0000000000142266
AUTHOR
Tanja Wolloscheck
Impact of single-dose application of TGF-β, copper peptide, stanozolol and ascorbic acid in hydrogel on midline laparatomy wound healing in a diabetic mouse model.
Despite numerous advances and improvements in surgical techniques the incidence of incisional hernias after laparotomy remains high. The aim of this study was to investigate possible effects of single application of ascorbic acid, stanozolol, a synthetic anabolic steroid, copper peptide and transforming growth factor-β (TGF-β) on laparotomy wound healing in an incisional wound model in diabetic mice. After diabetes induction with streptozotozin in Balb-c mice, midline laparatomies were carried out. Closure of the linea alba was followed by single-dose application of the agents dissolved in a hydrogel before skin closure. The functional outcome was assessed in terms of maximum tensile streng…
Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice
Growth factors and/or angiogenic factors are supposed to improve wound healing. The aim of our study was to evaluate the effects of subcutaneous pretreatment with combinatory proangiogenic factors on wound closure, mechan - ical properties, vessel density and morphology. Twenty-eight Balb/c mice were divided equally into two groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg) and P dGF (3.5 µg) was administered subcutaneously 3, 5 and 7 days to 14 mice before full thickness skin punch biopsy wounding, whereas 14 control animals received three injections of 0.2 ml saline solution. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after complete wound closure. Comp…
Transcriptional analysis of rat photoreceptor cells reveals daily regulation of genes important for visual signaling and light damage susceptibility.
Photoreceptor cells face the challenge of adjusting their function and, possibly, their susceptibility to light damage to the marked daily changes in ambient light intensity. To achieve a better understanding of photoreceptor adaptation at the transcriptional level, this study aimed to identify genes which are under daily regulation in photoreceptor cells using microarray analysis and quantitative PCR. Included in the gene set obtained were a number of genes which up until now have not been shown to be expressed in photoreceptor cells, such as Atf3 (activating transcription factor 3) and Pde8a (phosphodiesterase 8A), and others with a known impact on phototransduction and/or photoreceptor s…
Priming with a Combination of Proangiogenic Growth Factors Enhances Wound Healing in Streptozotocin-Induced Diabetes in Mice
<i>Background:</i> Numerous proangiogenic growth factors have been shown to improve impaired wound healing. This study evaluated the effects of subcutaneous pretreatment with a combination of proangiogenic growth factors on wound closure, mechanical properties, vessel density, and morphology. <i>Methods:</i> Thirty-six Balb/c mice with streptozotocin-induced diabetes were divided into 3 groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg), and PDGF (3.5 µg) was administered subcutaneously 3, 5, and 7 days prior to wounding in the first group, whereas the second group received three doses of 3.5 µg PDGF. Wound sizes were assessed daily and the repaired tissues were harv…
Forces and deformations of the abdominal wall—A mechanical and geometrical approach to the linea alba
Force-elongation responses of the human abdominal wall in the linea alba region were determined by tensile tests in which the linea alba was seen to exhibit a nonlinear elastic, anisotropic behavior as is frequently observed in soft biological tissues. In addition, the geometry of the abdominal wall was determined, based on MRI data. The geometry can be specified by principal radii of curvature in longitudinal of approximately 470 mm and in the transverse direction of about 200 mm. The determined radii agree with values found in other studies. Mechanical stresses, deformations and abdominal pressures for load cases above 6% elongation can be related using Laplace's formula and our constitut…
Transcriptional regulation of nucleoredoxin-like genes takes place on a daily basis in the retina and pineal gland of rats.
AbstractThe nucleoredoxin-like gene Nxnl1 (Txnl6) and its paralogue Nxnl2 encode the rod-derived cone viability factors (RdCVF and RdCVF2), which increase the resistance to photooxidative damage and have therapeutic potential for the survival of cones in retinitis pigmentosa. In this study, the transcription of Nxnl genes was investigated as a function of the day/night cycle in rats. The transcript levels of Nxnl1 and Nxnl2 were seen to display daily rhythms with steadily increasing values during the light phase and peak expression around dark onset in preparations of whole retina, photoreceptor cells and—but only in regard to Nxnl1—in photoreceptor-related pinealocytes. The cycling of Nxnl…
Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia
This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O(2)) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced…
Vessel painting of the microcirculation using fluorescent lipophilic tracers
Flexible approaches to defining microvessel morphometry are useful in the study of both acute and chronic structural changes of the microcirculation. In this report, we examined the utility of the intravascular infusion of lipophilic carbocyanine tracers in the structural assessment of the retina, skin, lung, and colon microcirculation. The microvessel labeling technique, here termed fluorescent vessel painting, involved the intravascular injection of sulfonated lipophilic carbocyanine tracers. The utility of vessel painting in morphometry was assessed using morphometric comparisons with corrosion casting and 2-dimensional and 3-dimensional scanning electron microscopy. The comparisons demo…
The murine bronchopulmonary microcirculation in hapten-induced inflammation
ObjectiveThe clinical observation of central bronchial artery hypertrophy in chronic lung inflammation suggests the possibility that the bronchial circulation may also participate in adaptive responses in peripheral lung inflammation.MethodsTo investigate the potential role of the bronchial microcirculation in peripheral lung inflammation, we developed a murine model of lung inflammation using the intratracheal instillation of the peptide-hapten trinitrophenol in presensitized mice.ResultsClinical parameters indicated a peak inflammatory response at 96 hours. Similarly, gross and microscopic evidence of inflammation was observed 96 hours after antigen instillation. Using a forced oscillatio…
Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells.
The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy-one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i.e. carnitine palmitoyltransferase-1α (Cpt-1α) and medium chain acyl-CoA dehydrogenase (A…
Inflammation-responsive focal constrictors in the mouse ear microcirculation
In many capillary exchange beds, blood flow is locally regulated by precapillary sphincter-like activity. In this study, we used intravascular tracers and scanning electron microscopy to investigate precapillary blood flow regulation in the mouse ear. Gelatin ink injections of the normal mouse ear demonstrated 6.8 +/- 2.3 axial vessels with a cutoff of detectable tracer in the early branches: 19 +/- 11 focal constrictions were observed along the 1st to 5th order branches of the axial vessels. A perfusion tracer consisting of biotinylated anti-endothelial lectins (Ricinus Communis Agglutin, Lycopersicon Esculentum and Griffonia Simplicifolia) was circulated for 30 min under physiological con…
Murine Microvideo Endoscopy of the Colonic Microcirculation
Natural orifice endoscopy in small animal models has been limited in the past by instrument size and optical performance. In this report, we investigate the feasibility of using a recently developed microvideo endoscopy system to evaluate the colon microcirculation. Using a murine model of acute colitis, microvideo endoscopy was useful in mapping the topography of inflammation as well as identifying relevant structures in the microcirculation. We conclude that natural orifice endoscopy is a useful method for the minimally invasive longitudinal assessment of the colonic mucosal microcirculation.
Möglichkeiten und Grenzen der Mikrogefäßdarstellung
Vessel systems and the microvascular unit may be studied by a variety of morphological techniques which enable improved structure-function analyses. Two-dimensional light and electron microscopic sectioning techniques with and without specific markers are complemented by 3D vascularisation and perfusion study techniques. Static ex vivo modalities still prevail, however, the future will be dominated by intravital high-resolution techniques.
Aortenklappenstrukturen als Orientierungshilfe zum Auffinden der Koronararterienabgänge in der transthorakalen Echokardiographie
Die Koronararterienabgange werden gelegentlich bei der echokardiographischen Untersuchung mit erfasst. Es fragte sich, ob diese Modalitat als nicht invasive Screeninguntersuchung genutzt werden kann. Voraussetzung hierfur ist eine sichere und reproduzierbare Erfassung der Koronararterienabgange. Patienten und Methode: Vor diesem Hintergrund wurde an 20 anatomischen Praparaten morphometrisch und an 50 Patienten einer kardiologischen Praxis mit transthorakalem Ultraschall die Abgangstopographie ausgemessen. Ergebnisse: Die Koronarostien lagen konstant exzentrisch im Sinus in Richtung des akoronaren Sinus verschoben. Der Abstand des linken Koronararterienostiums von der Kommissur zwischen Valv…
The Retinal Clock Drives the Expression ofKcnv2, a Channel Essential for Visual Function and Cone Survival
PURPOSE The gene Kcnv2 codes for the voltage-gated potassium channel subunit Kv8.2, which can coassemble with Kv2.1 subfamily members to constitute functional voltage-gated potassium channels. Mutations in the Kcnv2 gene result in a retinal disorder designated "cone dystrophy with supernormal rod response (CDSRR)," revealing that Kcnv2 is essential for visual processing and cone survival. The aim of this study was to determine whether expression of Kcnv2 and Kv2.1 is under circadian regulation and may thus contribute to the clock-driven adjustment of photoreceptor function. METHODS Expression of the genes was recorded in preparations of the whole retina and microdissected retinal neurons by…
Maximum forces acting on the abdominal wall: Experimental validation of a theoretical modeling in a human cadaver study
Incisional hernias following median laparotomy have a high incidence and recurrence rate after repair, so that a better understanding of the linea alba biomechanics is desirable. The mechanical stress exerted on the linea alba in living humans is primarily generated by the musculature. In this human cadaver study, intraabdominal pressure was simulated by insertion of a balloon that was increasingly filled to maximal pressures of 200 mbar. The related forces acting transversely on the linea alba at maximum pressure were found to be between 41.6 and 52.2 N/cm (mean = 45.9 N/cm), which is in agreement with a recent modeling of the related forces.
Daily Profile in Melanopsin Transcripts Depends on Seasonal Lighting Conditions in the Rat Retina
The retinal photopigment melanopsin (Opn4) mediates photoentrainment of the circadian system. In the present study, seasonal regulation of the melanopsin gene was investigated in comparison with the arylalkylamine N-acetyltransferase (AA-NAT) gene as an indicator of retinal pacemaker output. For this purpose, the daily profiles in the amount of melanopsin mRNA and AA-NAT mRNA were monitored under 8 : 16 h light/dark, 12 : 12 h light/dark and 16 : 8 h light/dark photoperiods using real-time polymerase chain reaction analysis. We found that, under all of the lighting regimes, melanopsin and AA-NAT expression oscillated with a peak around dark onset and the middle of the dark phase, respective…
Innervation der subperitonealen Beckenetage: Möglichkeiten zur Optimierung der Rektumchirurgie
Einleitung: Bei totaler mesorektaler Exzision (TME) soll die Rate postoperativer urogenitaler Funktionsstorungen durch genauere topographische Kenntnisse von Faszien- und Nervenverlaufen weiter abgesenkt werden. Methodik: An 10 anatomischen Korperspenden wurden makroskopische Praparationen, schnittanatomische Studien, histologische und immunhistochemische Untersuchungen sowie Morphometrien durchgefuhrt. Es wurden Faszienverhaltnisse und Nervenverlaufe analysiert. Ergebnisse: Die neurovaskularen Bundel zeigen als Auslaufer des Plexus hypo gastricus inferior die Hochste Dichte von Nervengewebe. Am lateralen Rand der Denonvilliers-Faszie treten sie unter der Fascia pelvis parietalis hervor. Za…
Unique clockwork in photoreceptor of rat
In mammals, the retina contains a clock system that oscillates independently of the master clock in the suprachiasmatic nucleus and allows the retina to anticipate and to adapt to the sustained daily changes in ambient illumination. Using a combination of laser capture micro-dissection and quantitative PCR in the present study, the clockwork of mammalian photoreceptors has been recorded. The transcript amounts of the core clock genes Clock, Bmal1, Period1 (Per1), Per3, Cryptochrome2, and Casein kinase Ie in photoreceptors of rat retina have been found to undergo daily changes. Clock and Bmal1 peak with Per1 and Per3 around dark onset, whereas Casein kinase Ie and Cryptochrome2 peak at night…
Structural adaptations in the murine colon microcirculation associated with hapten-induced inflammation
Objectives: Blood flowing across the vascular endothelium creates wall shear stress, dependent on flow velocity and vessel geometry, that tends to disrupt lymphocyte-endothelial cell adhesion. To identify structural adaptations during acute colitis that may facilitate transmigration, we investigated the microcirculation in a murine model of acute colitis. Methods: In trinitrobenzenesulfonic acid (TNBS)- induced acute colitis, the infiltrating cells and colonic microcirculation was investigated by cellular topographic mapping as well as corrosion casting and 3- dimensional (3D) scanning electron microscopy. Colonic blood velocimetry was performed using intravital microscopy. Results: Clinica…
Phosphodiesterase 10A in the Rat Pineal Gland: Localization, Daily and Seasonal Regulation of Expression and Influence on Signal Transduction
The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606–7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master cloc…
Photoreceptor cells display a daily rhythm in the orphan receptor Esrrβ
Purpose Nuclear orphan receptors are critical for the development and long-term survival of photoreceptor cells. In the present study, the expression of the nuclear orphan receptor Esrrβ—a transcriptional regulator of energy metabolism that protects rod photoreceptors from dystrophy—was tested under daily regulation in the retina and photoreceptor cells. Methods The daily transcript and protein amount profiles were recorded in preparations of the whole retina and microdissected photoreceptor cells using quantitative PCR (qPCR) and western blot analysis. Results Esrrβ displayed a daily rhythm with elevated values at night in the whole retina and enriched photoreceptor cells. Daily regulation…
Resection of the mesopancreas (RMP): a new surgical classification of a known anatomical space
Abstract Background Prognosis after surgical therapy for pancreatic cancer is poor and has been attributed to early lymph node involvement as well as to a strong tendency of cancer cells to infiltrate into the retropancreatic tissue and to spread along the peripancreatic neural plexuses. The objective of our study was to classify the anatomical-surgical layer of the mesopancreas and to describe the surgical principles relevant for resection of the mesopancreas (RMP). Immunohistochemical investigation of the mesopancreatic-perineural lymphogenic structures was carried out with the purpose of identifying possible routes of metastatic spread. Methods Resection of the mesopancreas (RMP) was per…
Pgc-1α and Nr4a1 Are Target Genes of Circadian Melatonin and Dopamine Release in Murine Retina
Purpose The neurohormones melatonin and dopamine mediate clock-dependent/circadian regulation of inner retinal neurons and photoreceptor cells and in this way promote their functional adaptation to time of day and their survival. To fulfill this function they act on melatonin receptor type 1 (MT1 receptors) and dopamine D4 receptors (D4 receptors), respectively. The aim of the present study was to screen transcriptional regulators important for retinal physiology and/or pathology (Dbp, Egr-1, Fos, Nr1d1, Nr2e3, Nr4a1, Pgc-1α, Rorβ) for circadian regulation and dependence on melatonin signaling/MT1 receptors or dopamine signaling/D4 receptors. Methods This was done by gene profiling using qu…
Phosphodiesterase10A: abundance and circadian regulation in the retina and photoreceptor of the rat.
Phosphodiesterase10A (PDE10A) is a dual specific cyclic nucleotide phosphodiesterase that is specifically enriched in striatum and which has gained attention as a therapeutic target for psychiatric disorders. The present study shows that PDE10A is also highly expressed in retinal neurons including photoreceptors. The levels of PDE10A transcript and protein display daily rhythms which could be seen in preparations of the whole retina. Corresponding changes in PDE10A mRNA were seen in photoreceptors isolated using laser microdissection. This suggests that the expressional control of the photoreceptor Pde10a gene contributes to the observed cyclicity in the amount of retinal PDE10A. The daily …