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PubMed2025

Dynamic Molecular Changes in Brain, Lung, and Heart of Hamsters Infected With SARS-CoV-2: Insights From a Severe and Recovery Phase Model.

The Global pandemic of coronavirus disease 2019 was initiated by the emergence of severe acute respiratory syndrome coronavirus 2. In addition to conventional pulmonary lesions, a range of neurological injury symptoms have been identified in clinical practice, but the aetiology of neurological disorders linked to SARS-CoV-2 infection remains poorly understood. Syrian hamsters, which are highly susceptible to SARS-CoV-2 infection, exhibit a disease phenotype similar to that observed in human COVID-19 patients. In this study, a hamster model of COVID-19 infection was used to analyze molecular changes in different tissues at various time points post infection with distinct strains using proteomic and phosphoproteomic approaches. Multi-omics analysis showed that SARS-COV-2 infection triggers sustained downregulation of the abundance and phosphorylation levels of neuronal and synapse-associated proteins in the brain, suggesting that neuronal damage persists even during the recovery period. Additionally, infections with SARS-CoV-2 may contribute to the onset of long-term symptoms of COVID-19 by impacting energy metabolism, neurotransmitter release, and synaptic transmission pathways. This study provides a comprehensive molecular profile of hamsters infected with different SARS-CoV-2 strains in different tissues, offering foundational insights into the pathogenic mechanisms of COVID-19.

Animals↗
PubMed2003

Repeated dose oral toxicological evaluation of concentrated barley beta-glucan in CD-1 mice including a recovery phase.

The cholesterol-lowering effect observed following consumption of oats and barley is attributable to the beta-glucan component of the soluble fiber fraction of these cereal grains. beta-Glucan has also been reported to modulate immune activity, however, few studies have evaluated the hematological effects of beta-glucan following oral exposure. In the current study, a concentrated beta-glucan (64%) preparation from barley (Barley Betafiber) was blended into mouse feed at concentrations of 1, 5, or 10% (corresponding to approximately 0.7, 3.5, and 7% beta-glucan) and evaluated in CD-1 mice. Plasma was collected for clinical chemistry and hematological measurements at the initiation of the study and again following 14 and 28 days of exposure. Plasma was also collected from animals that consumed the same diets for 28-days but were switched to control diet (containing no supplemental beta-glucan) for an additional 14-day period to evaluate reversibility or delayed occurrence of treatment-related changes. Half of the animals were sacrificed for histopathologic analysis following the 28-day exposure period and the other half were evaluated following the recovery period. Histopathologic analysis focused on primary lymphoid organs and lymph nodes proximal and distal to the route of exposure. An additional group of untreated animals (nai;ve) was bled and sacrificed at day 0, 14, 27 and 41 for comparison of the hematology parameters with those of the control group because it was not known if multiple blood draws would affect hematology parameters. Compared to animals consuming the control diet, no treatment-related adverse effects were observed in hematological or clinical chemistry measurements or in organ weights and immunopathology in either sex following consumption of concentrated barley beta-glucan for 28-days or following the recovery period. Likewise, no differences were observed between the nai;ve and control groups. Results from this study showed that consumption of concentrated barley beta-glucan did not cause treatment-related inflammatory or other adverse effects in CD-1 mice.

Animal Feed↗
PubMed2000

Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen.

BACKGROUND: The pathogenesis of inflammatory bowel disease is still unknown. However, it is possible that faecal bile acids influence the clinical course. AIMS: To evaluate the eliminating effects of faecal bile acids by the oral adsorbent on dextran sulphate sodium-induced rat colitis. METHODS: Rats were given 3% dextran sulphate sodium aqueous solution for 7 days, with or without concomitant administration of oral adsorbent, or the rats were given dextran sulphate sodium for 7 days, followed with or without oral adsorbent for 5 days. Macroscopic and microscopic examinations of the colons and measurement of faecal bile acids were performed. The cytotoxicity of bile salts on Caco-2 cells was also evaluated. RESULTS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis. Oral adsorbent was fairly effective in reducing faecal hyodeoxycholic acid concentration. A positive correlation was found between the size of the ulcer area and the faecal hyodeoxycholic acid concentration. In a cell culture study, cytotoxicity of bile acid was parallel with increasing hydrophobicity of the bile acid. However, hyodeoxycholate exhibited severe cytotoxicity, despite its hydrophilic properties. CONCLUSIONS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis and tended to promote the recovery process. It is possible that bile acids in the gut lumen influence the progression of dextran sulphate sodium-induced colitis and its repair process.

Acute Disease↗
PubMed1991

Intermediary metabolism in renal proximal tubules in the recovery phase of experimental renal ischemia in dogs.

Intermediary metabolism has been studied in a viable suspension of renal proximal tubules isolated from dogs before and after 48 h of a 60 min period of renal ischemia by clamping the renal artery. The study consisted in measurements of tubular uptake/production of glucose, lactate, glutamine, glutamate, alpha-ketoglutarate, alanine, ammonium, and oxygen, using as substrates either glutamine 1 or 5 mM (+ glutamate 0.1 or 0.5 mM) or lactate 1 or 5 mM (+ pyruvate 0.1 or 0.5 mM). The combination of glutamine + lactate was also studied. Data revealed that the gluconeogenic ability of the postischemic tubules was maintained, with the exception of glutamine 5 mM as substrate (8.5 +/- 2.1 vs 15.4 +/- 2.1 mumol/min/g in control tubules). The production of NH4 was also decreased only with this substrate (from 214 +/- 15 to 165 +/- 9 mumol/min/g). Lactate extraction was decreased in the postischemic tubules, but the difference was only significant when lactate + glutamine 1 mM was used as substrate (72 +/- 12 vs 44 +/- 6 mumol/g/min). Postischemic tubules showed a greater oxygen consumption when either glutamine or lactate 1 mM were used, but lower ouabain-inhibitable O2 consumption when these substrates were used at 5 mM. These data revealed a modification of the metabolic profile of proximal tubules during the recovery of transient renal ischemia.

Alanine↗
PubMed1975

The effect of convulsions induced by flurothyl on ribonucleic acid synthesis in rat cerebral cortex during the recovery phase.

The effect of convulsions, induced by flurothyl, on RNA synthesis in purified unfractionated nuclei and the cytoplasm of rat cerebral cortex was studied by using a double-label technique involving injection of [3H]- and [14C]-orotate intracisternally. 2. Intact RNA was extracted in 80% yield by an enzymic method by using a proteinase in the presence of sodium dodecyl sulphate followed by deoxyribonuclease. Electrophoresis on 1.5% polyacrylamide-0.5% agarose gels revealed the presence of giant nuclear RNA of size up to approx. 300X 10(6) daltons and mRNA of maximal mol.wt. 9 X 10(6)-16 X 10(6). 3. Nuclear RNA synthesis was decreased to 27% in the first 15 min after convulsions but rapidly increased, so that at 1 1/2 h it was 124% of the control, and at 6 h 147%. 4. Labelling of cytoplasmic RNA was decreased to 15% at 15 min after convulsions but had not recovered to control values by 6 h. 5. Analysis of radioactive gel patterns and the 3H/14C ratio at six time-points (15 min-6h) showed that the major effect was inhibition of the processing of heterogeneous nuclear RNA resulting in a sharp decline in the export of newly synthesized RNA from the nucleus. 6. Cytoplasmic RNA patterns indicated that specific messengers were synthesized at different times during the recovery of the cell after convulsions.

Animals↗
PubMed1996

Collagen-induced arthritis in CD4- or CD8-deficient mice: CD8+ T cells play a role in initiation and regulate recovery phase of collagen-induced arthritis.

Collagen-induced arthritis (CIA) is an experimental autoimmune disease induced by immunization with collagen type II (CII). We studied CIA in CD4- or CD8-deficient DBA/1 mice to further define the roles of CD4+ and CD8+ T cells in the disease. CD4-deficient mice developed severe arthritis, and no differences in incidence, clinical course, and severity were observed between CD4 -/- and CD4 +/- mice. Proliferative responses of lymph node T cells to CII was, however, reduced in CD4 -/- mice, and inflamed joints revealed relative accumulation of CD4-CD8-TCR(alpha)(beta)+ cells. A CII-specific T cell line generated from CD4-deficient mice responded to CII in a MHC-restricted fashion and had a CD4-CD8-TCR(alpha)(beta)+ phenotype. Disease incidence in CD8 -/- mice was significantly decreased compared with CD8 +/- mice, even though the severity of arthritis in arthritic mice was not different. These results suggests a role for CD8+ T cells in initiating CIA. Interestingly, CD8-deficient mice were more susceptible to a second induction of arthritis after remission of initial disease, pointing towards an immunoregulatory role for CD8+ T cells. CD8-deficient mice did not, however, show any defect in oral tolerance induction using CII. Taken together, our findings demonstrate that CD4-CD8-TCR(alpha)(beta) cells can trigger systemic arthritis in CD4-deficient mice and that CD8+ T cells can play dual and opposing roles, important both in initiation of CIA and in providing resistance to reinduction of CIA after recovery from initial disease.

Animals↗
PubMed1999

Fast and slow recovery phases of goldfish behavior after transection of the optic nerve revealed by a computer image processing system.

As the goldfish is a common experimental animal for vision research, including psychophysical behavior, it is very important to quantitatively score fish behavior. We have previously developed a computer image processing system which can acquire the positional coordinates of goldfish moving freely in an aquarium and determine turning directions (go straight, right or left turn). In the present study, an algorithm to determine tilting angles of moving goldfish was constructed. We also made histograms for quantifying the interaction between pairs of goldfish (two-point distance). By using these histograms, we estimated the time-course of behavioral regeneration after optic nerve transection in goldfish. Control goldfish showed an equal percentage of right or left turns and maintained an upright position in a dorsoventral axis. When the optic nerve of a goldfish was unilaterally sectioned, the goldfish showed predominant turning and slight tilting toward the intact eye. The abnormal turning and tilting behaviors lasted for 10-14 days and then gradually decreased, returning to control behaviors by one month after the unilateral transection. When the optic nerve of a single goldfish was bilaterally sectioned, it did not show any preferential turning and tilting behavior, which is similar to what was observed in control goldfish. However, the trace maps showed that, after bilateral sectioning, fish preferred to cross the center of the tank, which was unlike control fish. In control pairs, one goldfish chased the other with a fixed small range of two-point distances. However, in pairs of goldfish with bilateral transection of the optic nerve, the blind goldfish behaved independently of each other, with a long two-point distance. The long two-point distance of the blind goldfish lasted for at least two months and then slowly returned to control two-point distance by four months after bilateral transection. Such fast and slow recovery in goldfish behaviors evoked after unilateral and bilateral transection of the optic nerve is discussed with respect to reconnection of regenerating optic nerves in the fish central nervous system. This computer image processing system is a useful tool with which we can quickly and easily quantify fish behavior.

Algorithms↗
PubMed1993

Decreased levels of the high molecular weight subunit of neurofilaments and accelerated neurofilament transport during the recovery phase of 2,5-hexanedione exposure.

The neurotoxicant 2,5-hexanedione (HD) causes the accumulation of neurofilaments in the distal axon and an acceleration of neurofilament transport proximal to the site of their accumulation. It has been proposed that the acceleration of transport is due to the direct reaction of HD with neurofilament proteins and, conversely, that this acceleration is a secondary response to the axon to injury. The objective of this study was to determine whether the response of axons to HD intoxication includes acceleration of neurofilament transport. Pulse labelling was used to analyze neurofilament transport in age-matched rats exposed to HD or PBS. The animals receiving HD were exposed either throughout the period of radiolabel transport, or prior to the pulse labeling of neurofilament proteins. If acceleration of the rate of neurofilament transport was due to the direct reaction of HD with proteins, then neurofilaments synthesized after the exposure period should travel at control rates, since these proteins would not have been exposed to the toxicant. After 28 days of transport, optic nerve proteins were examined using SDS-PAGE, fluorography, and computerized densitometry. In both HD-treated groups, neurofilament transport was accelerated relative to age-matched control animals. In addition, the amount of NFH was decreased relative to other neurofilament subunits. The combination of accelerated transport and a diminished proportion of NFH is similar to the observations of neurofilament axonal transport during growth and development. These observations suggest that this persistent, secondary effect is a reparative response to injury that recapitulates axonal growth and development.

Animals↗
PubMed1999

Enhanced expression and localization of heme oxygenase-1 during recovery phase of porcine stunned myocardium.

Myocardial adaptation to ischemia involves up-regulated expression of a number of genes implicated in conferring cytoprotection. We have previously shown that myocardial ischemia followed by reperfusion leads to a co-ordinated expression of mRNAs encoding heme oxygenase-1 (HO-1) and ubiquitin in pigs. HO-1 participates in biological reaction leading to the formation of the antioxidant, bilirubin and the putative cellular messenger, carbon monoxide. In the present study, we examined the expression and cellular localization of HO-1 in the heart during myocardial stunning in anesthetized pigs. After thoracotomy, the LAD was occluded for 10 min and reperfused for 30 min (group I, n = 4), again occluded for 10 min and reperfused for 30 min (group II, n = 6), 90 min (group III, n = 4), 210 min (group IV, n = 5) and for 390 min (group V, n = 4). Myocardial tissue specimens were collected in 10% formalin as well as in liquid nitrogen and processed for immunohistochemistry and mRNA expression analysis, respectively. In the distribution territory of the LAD (experimental, E), systolic wall thickening was significantly decreased (39 +/- 6%) as compared to that of the area perfused by left circumflex coronary artery (LCx, control) in group I and remained depressed in all subsequent groups. Northern blot analysis revealed that the expression of a single mRNA species of 1.8 kb encoding HO-1 was significantly induced in E as compared to control in groups II and III with maximum mRNA levels in group II (1.9 +/- 0.4 fold vs. control). Immunoreactive HO-1 was localized in the cytoplasm of cardiomyocytes as well as in the perivascular regions in all groups. Semiquantitative analysis of HO-1 staining showed significantly enhanced levels of HO-1 in perivascular region in E as compared to respective controls derived from groups III and IV. These results suggest that myocardial adaptive response to ischemia involves up-regulation of HO-1 in cells of perivascular region indicating that this enzyme may participate in regulating vascular tone via CO and thereby, contributing in pathophysiologically important defense mechanism(s) in the heart.

Animals↗
PubMed1980

Alcoholic liver disease. Absence of alpha-fetoprotein elevations in the recovery phase.

Serum alpha-fetoprotein (AFP) may be detected in patients with nonneoplastic liver diseases such as massive hepatic necrosis, viral hepatitis, and experimental liver injury, AFP levels have not been serially assessed in patients with alcoholic liver disease, with or without cirrhosis, during the period following cessation of alcohol. Thirty-two such patients were studied with weekly AFP determinations, an average of five such measurements being obtained per patient. The severity of alcoholic liver disease in this group varied from mild alcoholic hepatitis to advanced cirrhosis, and overall mortality was 31%. Thirty-one of the 32 patients had consistently negative AFP determinations. One patient with persistently elevated AFP levels proved to have hepatoma at autopsy. This study failed to detect AFP evelations in a group of patients with alcoholic liver disease and suggests that positive AFP determinations in such patients shoudl raise the question of underlying hepatocellular carcinoma.

Female↗
PubMed1991

Severe non-hypoxic bradycardia during disconnection from the ventilator during the recovery phase of ARDS.

Four patients with adult respiratory distress syndrome developed sinus bradycardia during weaning procedures with no evidence of hypoxemia. Bradycardia occurred immediately after the patients' endotracheal tubes were disconnected from the ventilator and most of the time resolved after reconnection. However, 3 patients eventually deteriorated, requiring advanced life support and for one of them, cardiac pacing. The precise mechanism of these bradycardic episodes remains unclear but was unrelated to hypoxemia or acid-base disorder.

Adolescent↗
PubMed1990

Role of left ventricular dysfunction in selective neurohumoral activation in the recovery phase of anterior wall acute myocardial infarction.

Neurohumoral activation is readily apparent in patients with symptomatic congestive heart failure (CHF) and in the acute phase after acute myocardial infarction. In this study, the neurohumoral profiles of 36 asymptomatic patients in the early convalescent phase after acute myocardial infarction were examined. All patients in the study had a radionuclide ejection fraction less than or equal to 45% and underwent cardiac catheterization 11 to 30 days after infarction. Venous blood samples were obtained in the supine state for the measurement of norepinephrine, angiotensin II, plasma renin activity and aldosterone in all patients. Despite the reduced ejection fraction and extensive wall motion abnormalities, plasma norepinephrine was not elevated and did not correlate with any measured hemodynamic, angiographic or clinical variables. The renin-angiotensin II aldosterone system was activated, as expected, in the 9 study patients receiving loop diuretics. However, even in the 27 patients not taking diuretics, plasma angiotensin II and renin activity levels were increased in relation to Killip classification, the presence of a left ventricular (LV) aneurysm and LV ejection fraction. Activation of the renin-angiotensin-aldosterone system can be identified in hemodynamically compensated postinfarction patients not taking diuretics and appears to be related to the extent of LV dysfunction.

Aged↗
PubMed1994

Morphometric analysis of the deposition and mineralization of enamel and dentine from rat incisor during the recovery phase following a low-calcium regimen.

The administration of a low-calcium diet to pups nursed by a mother on the same diet has been shown to induce a slowing of growth. A reduction of the apposition rate of dentine, which was normally mineralized, and a dramatic reduction of the extent of mineralization of enamel, whose organic matrix was otherwise produced in an almost normal amount, was observed in the incisors of these animals. Modifications of the mineral apposition rate of dentine, measured after administration of tetracycline (10 mg/kg), and the thickness and the microhardness of the two tissues, the latter being an expression of the degree of mineralization, were now investigated when hypocalcic pups were restored to a normal-calcium diet for 10 or 60 days. Enamel microhardness was increased by more than 60% after only 10 days of restored diet and had become the same as in the control tissue after 60 days, without any significant increase in thickness. Dentine thickness and mineral apposition rate increased significantly, to become similar to those of the controls after 60 days of restored diet. In dentine there was no significant variation of microhardness between experimental pups and controls, either during the low-calcium diet or the restorative period. These results indicate that the deposition of the organic matrix of enamel is a process independent from that of its mineralization, and that the mineralization of the organic matrix happens by its replacement even a long time after its deposition. In contrast, the deposition and mineralization of dentine are strictly interdependent processes, at least in these experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Attention/information processing, neuropsychological functioning, and thought disorder during the acute and partial recovery phases of schizophrenia: a longitudinal study.

Schizophrenic subjects were administered the span of apprehension task, which is a measure of visual information processing; two neuropsychological tests; and measures of specific aspects of thought disorder and general clinical state. The measures were administered both when patients were acutely disturbed and when they were partially recovered. Normal control subjects were tested over a comparable 12-week interval. Improvements in both overall clinical condition and specific aspects of thought disorder occurred in the schizophrenic patients during this time. The patients, however, continued to show impaired information processing, indicating that the span of apprehension task is sensitive to schizophrenic dysfunction across wide variations in clinical state and, therefore, may be a marker of vulnerability to schizophrenia. The span of apprehension task was found to be significantly correlated with a measure of thought disorder that assesses resistance to associative distractors and two neuropsychological tests--the Trail-Making Test from the Halstead-Reitan battery and the Digit Symbol Substitution Test--during the testing session conducted while the subjects were partially recovered.

Acute Disease↗
PubMed1988

Audiological management in the recovery phase of bacterial meningitis.

During a specified 12-month period, a prospective study of all children admitted to a 139-bed city children's hospital with confirmed bacterial meningitis enabled assessment audiologically at 48 h, 6 weeks and 12 weeks post-admission using a test battery approach including auditory brainstem evoked responses and tympanometry. Results suggested conductive dysfunction to be a major cause of fluctuating hearing loss within the group. The incidence of sensori-neural loss was 16.6% of ears tested at final outcome. Results are discussed with reference to their implications for audiological management.

Acoustic Impedance Tests↗
PubMed1975

Subacute thyroiditis in a lateral thyroid gland: evaluation of the pituitary-thyroid axis during the acute destructive and the recovery phases.

Subacute thyroiditis in a lateral, ectopic thyroid has been previously unreported. A 4 10/12-YEAR-OLD GIRL HAD AN ENLARGING MASS IN THE LEFT UPPER ANTERIOR NECK. Initially, the serum concentration of T4 was normal, T3 was elevated, and TSH was undetectable without response to TRH. RAI uptake was 1%. The data were consistent with subacute thyroiditis. Twelve weeks later the serum concentration of T4 was low and TSH was elevated; thyroid replacement therapy was given for 20 weeks. When this was discontinued, there was an initial increase and then a decrease in the TSH values accompanied by an increase in serum concentrations of T3 and T4 to normal during eight weeks. One must consider a lateral ectopic thyroid gland in the differential diagnosis of masses in the neck. Physicians must be aware that temporary hypothyroidism occurs during the course of subacute thyroiditis.

Acute Disease↗