Chronic, acute and protocol-dependent effects of exercise on psycho-physiological health during long-term isolation and confinement.

Exercise could prevent physical and psychological deteriorations, especially during pandemic times of lock-down scenarios and social isolation. But to meet both, the common exercise protocols require optimization based on holistic investigations and with respect to underlying processes. This study aimed to explore individual chronic and acute effects of continuous and interval running exercise on physical and cognitive performance, mood, and affect and underlying neurophysiological factors during a terrestrial simulated space mission. Six volunteers (three females) were isolated for 120 days. Accompanying exercise training consisted of a continuous and interval running protocol in a cross-over design. Incremental stage tests on a treadmill were done frequently to test physical performance. Actigraphy was used to monitor physical activity level. Cognitive performance, mood (MoodMeter®), affect (PANAS), brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular-endothelial growth factor (VEGF), and saliva cortisol were investigated prior to, four times during, and after isolation, pre- and post-exercise on two separate days, respectively. As a chronic effect, physical performance increased (and IGF-1 tended) in the course of isolation and training until the end of isolation. Subjective mood and affect state, as well as cognitive performance, basal BDNF and VEGF levels, were well-preserved across the intervention. No acute effects of exercise were detected, besides slower reaction time after exercise in two out of nine cognitive tests, testing sensorimotor speed and memory of complex figures. Consistently higher basal IGF-1 concentrations and faster reaction time in the psychomotor vigilance test were found for the continuous compared to the interval running protocol. The results suggest that 120 days of isolation and confinement can be undergone without cognitive and mental deteriorations. Regular, individual aerobic running training supporting physical fitness is hypothesized to play an important role in this regard. Continuous running exercise seems to trigger higher IGF-1 levels and vigilance compared to interval running. Systematic and prolonged investigations and larger sample size are required to follow up on exercise-protocol specific differences in order to optimize the exercise intervention for long-term psycho-physiological health and well-being.

Influence of pedestal diameter on mode instabilities in Yb/Ce/Al-doped fibers.

In this paper we present numerical and experimental results revealing that the mode instability threshold of highly Yb-doped, Ce/Al co-doped pedestal fibers is affected by the size of the index-increased pedestal structure surrounding the core. An alternative preparation technology for the realization of large mode area fibers with very large Al-doped silica pedestals is introduced. Three different pedestal fiber design iterations characterized by low photodarkening were manufactured and tested in counter-pumped amplifier setups. Up to 1.9 kW continuous-wave output power of near-diffraction-limited beam quality (M2 = 1.26) was achieved with an 18/200/420 µm fiber of very low NA = 0.042, limited only by the occurrence of mode instabilities.

Targeted gene sequencing and whole-exome sequencing in autopsied fetuses with prenatally diagnosed kidney anomalies.

Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next-generation sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in-house-designed kidney-gene panel. In families where candidate variants were not identified, whole-exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney-gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses-presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney-gene panel and additional variants were identified. Next-generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT-ROBO signaling is implicated in human bilateral kidney agenesis.

Application of open-path Fourier transform infrared spectroscopy for atmospheric monitoring of a CO2 back-production experiment at the Ketzin pilot site (Germany).

During a controlled "back-production experiment" in October 2014 at the Ketzin pilot site, formerly injected CO2 was retrieved from the storage formation and directly released to the atmosphere via a vent-off stack. Open-path Fourier transform infrared (OP FTIR) spectrometers, on-site meteorological parameter acquisition systems, and distributed CO2 point sensors monitored gas dispersion processes in the near-surface part of the atmospheric boundary layer. The test site provides a complex and challenging mosaic-like surface setting for atmospheric monitoring which can also be found at other storage sites. The main aims of the atmospheric monitoring of this experiment were (1) to quantify temporal and spatial variations in atmospheric CO2 concentrations around the emitting vent-off stack and (2) to test if and how atmospheric monitoring can cope with typical environmental and operational challenges. A low environmental risk was encountered during the whole CO2 back-production experiment. The study confirms that turbulent wind conditions favor atmospheric mixing processes and are responsible for rapid dilution of the released CO2 leading to decreased detectability at all sensors. In contrast, calm and extremely stable wind conditions (especially occurring during the night) caused an accumulation of gases in the near-ground atmospheric layer with the highest amplitudes in measured gas concentration. As an important benefit of OP FTIR spectroscopic measurements and their ability to detect multiple gas species simultaneously, emission sources could be identified to a much higher certainty. Moreover, even simulation models using simplified assumptions help to find suitable monitoring network designs and support data analysis for certain wind conditions in such a complex environment.

Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment.

PURPOSE: To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6 months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal electroretinography (mfERG) measurements. METHODS: Fifty eyes of 50 nAMD patients receiving intravitreal anti-VEGF treatment with either bevacizumab or ranibizumab and eight eyes of eight control subjects were included. Fixation stability measurements were performed with the Eye-Link eyetracking system and the retinal area in degrees2 (deg2) containing the 68 % most frequently used fixation points (RAF68) was calculated. MfERG P1 amplitude and implicit time were analyzed in six concentric rings and as a summed response. Patients were examined at baseline, 3 and 6 months. Four different mfERG recordings were performed for the control subjects to mimic an involuntary unstable fixation: normal central fixation, 2.4°, 4.8°, and 7.1° fixation instability. RESULTS: For control subjects, a fixation instability of 2.4° (corresponding to the central hexagon) did not reduce mfERG ring amplitudes significantly, whereas 4.8° and 7.1° fixation instability reduced the amplitudes significantly in rings 1 and 2 (p < 0.001) as well as in the peripheral rings in the 7.1° instability condition (p < 0.001). Fixation stability improved non-significantly for patients at 3 and 6 months. The size of the retinal area of fixation was at baseline, 3 and 6 months negatively correlated to visual acuity (VA) (rbaseline = -0.65, r3 months = -0.60, and r6 months = -0.66 respectively, p < 0.001) and mfERG amplitudes of the three innermost rings (rbaseline = -0.29, p = 0.042, r3 months = -0.43, p = 0.003 and r6 months = -0.31, p = 0.042). The VA cutoff for a fixation area less than 5 deg2 (approximately the central hexagon) was 65, 77, and 68 ETDRS letters (corresponding a maximal Snellen equivalent of 0.31) at baseline, 3 and 6 months, respectively. CONCLUSIONS: MfERG amplitudes in recordings of nAMD patients are at substantial risk of being reduced due to poor fixation as a large number of patients may use a fixation area of more than 5 deg2. Fixation monitoring during recording as well as interpretation of results should be performed with care, especially in patients with poor visual acuity.

The quantitative effect of antimicrobial usage in Danish pig farms on the abundance of antimicrobial resistance genes in slaughter pigs.

Research has long established the connection between antimicrobial use (AMU) and antimicrobial resistance (AMR) in production animals, and shown that the ceasing of AMU reduces AMR. Our previous study of Danish slaughter-pig production found a quantitative relationship between lifetime AMU and abundance of antimicrobial resistance genes (ARGs). This study aimed to generate further quantitative knowledge on how changes in AMU in farms influence the abundance of ARGs both with immediate effect and over time. The study included 83 farms that were visited from 1 to 5 times. From each visit, a pooled faecal sample was produced. The abundance of ARGs was obtained by metagenomics. We used two-level linear mixed models for estimating the effect of AMU on the abundance of ARGs against six antimicrobial classes. The lifetime AMU of each batch was calculated from usage during their three rearing periods; as piglets, weaners and slaughter pigs (rearing pathway). AMU at farm level was estimated as the mean lifetime AMU of the sampled batches from each farm. At batch level, AMU was measured as the deviation between the batch-specific lifetime AMU and the general mean lifetime AMU at the farm. For peroral tetracycline and macrolide use there was a significant quantitative linear effect on the abundance of ARGs in batches within individual farms, indicating an immediate effect of changed AMU from batch to batch within farms. These estimated effects between batches within farms were approximately 1/2-1/3 of the effect estimated between farms. For all antimicrobial classes, the effect of the mean farm-level AMU and the abundance of ARGs present in the faeces of slaughter pigs was significant. This effect was identified only for peroral use, except for lincosamides, where the effect was for parenteral use. The results also indicated that the abundance of ARGs against a specific antimicrobial class also increased by the peroral usage of one or several other antimicrobial classes, except for ARGs against beta-lactams. These effects were generally lower than the AMU effect of the specific antimicrobial class. Overall, the farm peroral mean lifetime AMU affected the abundance of ARGs at antimicrobial class level and abundance of ARGs of other classes. However, the difference of AMU of the slaughter-pig batches affected only the abundance of ARGs at the same antimicrobial class level in the same antimicrobial class. The results do not exclude that parenteral usage of antimicrobials may have an effect on the abundance of ARGs.

HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis.

OBJECTIVE: To reassess the effect of modafinil, a wakefulness-promoting artificial psychostimulant, on fatigue and neuropsychological measures in patients with multiple sclerosis. METHODS: Multiple sclerosis (MS) patients with a baseline score of ≥4 on the Fatigue Severity Scale (FSS) and an Expanded Disability Status Scale score <7 were eligible for the 8-week randomized, double-blind, placebo-controlled study. Modafinil was dosed up to 200 mg/day within 1 week. Assessments were performed at baseline and after 4 and 8 weeks. The primary outcome parameter was the mean change of the FSS mean score. Secondary outcome variables were other questionnaires covering fatigue, daytime sleepiness and sleep quality. Cognitive impairment was assessed by the oral version of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). RESULTS: The study included 121 MS patients. Dropout rate was 9%. Both treatment groups showed improvements through time. While mean FSS at 8 weeks showed a trend difference between groups in the intention-to-treat analysis, the primary endpoint was not met. Assessment of cognitive impairment by SDMT and PASAT showed contradictory results. All other secondary endpoints were not met. There was no major safety concern. CONCLUSIONS: In general, the study does not support modafinil as an effective treatment for MS fatigue. However, the study shows the need for new study designs and endpoints in MS fatigue studies.

A ferric chloride induced arterial injury model used as haemostatic effect model.

A number of experimental bleeding models have been applied to animal models of haemophilia in order to evaluate the acute haemostatic effect of procoagulant compounds. In contrast, in vivo thrombosis models (including the FeCl(3) induced injury model) have mainly been used to study antithrombotic pharmacological intervention. However, as there are limitations to existing bleeding models and as new recombinant FVIII, FIX, and FVIIa variants with increased and prolonged activity are generated there is an increasing need for new and optimized in vivo animal models for testing the efficacy of these haemostatic drug candidates. This led us to look at existing thrombosis models in a new perspective. We have studied the effect of a FeCl(3) induced arterial injury in both F8-KO and F9-KO mice using optimized conditions where exposure to FeCl(3) induces occlusion within 4.2 +/- 0.2 min in wild type mice with a normal coagulation system. In contrast, no occlusion was observed in haemophilic mice providing a therapeutic window in the model making it suitable for pharmacological testing of therapeutic intervention. We demonstrate that replacement therapy with a clinical relevant dose of rFVIII (Advate 20-80 U kg(-1)) and rFIX [(0.75 mg kg(-1) BeneFIX) approximately 50 IU kg(-1)] restored coagulation and normalized the time to occlusion following FeCl(3) induced injury in F8-KO mice and restored coagulation and nearly normalized the time to occlusion in F9-KO mice. In conclusion, we have demonstrated that under optimized conditions the FeCl(3) induced arterial injury model provides a therapeutic window that makes it an useful effect model for evaluation of the haemostatic potential of procoagulant drugs.

Increased performance of secondary clarifiers using dynamic distribution of minimum return sludge rates.

Most wastewater treatment plants have several secondary clarifiers or even more sets of clarifiers including several secondary clarifiers, and in practice it is a well known problem that equal distribution of the load to the single clarifier (or set of clarifiers) is very difficult-not to say impossible-to obtain. If the problem is neglected, quite a big percentage of the total clarifier capacity-measured as the max. allowed hydraulic load-can be lost. Further, return sludge rates are seldom controlled by any other means than as a (typically too high) percentage of the inlet to the wastewater treatment plant-giving a varying and too low suspended solids concentration in the return sludge, which again can lead to an unnecessary use of polymer in the pre-dewatering of the surplus sludge taken from the return sludge. A control of the return sludge rate divided into two parts - control of the total return sludge flow and control of how the total flow shall be distributed between the secondary clarifiers - is able to solve the mentioned problems. Finally, as shall be demonstrated on full scale wastewater treatment plants, a considerable increase of the hydraulic capacity of the treatment plants can be obtained.

Intubating laryngeal mask as a ventilatory device during percutaneous dilatational tracheostomy: a descriptive study.

BACKGROUND: We use an intubating laryngeal mask (ILM) in preference to an endotracheal tube (ETT) as the ventilatory device during percutaneous dilatational tracheostomy (PDT) to overcome potential problems such as difficult ventilation, accidental extubation, damage of the ETT or of the bronchoscope, and need for additional assistant to secure the airway. We report our experience with this method. METHODS: In this prospective observational study, PDT was performed using the ILM in 86 patients. The insertion of the ILM, the quality of ventilation, and the view of the tracheal puncture site were rated as: 'very good', 'good', 'difficult', and 'not possible with ILM'. RESULTS: The bronchoscope was not damaged during any case, and all PDTs were performed by two physicians, without the need for an additional assistant. PDTs with ILM were successful in 95% of the patients (n=82). The ratings were 'very good' or 'good' in 80% of cases with regards to ventilation, in 90% for identification of relevant structures and tracheal puncture site, and in 85% for the view inside the trachea during PDT. Tracheal re-intubation was required for inadequate ventilation with ILM in four patients. CONCLUSIONS: The advantages of this procedure were lack of damage to the bronchoscope, the need for two instead of three persons to perform the PDT, and the excellent view inside the trachea. We recommend the ILM as a standard device for ventilation during bronchoscope-guided PDT.

Modulation of the CO2 fixation in dinickel azacryptands.

While bimetallic azacryptands are known to selectively coordinate CO2, there is little knowledge on how different substitution patterns of the azacryptand cage structure influence CO2 coordination. Stopped-flow UV-vis spectroscopy, electrochemical analysis and DFT calculations were performed on a series of dinickel azacryptands and showed different rates of CO2 coordination to the complexes. We herein present data showing that the different flexibility of the azacryptands is directly responsible for the difference in the CO2 uptake capability of dinickel azacryptand complexes.

Bimetallic nickel complexes for selective CO2 carbon capture and sequestration.

Herein we report a dinickel azacryptand complex that enables fast, selective, and tight CO2 binding from air. Exploiting the affinity of the cavitand towards azides, CO2 release was observed. Despite the stability of the azido complex, UV irradiation under atmospheric conditions proved to be a suitable pathway for N3(-) replacement by CO2.

Effect of salts on membrane binding and activity of adipocyte phosphatidate phosphohydrolase.

Isosmotic replacement of sucrose in a low ionic strength homogenizing buffer (0.25 M sucrose/1 mM EDTA/1 mM Tris-HCl, pH 7.4) with KCl increased the microsomal and decreased the soluble phosphatidate phosphohydrolase (EC 3.1.3.4) activity of isolated rat fat cells. At 54 mM KCl the microsomal specific activity was increased 6-fold and the soluble activity was decreased to less than one-third. Binding of enzyme was promoted by KCl and NaCl when the once isolated soluble and microsomal fractions were recombined and incubated at 37 degrees C. Half-maximal binding occurred at about 17 mM salt and maximal binding at about 50 mM. The pH optimum of binding was 7.8 in 15 mM Hepes. MgCl2, CaCl2 and spermine prevented desorption of microsomal enzyme at mu molar levels and maximal effects were observed at concentrations below the 1 mM level. At maximum, however, the prevention of desorption was less by these salts than it was by KCl. MgCl2 and spermine also interfered with the effect of KCl. Moderate salt-induced loading of microsomes with the phosphohydrolase (specific activity increased 3.5-fold) increased their ability to incorporate 14C into triacylglycerol from sn-[U-14C]glycerol 3-phosphate while a high loading (specific activity increased 6-fold) had no effect or even suppressed it. The results are discussed in relation to a role of translocation of phosphatidate phosphohydrolase in glyceride biosynthesis and its control.

Soluble rat adipocyte phosphatidate phosphatase activity: characterization and effects of fasting and various lipids.

Phosphatidate phosphatase (phosphatidate phosphohydrolase, EC 3.1.3.4) was present at very high specific activity in the soluble fraction of isolated rat adipocytes. Using phosphatidate in aqueous dispersion 90% of its hydrolysis depended on the presence of Mg2+. Mg2+ appeared to almost saturate the enzyme at 20-40 mM with no indication of an optimum. The substrate concentration was optimum at 1.2 mM and the pH at 6.8. Initial rates were linear for only 4-5 min at optimum conditions. Increasing inhibition occurred at high phosphatidate concentrations. At optimum conditions acid or alkaline phosphatase activity was not measurable. The Mg2+-dependent activity was enhanced by 3-sn-phophatidylcholine and inhibited by albumin, 3-sn-phosphatidyletanolamine, 3-sn-phosphatidylinositol, diacylglycerol, oleoyl-CoA, and oleate. Oleoyl-CoA was the most potent "effector". Fasting for 24, 48 and 72 h decreased the activity both relative to protein and to DNA. The activity thus decreased to about one-third of that of the fed rat during 72 h of fasting. The effects of Mg2+, various lipids, and fasting may indicate that some form of control of glyceride synthesis can be exerted through the soluble phosphatidate phosphatase.

[Cortical reorganization in children with connatal spastic hemiparesis -- a functional magnetic resonance imaging (FMRI) study]. / Kortikale Reorganisation bei Kindern mit konnataler spastischer Hemiparese -- eine funktionelle Magnetresonanztomographie-(fMRT-)Studie.

PURPOSE: We applied fMRI to investigate atypical cortical activation in patients with connatal spastic hemiparesis using voluntary movements of the hand, foot, and tongue. The relation between the findings from fMRI and the motor dysfunction was examined. MATERIALS AND METHODS: 11 patients with connatal spastic hemiparesis were studied. Eight of these patients had periventricular leukomalacia (PVL), and three patients had cortical-subcortical lesions. To evaluate the severity of motor impairment tests for the upper and lower limb were performed. fMRI data were obtained in a block design using hand, foot, and tongue movements. As a control group, 14 healthy volunteers were examined with the fMRI protocol. RESULTS: A laterally cortical representation of the paretic foot was found in three patients with PVL. In patients with cortical-subcortical lesions, tongue movements were associated with cortical activation restricted to the unaffected hemisphere. Movements of the paretic limb showed more ipsilateral activation in patients with PVL than in patients with cortical-subcortical lesions. CONCLUSION: Different types of structural damage such as PVL and cortical-subcortical lesions show differences in fMRI examination.

Is one 60 degrees fundus photograph sufficient for screening of proliferative diabetic retinopathy?

OBJECTIVE: To compare one 60 degrees fundus photograph to seven field stereo fundus photographs in identifying proliferative diabetic retinopathy. RESEARCH DESIGN AND METHODS: A total of 44 eyes in 23 patients with moderate/severe nonproliferative diabetic retinopathy were included. Evaluation of each eye was based on one 60 degrees fundus photograph. Eyes were re-examined using seven field 30 degrees stereo fundus photographs according to the protocol of the Early Treatment Diabetic Retinopathy Study, and the photographs were examined independently by three ophthalmologists to identify retinal neovascular lesions. In addition, fluorescein angiography was performed in all patients to verify the presence of the lesions. RESULTS: In four eyes of three patients (11.1% of eyes) evaluated based on seven field stereo photographs, retinal neovascularization was found. This condition was not found on examination of 60 degrees fundus photographs. CONCLUSIONS: Examination of one 60 degrees fundus photograph was found to be insufficient as a screening procedure in patients with moderate/severe nonproliferative diabetic retinopathy.

Uso de bastones contralaterales en artrosis de rodilla / Contralateral canes for knee osteoarthritis

INTRODUCCIÓN La artrosis de rodilla es un problema de salud relevante dada su alta prevalencia y discapacidad asociada. Dentro de las alternativas de manejo no farmacológico se ha planteado el uso de bastones, sin embargo no existe consenso en la literatura respecto a su indicación. MÉTODOS Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos tres revisiones sistemáticas que en conjunto incluyeron cuatro estudios primarios, de los cuales, uno es ensayo aleatorizado. Concluimos que el uso de bastón contralateral en pacientes con artrosis de rodilla probablemente disminuye el dolor. Además, podría aumentar levemente la funcionalidad, pero la certeza de la evidencia es baja.

INTRODUCTION Knee osteoarthritis is a relevant health problem given its high prevalence and associated disability. Within the non-pharmacological management alternatives, the use of canes has been proposed, however, there is no consensus in the literature regarding its indication. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified three systematic reviews including four studies overall, of which one was randomized trials. We conclude that the use of a contralateral cane in patients with knee osteoarthritis probably reduces pain. In addition, it could slightly increase function, but the certainty of the evidence is low.

Extracellular pH in the rat brain during hypoglycemic coma and recovery.

It has previously been shown that hypoglycemic coma is accompanied by marked energy failure and by loss of cellular ionic homeostasis. The general proposal is that shortage of carbohydrate substrate prevents lactic acid formation and thereby acidosis during hypoglycemic coma. The objective of the present study was to explore whether rapid downhill ion fluxes, known to occur during coma, are accompanied by changes in extra- and/or intracellular pH (pHe and/or pHi), and how these relate to the de- and repolarization of cellular membranes. Cortical pHe was recorded by microelectrodes in insulin-injected rats subjected to 30 min of hypoglycemic coma, with cellular membrane depolarization. Some rats were allowed up to 180 min of recovery after glucose infusion and membrane repolarization. Arterial blood gases and physiological parameters were monitored to maintain normotension, normoxia, normocapnia, and normal plasma pH. Following depolarization during hypoglycemia, a prompt, rapidly reversible alkaline pHe shift of about 0.1 units was observed in 37/43 rats. Immediately thereafter, all rats showed an acid pH shift of about 0.2 units. This shift developed during the first minute, and pHe remained at that level until repolarization was induced. Following repolarization, there was an additional, rapid, further lowering of pHe by about 0.05 units, followed by a more prolonged decrease in pHe that was maximal at 90 min of recovery (delta pHe of approximately -0.4 units). The pHe then slowly normalized but was still decreased (-0.18 pH units) after 180 min when the experiment was terminated. The calculated pHi showed no major alterations during hypoglycemic coma or after membrane repolarization following glucose administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of terminalis, olfactory, trigeminal and perivascular nerves in the rat nasal septum.

The innervation of the nasal septum and around the olfactory bulb has been investigated in rats by means of whole-mount preparations and histological sections. Silver staining, OsO4 staining, PAS staining, cholinesterase reaction and fluorescence for catecholamine-containing nerves were used. The nervus terminalis forms on the medial side of the olfactory bulb a ganglionated plexus, from which branches are given off which course peripherally with the vomeronasal nerves. From a dorsal part of the terminalis nerve plexus an anterior branch is given off which runs along the anterior ethmoidal nerve to the nasal vestibule where it connects with a group of ganglia. The peripheral branches of the nerve run from here along two epithelial cristae formed histologically like dermal papillae. Ventrally in the respiratory region at the junction of the nasal cavity and the nasopharynx is a 1 times 2 mm area with olfactory epithelium, glands of Bowman and an independent innervation from the olfactory bulb. This is the so-called septal olfactory organ. Trigeminal nerves form a plexus in the respiratory region and in the vestibule, but do not supply the olfactory region. Catecholamine-containing and cholinesterase-positive nerves run along the meningeal arteries on the cribriform plate and accompany their branches to the vascular plexus in the olfactory and respiratory regions. Double innervation is found not only of this vascular plexus but of the venous sinuses in the swell bodies of the vestibule. The glands of the nose are not surrounded by catecholamine-containing nerves.

Cellular mechanisms underlying differential rejection of sequential heart and lung allografts in rats.

As the simultaneous transplantation of two or more organs into a single recipient has become increasingly common, asynchronous allograft rejection has become an important clinical problem. To investigate the cellular and molecular mechanisms underlying differential organ rejection, we developed a rat model in which heart and lung allografts were transplanted sequentially. Heterotopic heart allografts transplanted into DA recipients from PVG donors survived indefinitely if the recipients were given a short course of rabbit antirat thymocyte globulin or cyclosporine at the time of transplantation. In contrast, orthotopic left lungs transplanted under the same conditions were rejected in ATG-treated recipients and accepted in most CsA-treated recipients. These animals were then given a second organ allograft from the same strain or a third party to assess whether they exhibited donor specific tolerance and whether the acceptance or rejection of the first allograft would influence the survival of the second transplant. Animals tolerized to a heart allograft with ATG rejected an orthotopic lung transplant from the same strain as the original allograft, whereas recipients treated with CsA at the time of their heart transplant accepted a subsequent lung graft. Surprisingly, animals treated with either ATG or CsA that had rejected a lung allograft accepted a subsequent heart transplant. Using limiting dilution analysis and adoptive transfer studies, we found that some recipients had developed suppressor cells while others demonstrated anergy. We conclude that major histocompatibility complex antigens as well as other antigens are involved in the differential rejection of heart and lung allografts.