Parameters predicting COVID-19-induced myocardial injury and mortality.

Clinical manifestations of COVID-19 affect many organs, including the heart. Cardiovascular disease is a dominant comorbidity and prognostic factors predicting risk for critical courses are highly needed. Moreover, immunomechanisms underlying COVID-induced myocardial damage are poorly understood. OBJECTIVE: To elucidate prognostic markers to identify patients at risk. RESULTS: Only patients with pericardial effusion (PE) developed a severe disease course, and those who died could be identified by a high CD8/Treg/monocyte ratio. Ten out of 19 COVID-19 patients presented with PE, 7 (78%) of these had elevated APACHE-II mortality risk-score, requiring mechanical ventilation. At admission, PE patients showed signs of systemic and cardiac inflammation in NMR and impaired cardiac function as detected by transthoracic echocardiography (TTE), whereas parameters of myocardial injury e.g. high sensitive troponin-t (hs-TnT) were not yet increased. During the course of disease, hs-TnT rose in 8 of the PE-patients above 16 ng/l, 7 had to undergo ventilatory therapy and 4 of them died. FACS at admission showed in PE patients elevated frequencies of CD3+CD8+ T cells among all CD3+ T-cells, and lower frequencies of Tregs and CD14+HLA-DR+-monocytes. A high CD8/Treg/monocyte ratio predicted a severe disease course in PE patients, and was associated with high serum levels of antiviral cytokines. By contrast, patients without PE and PE patients with a low CD8/Treg/monocyte ratio neither had to be intubated, nor died. CONCLUSIONS: PE predicts cardiac injury in COVID-19 patients. Therefore, TTE should be performed at admission. Immunological parameters for dysfunctional antiviral immunity, such as the CD8/Treg/monocyte ratio used here, supports risk assessment by predicting poor prognosis.

The surface composition of charon: tentative identification of water ice.

The 3 March 1987 Charon occultation by Pluto was observed in the infrared at 1.5, 1.7, 2.0, and 2.35 micrometers. Subtraction of fluxes measured between second and third contacts from measurements made before and after the event has yielded individual spectral signatures for each body at these wavelengths. Charon's surface appears depleted in methane relative to Pluto. Constancy of flux at 2.0 micrometers throughout the event shows that Charon is effectively black at this wavelength, which is centered on a very strong water absorption band. Thus, the measurements suggest the existence of water ice on Pluto's moon.

Infrared Astronomy After IRAS.

The 250,000 sources in the recently issued Infrared Astronomy Satellite (IRAS) all-sky infrared catalog are a challenge to astronomy. Many of these sources will be studied with existing and planned ground-based and airborne telescopes, but many others can no longer even be detected now that IRAS has ceased to operate. As anticipated by advisory panels of the National Academy of Sciences for a decade, study of the IRAS sources will require the Space Infrared Telescope Facility (SIRTF), a cooled, pointed telescope in space. This instrument may be the key to our understanding of cosmic birth-the formation of planets, stars, galaxies, active galactic nuclei, and quasars. Compared with IRAS and existing telescopes, SIRTF's power derives from a thousandfold gain in sensitivity over five octaves of the spectrum.

The NASA Spitzer Space Telescope.

The National Aeronautics and Space Administration's Spitzer Space Telescope (formerly the Space Infrared Telescope Facility) is the fourth and final facility in the Great Observatories Program, joining Hubble Space Telescope (1990), the Compton Gamma-Ray Observatory (1991-2000), and the Chandra X-Ray Observatory (1999). Spitzer, with a sensitivity that is almost three orders of magnitude greater than that of any previous ground-based and space-based infrared observatory, is expected to revolutionize our understanding of the creation of the universe, the formation and evolution of primitive galaxies, the origin of stars and planets, and the chemical evolution of the universe. This review presents a brief overview of the scientific objectives and history of infrared astronomy. We discuss Spitzer's expected role in infrared astronomy for the new millennium. We describe pertinent details of the design, construction, launch, in-orbit checkout, and operations of the observatory and summarize some science highlights from the first two and a half years of Spitzer operations. More information about Spitzer can be found at http://spitzer.caltech.edu/.

Necrotizing effects of kainic acid on neurons in the pigeon brain: histological observations.

The neurotoxin kainic acid (KA) has been shown to destroy neurons in the pigeon paleostriatal complex (PC), the avian analogue of the caudato-putamen and globus pallidus. In this earlier study the movement disorders in pigeons were strikingly similar to those reported by others in rats following intracerebral injection of KA into the corpus striatum. The toxic influences of KA on other parts of the pigeon brain have not been described. Therefore, KA was injected into areas of the telencephalon, diencephalon, mesencephalon and cerebellum. Areas sensitive to KA showed a marked cell loss and the neuropil exhibited spaces that contained fragments of necrotic neurons. The injection sites were invaded by glia and granulocytes. Kainic acid had a local necrotizing effect; for example, it destroys neurons in the PC, nucleus rotundus, nucleus spiriformis lateralis, nucleus ruber and neurons of the cerebellar cortex. An apparent long-distance effect of KA was also observed, since intracerebral injections of KA into the PC was followed by cell loss in the ipsilateral nucleus of the ansa lenticularis. Kainic acid has proved to be a potent neurotoxin with a pronounced necrotizing effect upon neurons in the pigeon brain.

Presence and development of ependymal cells in primary tissue cultures derived from embryonic rat cerebral cortex.

Using indirect immunohistochemistry, a secondary antibody was detected in a commercial preparation of antiserum against vasoactive intestinal polypeptide. The secondary antibody selectively stained ependymal cells during the first 3 weeks in vitro in cultures of dissociated cerebral cortical tissue from rat. This staining provided a convenient mechanism for investigating the development and properties of these cells in cultures. The overall level of immunofluorescent staining during the initial 3-week time period appeared to directly reflect the proliferation and development of ependymal cells. Fluorescent staining was initially detected in cells which appeared to correspond to matrix cells or progenitor cells from the ependyma. These cells underwent rapid cell division, as evidenced by distinct morphological stages, to yield daughter cells which were the precursors of mature ependymal cells. Three different morphological classes of mature ependymal cells were observed in the cortical cultures. These classes corresponded to the cuboidal, tanycyte and secretory ependymal cell types described in vivo. Direct counting of stained cells showed that these morphological classes were represented in the cultures in roughly the same proportions seen in vivo (cuboidal 75%, tanycyte 19% and secretory 6%). The temporal aspects of ependyma development permitted the staining of developmental stages corresponding to the various morphological classes or types. The morphological sequence of development of the cuboidal cell and tanycyte from the precursor cell or matrix cell--daughter cell was determined. These two cell types displayed marked differences in their developmental sequence. The developmental sequence of the secretory cell could not be resolved; however, what appeared to be multiple morphological subtypes of this cell class were encountered.(ABSTRACT TRUNCATED AT 250 WORDS)

L-pyroglutamate: an alternate neurotoxin for a rodent model of Huntington's disease.

Intrastriatal injections of L-Pyroglutamate (L-PGA) in mice produced behavioral and neuropathological effects that resemble in part the kainate-injected rat striatal model of Huntington's Disease (HD). The behavioral responses induced after unilateral injections of L-PGA included circling, postural asymmetry of head and trunk and possible dyskinesias. The neuropil in the injected striatum contained dilated profiles, degenerating neurons and oligodendroglia, and numerous phagocytic microglial-like cells. A dose response relation existed. The size of the lesion (expressed as a percent volume of the striatum destroyed) ranged from 1 +/- 0.18% at 0.02 mumoles to 20.2 +/- 3.97% at 200 mumoles L-PGA (pH = 7.3). L-PGA is a weak neurotoxin when compared to kainic acid. Several factors raise interest in the possible role of L-PGA in HD, including the recently reported elevated plasma levels of L-PGA in some HD patients, and these considered in the discussion.

Morphological diversity of ependymal cells in tissue culture.

Ependymal cells were visualized in primary cultures of cerebral cortex from rat using an immunohistochemical staining technique. Five different morphological subtypes of cuboidal ependyma were recognized: 1) round, 2) triangular, 3) columnar, 4) cone- and spindle-shaped, and 5) large pleomorphic cells. These cells varied in size and almost all possessed cilia. Two distinct forms of tanycyte ependyma were detected based on the presence of cilia. These features reflect a significant level of development of the ependymal cells in culture and may correspond to functional diversity within this group.

The TPc, the avian substantia nigra: pharmacology and behavior.

The nucleus tegmenti pedunculo-pontinus, pars compacta (TPc) may be the avian analogue of the mammalian substantia nigra (SN). The analogy is suggested by both comparative neuroanatomical and neurohistochemical observations. To test the proposed analogy certain drugs (agonists or antagonists of putative transmitters that modulate the dopaminergic and GABAergic systems in rat) were injected into the TPc of the pigeon and the behavior effects observed. Muscimol (a GABA agonist) injected into the caudal TPc induced contralateral rotation and postural asymmetries. Pretreatment with subcutaneous injections of apomorphine hydrochloride enhanced and haloperidol suppressed the rotatory response, while the postural asymmetries were not altered by either drug. Muscimol injected into the rostral TPc induced contralateral rotation, marked ataxia, and postural asymmetries, particularly the head and neck, legs and wings. Whereas apomorphine (subcutaneous injection) was without effect on the rotatory response to muscimol, haloperidol suppressed the rotatory response. Neither drug effected the postural asymmetry. Following drug injections into either the pigeon TPc or the rat SN the behaviors induced in both bird and rat suggest that the TPc and SN are analogous.

Forebrain projections of the pigeon olfactory bulb.

The olfactory system of the pigeon (Columba livia) was examined. Our electrophysiological and experimental neuroanatomical (Fink-Heimer technique) data showed that axons from the olfactory bulb terminated in both sides of the forebrain. The cortex prepiriformis (olfactory cortex), the hyperstriatum ventrale and the lobus parolfactorius comprised the uncrossed terminal field. The crossed field included the paleostriatum primitivum and the caudal portion of the lobus parolfactorius, areas which were reached through the anterior commissure. In this report the relationships between areas that receive olfactory information and the possible roles that olfaction plays in the birds' behavior are discussed.

Chronic intrastriatal injection of the excitatory amino acid receptor antagonist L-kynurenic acid in rat produces selective neuron sparing lesions.

Heritable neurodegenerative diseases may be associated with one or more endogenous neurotoxins whose actions on neurons lead to the degenerative changes. One metabolite of tryptophan, the amino acid L-kynurenic acid (L-KYN), was chronically injected into the striatum of the male rat to test its potential as an endogenous neurotoxin. L-KYN, at concentrations of approximately five times its normal brain levels, produced a large lesion with relative selective neuron sparing. The L-KYN-induced lesion presented three concentric regions: a central necrotic zone, a thin pyknotic zone, and an outermost spongiose zone. The number of GABA-ergic neurons were markedly reduced (approximately 76%), while cholinesterase-positive neurons were also lost. The NADPH diaphorase-positive neurons were the most resistant to L-KYN neurotoxicity and were spread throughout the spongiose zone. The brain levels of L-KYN are abnormal in patients with the neurodegenerative disorder Huntington's disease and as a neurotoxin L-KYN may play a role in the etiology of this disease. Of further significance, the fact that L-KYN is neurotoxic contraindicates the use of this excitatory amino acid receptor antagonist as a therapeutic agent in the treatment of neurodegenerative disorders.

Thalamic arterial pattern: an endocast and scanning electron microscopic study in normotensive male rats.

Rat cerebral vasculature serves as a model for study of the pathophysiology of stroke in humans. Human thalamic arteries show a high incidence of stroke. The objective is to describe the thalamic arterial vascular pattern in normotensive male rats as the initial step for quantitative histochemical studies of enzyme activities in the walls of these vessels. Intracardiac injections of methyl methacrylate monomer provide detailed vascular endocasts. The thalamic vascular bed defined by in situ dissection, serial reconstruction, and light and scanning electron microscopy of endocasts contained four groups of vessel: ventral medial thalamic arteries, thalamic branches from the posterior cerebral artery, and ventral lateral and ventral anterior thalamic arteries. Thalamic vessels are muscular arterioles that, after three to four bipinnate branches, feed into a continuous capillary bed (no loops). The parent vessels and their subsequent branches have been evaluated in terms of their mean internal diameters, mean interbranch intervals, and branch angles. The arterial patterns to rat and human thalami are very similar, with the exception of the anterior choroidal artery which is missing in the rat. The branches supplying the thalamus in both the rat and human are closely associated with the circle of Willis; however, the constituent parts of the circle in rat vary from the pattern in human brain. The rat thalamic arteries show morphological features similar to those seen in the stroke-prone ganglionic arteries in the human basal ganglia.

A histochemical study of cerebral cortical vessels and ganglionic vessels of the caudatoputamen in aging normotensive rats.

The goal was to describe the metabolic profile of ganglionic and cortical arteries and arterioles in aging normotensive male rats. Five enzymes indicative of key metabolic pathways in the vessel walls were semiquantitatively evaluated using bright-field histochemical microscopy. Lactate dehydrogenase showed significant reactivity which increased with vessel diameter in cortical and ganglionic vessels in all age groups tested. Succinate dehydrogenase and cytochrome oxidase showed little reactivity in both cortical and ganglionic vessels, suggesting a reduced role for aerobic metabolic pathways. Myosin ATPase reactivity was high in cortical and ganglionic vessels. Only this enzyme showed an increased reactivity that was correlated with the age and diameter of the vessel. Glucose-6-phosphate dehydrogenase reactivity was more pronounced in cortical than ganglionic vessels, suggesting that the hexose-monophosphate-shunt may be more active in the cortical vessels. There were no regional differences in enzyme reactivity throughout the caudatoputamen. In conclusion, both the cortical and ganglionic vessels are metabolically active, with significant anaerobic glycolysis, and reduced, but observable capacity for aerobic metabolism. The decreased myosin ATPase reactivity and the low level of glucose-6-phosphate dehydrogenase reactivity in the ganglionic arterioles of senescent rats may contribute to the susceptibility of these vessels to cerebrovascular accidents.

A technique for improved fixation of the pigeon central nervous system for electron microscopy.

The central nervous system (CNS) of the pigeon has been difficult to fix with consistency, and consequently this problem has impeded ultrastructural studies of various parts of the pigeon brain. Here we describe a method for effective fixation of the pigeon CNS and discuss the three principal problems associated with good fixation of this animal's brain. The animal was deeply anesthetized and the thoracic cavity was opened without collapsing the pectoral girdle upon the brachiocephalic trunks and the common carotids. The perfusion pressure was raised to 140-150 mm Hg to overcome the high resistance of the small diameter, long common carotids. Heparin was added to the wash buffer to retard coagulation of blood in the vascular bed of the brain. The method is not foolproof, but with care excellent fixation can be achieved.