scholarly journals Evaluation of Antigenicity of Components of Tracheal Allotransplant and Effect of Immunosuppressant Regime in a Rodent Model

2020 ◽  
Vol 53 (03) ◽  
pp. 357-362
Author(s):  
Dimpy Sharma ◽  
Subramania Iyer ◽  
Sobha Subramaniam ◽  
Janarthanan Ramu ◽  
Mohit Sharma ◽  
...  

Abstract Background Tracheal transplantation seems to be the logical step in the process of reconstruction of the trachea following a long-segment resection, which is usually done to treat malignant disease or benign stenosis of the airway caused by a traumatic, congenital, inflammatory, or iatrogenic lesion. Immunosuppression following transplant is essential but not ideal after oncoresection. Methods The tracheal allografts, harvested from Sprague Dawley rats, were implanted in the Wistar strain rat. The harvested tracheal grafts were divided into groups and subgroups, based on the layers of trachea, method of decellularization, and immunosuppression. The antigenicity of different layers of trachea and the effect of various decellularization methods were studied within three time frames, that is, day 3, 9, and 15. Result On structural analysis, the day 3 and day 15 samples showed no meaningful comparison could be made, due to extensive neutrophil infiltration in all three layers. The day 9 tracheal grafts showed loss of epithelium, with no signs of regeneration in most of the allografts. The subepithelial lymphoid infiltration was found to be severe in nonimmunosuppressed allografts. The group in which both inner and outer layers were removed showed moderate-to-severe infiltrate of lymphoid cells in all the allografts, but there was no cartilage loss, irrespective of the method of decellularization. The irradiated specimens retained the cartilage but showed extensive ischemic damage. Conclusion Rat trachea is a good model for tracheal transplant research but not adequately sturdy to sustain mechanical debridement. Irradiation and chemical decellularization eliminates the immune response but causes intense ischemic damage. Out of the three time frames, day 9 seemed to be the best to study the immune response. To substantiate the results obtained in this study, the immunohistochemical study of the allografts is needed to be performed among a larger group of animals.

2001 ◽  
Vol 91 (4) ◽  
pp. 1828-1835 ◽  
Author(s):  
Nicole Stupka ◽  
Peter M. Tiidus

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.


Blood ◽  
1969 ◽  
Vol 33 (5) ◽  
pp. 717-726
Author(s):  
KIYOYASU NAGAI ◽  
EIZO KAKISHITA

Abstract The change in radioactivity of bilirubin with time was measured after injection of glycine 2-14C into rats with a bile fistula. The total radioactivity and specific activity of bilirubin were abnormally high in rats of which erythropoiesis was increased following hemorrhage. When the newly formed erythrocytes labeled with glycine 2-14C in the peak of reticulocytosis were transfused into rats with a bile fistula, the excretion of labeled bilirubin increased rapidly. The amount of newly formed erythrocytes destroyed within 7 days after transfusion into normal animals was calculated as 4.4 per cent of the total erythrocytes formed during maximum reticulocytosis and 1.1 per cent of those formed in the normal state in Sprague Dawley rats, while in the Wistar strain, the values were 13.4 per cent and 2.2 per cent, respectively. These results provide direct evidence for increased production of short-lived erythrocytes during enhanced erythropoiesis, and the hemolysis of newly formed erythrocytes soon after they reach the general circulation may contribute to the production of shunt bilirubin.


1972 ◽  
Vol 135 (4) ◽  
pp. 808-826 ◽  
Author(s):  
Alan E. Beer ◽  
R. E. Billingham ◽  
S. L. Yang

A previous report that the offspring of outbred Sprague-Dawley rats, born of mothers presensitized or tolerant with respect to tissue antigens of the Lewis strain, and reinoculated with Lewis cells during their pregnancy, reject test grafts of Lewis skin in an accelerated manner has been confirmed. This "maternally induced" alteration in reactivity of the progeny has been found to be long lasting, immunologically specific, and probably not due to transfer of humoral antibody. It has been established that the reexposure of the mothers to donor cellular antigen during pregnancy augmented the influence of the prior states of tolerance or sensitivity. To obviate the complications inherent in working with the outbred Sprague-Dawley rats, the key experiments summarized above were repeated with isogenic Fischer rats as parents and Lewis rats as the tissue donors as before. With this combination it was found that a state of prior sensitization or tolerance in the mothers resulted in the apparent induction of tolerance in some of their progeny. Reinoculation of either the tolerant or sensitized mothers during pregnancy slightly increased the incidence and degree of impairment of their offsprings' capacity to reject Lewis skin grafts. A single intraperitoneal injection of 100 x 106 million Lewis lymphoid cells into normal Fischer rats in the 14th–16th day of pregnancy also weakened the reactivity of their progeny to Lewis test grafts. Further to test the premise that this weakened reactivity might be due to maternal induction of tolerance, by antenatal transmission of alien cells, the lymphohematopoietic tissue system of adult Fischer females was replaced by that from Lewis donors with the aid of cyclophosphamide. It was anticipated that when these animals were mated with Fischer males, sufficient Lewis leukocytes might cross the placentas to induce high degrees of tolerance. Although normal sized healthy litters were born, about 50% of the infants succumbed to graft-versus-host (GVH) or runt disease within 40 days, many of them giving evidence of being tolerant of Lewis grafts. The mothers, too, developed chronic GVH disease. The offspring of Fischer females made chimeric with cells from (Fischer x Lewis)F1 hybrid donors, as well as their mothers, remained healthy. Intraperitoneal injection of normal Fischer females, in the 15th–17th day of pregnancy, with 100 million lymphoid cells from specifically sensitized Lewis rats, also caused fatal runt disease to develop in about 50% of their offspring, but left the mothers unscathed. Taken together, these various findings indicate that in some genetic contexts at least the extent of the natural surreptitious transplacental cellular traffic can be considerably augmented experimentally, though how this comes about and why lymphocytic cells that are foreign to the mother can apparently gain access to fetuses more readily than her own cells remain to be determined.


2020 ◽  
Author(s):  
Stephen Antwi ◽  
Daniel Oduro-Mensah ◽  
David Darko Obiri ◽  
Clara Lewis ◽  
Ebenezer Oduro-Mensah ◽  
...  

Abstract Ethnopharmacological relevance In Ghanaian folk medicine, Holarrhena floribunda has anecdotal use for the treatment of inflammatory conditions. A hydro ethanol extract of the stem bark has previously been shown to be effective in the management of acute inflammation and anaphylaxis in rodents.Aim of the study This study was aimed at evaluating the usefulness of H. floribunda stem bark hydro ethanol extract (HFE) for the management of chronic inflammation in a murine model.Materials and Methods Anti-arthritic effect of the extract was evaluated using Complete Freund’s Adjuvant-induced arthritis in male Sprague-Dawley rats. Using both prophylactic and therapeutic treatment models, parameters assessed included oedema, serology of inflammatory response, radiology, bone tissue histology and haematology. Data were analysed by ANOVA followed by Tukey’s multiple comparisons post hoc test.Results HFE at 50–500 mg/kg dose-dependently [P ≥ 0.0354 (prophylactic) and P ≥ 0.0001 (therapeutic)] inhibited swelling of the injected paw upon prophylactic [≤ 81.26 % (P < 0.0001)] or therapeutic [≤ 67.92 % (P < 0.01)] administration — and prevented spread of arthritis to the contralateral paw. Inflammation alleviation activity of HFE was further demonstrated by decrease in arthritis score, radiologic score and erythrocyte sedimentation rate. HFE at all doses significantly reduced serum IL-1α (P < 0.0197), and 500 mg/kg HFE reduced serum IL-6 (P = 0.0032). In contrast, serum concentrations of IL-10, protein kinase A and cyclic adenosine monophosphate were enhanced (P ≤ 0.0436). HFE consistently showed better prophylactic activity than when administered therapeutically.Conclusions The data demonstrate that HFE suppresses CFA-induced arthritis and modulates regulators of inflammation; including IL-1α, -6 and -10 which also play mediatory roles in several immune response pathways. These make HFE a strong candidate for development as an agent for management and modulation of inflammation and the inflammatory response, including immune response-related adverse events such as seen in severe COVID-19.


Parasitology ◽  
1965 ◽  
Vol 55 (4) ◽  
pp. 711-717 ◽  
Author(s):  
S. R. Smithers ◽  
R. J. Terry

The host–parasite relationships of Schistosoma mansoni in the albino rat have been studied recently by Ritchie, Garson & Knight (1963) and by Sadun & Bruce (1964). The general findings of these and other workers are that, in rats, the worms are always stunted, although they may pair and non-viable eggs may be found in the liver. The worms remain in the liver and seldom, if ever, migrate to the mesenteries. Ritchie et al. (1963) found that the majority of the worms were eliminated between the 4th and 8th week after infection; this is much sooner than in other experimental hosts. Sadun & Bruce (1964) suggest that rats are particularly suitable and convenient for studies on acquired resistance to S. mansoni; this suggestion is based mainly on the grounds that acquired resistance is more easily demonstrated in animals which show a relatively great degree of innate resistance.The present work has been undertaken in order to establish whether the immune response in the albino rat is at all similar to that in the rhesus monkey (Smithers & Terry, 1965b). Two features of the host–parasite system have been studied in detail; the elimination of the worms which follows an initial infection and a comparison of the development of acquired resistance following exposure to X-irradiated cercariae with that following exposure to normal cercariae.A Puerto-Rican strain of S. mansoni, and Sprague–Dawley rats weighing 100–200 g, were used in all experiments. The methods of exposing the rats percutaneously to infection and the recovery of the worms by perfusion have been fully described (Smithers & Terry, 1965 a).


2009 ◽  
Vol 3 (05) ◽  
Author(s):  
Byeong Kirl Baek ◽  
Mst. Minara Khatun ◽  
Md. Ariful Islam ◽  
Sung Il Lee

1983 ◽  
Vol 2 (2) ◽  
pp. 165-174 ◽  
Author(s):  
N. W. Revis ◽  
T. C. Major ◽  
C. Y. Horton

Previous investigators, using an in vitro system, have shown that cadmium inhibits neuronal uptake of norepinephrine (NE). The current studies were performed to determine if the adrenergic system is altered in the cadmium-induced hypertensive rat. The results show that the Fischer and Sprague-Dawley rats develop hypertension, whereas the Wistar normotensive and Wistar hypertensive rats develop hypotension when exposed to 5 ppm of cadmium via drinking water. Results from these studies also show that in the cadmium-induced hypertensive rat, plasma NE is significantly elevated and that plasma clearance of [3H]NE is significantly reduced. However, the changes in NE metabolism observed in the hypertensive rats were also observed in hypotensive rats. Furthermore in the Wistar strain, renal artery cadmium levels were significantly higher than observed in the other two strains. We thus, suggest that the direction of change in blood following cadmium treatment is associated with both the plasma level of norepinephrine and the arterial level of cadmium.


2001 ◽  
Vol 69 (7) ◽  
pp. 4210-4216 ◽  
Author(s):  
Martin A. Taubman ◽  
Cynthia J. Holmberg ◽  
Daniel J. Smith

ABSTRACT Coimmunization with peptide constructs from catalytic (CAT) and glucan-binding (GLU) domains of glucosyltransferase (GTF) of mutans streptococci has resulted in enhanced levels of antibody to the CAT construct and to GTF. We designed and synthesized a diepitopic construct (CAT-GLU) containing two copies of both CAT (B epitope only) and GLU (B and T epitope) peptides. The immunogenicity of this diepitopic construct was compared with that of individual CAT and GLU constructs by immunizing groups of Sprague-Dawley rats subcutaneously in the salivary gland vicinity with the CAT-GLU, CAT, or GLU construct or by treating rats by sham immunization. Levels of serum immunoglobulin G (IgG) antibody to GTF or CAT in the CAT-GLU group were significantly greater than in GLU- or CAT-immunized groups. Immunization with CAT-GLU was compared to coimmunization with a mixture of CAT and GLU in a second rodent experiment under a similar protocol. CAT-GLU immunization resulted in serum IgG and salivary IgA responses to GTF and CAT which were greater than after coimmunization. Immunization with the diepitopic construct and communization with CAT and GLU constructs showed proliferation of T lymphocytes to GTF. Immunization with either the CAT or GLU construct has been shown to elicit significant protection in a rodent dental caries model. Similarly in this study, the enhanced response to GTF after immunization with the CAT-GLU construct resulted in protective effects on dental caries. Therefore, the CAT-GLU diepitopic construct can be a potentially important antigen for a caries vaccine, giving rise to greater immune response than after immunization with CAT, GLU, or a mixture of the two.


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