A expression in response to irradiation, but was without effect on the amount of residual γ-H2AX foci. Nuclear AhR was found in complex with γ-H2AX, DNA-PK, ATM and Lamin A. AhR and γ-H2AX form together nuclear foci, which disappear during DNA repair. Presence of nuclear AhR protein is associated with ATM activation and chromatin relaxation indicated by acetylation of histone H3. Taken together, we could show, that beyond the function as a transcription factor the nuclear AhR is involved in the regulation of DNA repair. Reduction of nuclear AhR inhibits DNA-double stand repair and radiosensitizes cells. First hints for its molecular mechanism suggest a role during ATM activation and chromatin relaxation, both essential for DNA repair.

Human testicular peritubular cells secrete pigment epithelium-derived factor (PEDF), which may be responsible for the avascularity of the seminiferous tubules.

Male fertility depends on spermatogenesis, which takes place in the seminiferous tubules of the testis. This compartment is devoid of blood vessels, which are however found in the wall of the seminiferous tubules. Our proteomic study using cultured human testicular peritubular cells (HTPCs) i.e. the cells, which form this wall, revealed that they constitutively secrete pigment epithelium-derived factor, PEDF, which is known to exert anti-angiogenic actions. Immunohistochemistry supports its presence in vivo, in the human tubular wall. Co-culture studies and analysis of cell migration patterns showed that human endothelial cells (HUVECs) are repulsed by HTPCs. The factor involved is likely PEDF, as a PEDF-antiserum blocked the repulsing action. Thus testicular peritubular cells, via PEDF, may prevent vascularization of human seminiferous tubules. Dihydrotestosterone (DHT) increased PEDF (qPCR) in HTPCs, however PEDF expression in the testis of a non-human primate occurs before puberty. Thus PEDF could be involved in the establishment of the avascular nature of seminiferous tubules and after puberty androgens may further reinforce this feature. Testicular microvessels and blood flow are known to contribute to the spermatogonial stem cell niche. Hence HTPCs via control of testicular microvessels may contribute to the regulation of spermatogonial stem cells, as well.

Predictive factors for intraocular pressure reduction after phacoemulsification in Swiss patients.

BACKGROUND: Phacoemulsification is known to induce postoperative intraocular pressure (IOP) reduction, the degree of which varies according to glaucoma subtype and race. The authors set out to investigate the effect of cataract surgery on IOP, in a Swiss Caucasian population, and identify ocular predictive factors. PATIENTS AND METHODS: 234 consecutive cases of 188 patients undergoing phacoemulsification between January 2011 and December 2012 were retrospectively reviewed and data collected. Exclusion criteria included acute angle closure, malignant glaucoma and pre-existing or subsequent glaucoma surgery. Pre- and post-operative visual acuity, IOP, gonioscopic findings, glaucoma medications, and laser treatments were recorded for eligible eyes. All eyes received the same postoperative regimen. Using multivariate analysis the predictive power of preoperative IOP, iridocorneal angle width, axial length on IOP reduction following phacoemulsification at months 3, 6 and 12 postoperatively were assessed. Eyes with narrow angles were compared against those with open angles. RESULTS: 172 eyes of 121 patients met the inclusion criteria; mean age was 70.3 years (SD±10.7 years), with 77 males. Preoperatively median IOP was 16 mmHg (range 9-32 mmHg), mean number of glaucoma medications was 1.2 (SD±1.1), median visual acuity was 0.28 LogMAR (range 0-2.3LogMar). At 3 months post-operatively mean IOP decreased to 14 mmHg (p<0.01) and remained statistically significantly reduced until 12 months, mean number of glaucoma medications was reduced to 1.0 and mean Snellen visual acuity increased to 0.8. Multivariate analysis revealed that pre-operative IOP and iridocorneal angle width (at 3 months) were significant predictive indicators of IOP reduction. At 12 months, IOP reduction was similar between open and narrow angle groups and total IOP reduction was no longer statistically significant. No intraoperative complications were recorded. CONCLUSIONS: Intraocular pressure reduction following phacoemulsification was greatest during the very early post-operative period, particularly in narrow angle patients. By one year, angle size was no longer predictive of IOP lowering, however pre-operative IOP and number of anti-glaucoma medications remained correlated with total IOP reduction.