scholarly journals Long-term effects of acute cadmium exposure on testis immune privilege

2020 ◽  
Vol 11 (2) ◽  
pp. 180-185
Author(s):  
B. Deng ◽  
O. V. Pakhomov ◽  
G. A. Bozhok

Cadmium (Cd) is a widespread and non-biodegradable pollutant of great concern to human health. This element can affect cellular signal transduction and cell-to-cell interaction in the testis. Immune tolerance towards auto- and alloantigens is an important component of testis immunity. It is involved in spermatogenesis and hormone secretion. Plus, the immune tolerance may help to reveal the changes in testis immunity over a long period after Cd exposure. The current research was aimed at investigating the long-term effects of acute Cd exposure on testis immunity by means of elicitation of testicular immune cell composition shift induced by Cd. Cadmium chloride was intraperitoneally injected at 3 mg Cd/kg to mice. After that testis interstitial cells were stained with surface markers for leukocyte and lymphocyte subpopulations (CD45, CD11b, CD3, CD4, CD8, CD25) and analyzed cytofluorimetrically by week 4, 6, 8 and 12 after Cd administration (Cd group). To identify the delayed effects of cadmium on immune tolerance two groups of animals were subjected to intratesticular allotransplantation of neonatal testis (groups ITT and Cd+ ITT). One of the groups was administered with Cd four weeks before the transplantation (Cd+ITT group). I group served as a control that did not undergo any transplantation or Cd injection. For a better demonstration of the phenomenon of immunological tolerance of the testicles, an additional group (UKT group) was used which got grafts under the kidney capsule (non-immune privileged site).Investigation of the cell population showed that CD45+, CD11b+, CD4+, CD8+ cells were permanently present in testicular interstitial tissue in I group. Intratesticular testis transplantation increased the proportion of CD11b+ but did not have such a pronounced effect on CD8+ cells in ITT group. Moreover, the transplantation elevated CD4+ CD25+ cells known for their immunosuppressive property and promoted graft development by week 2 (histological data). Cd injection resulted in severe inflammation that quenched by week 4 (Cd and Cd+ ITT groups). This time point was chosen for transplantation in Cd+ ITT group. Such Cd pretreatment led to a high CD8+ cell proportion and to the delayed appearance of CD4+ CD25+ cells by week 2 (Cd+ ITTgroup). The finding is consistent with the impairment of graft development in Cd+ ITTgroup pretreated with Cd. Observation suggest that Cd pretreatment was associated with disproportion of interstitial immune cell populations which resulted in the impairment of immunoprotective function of the testis. The impairment of testis immunity showed itself only after several weeks of Cd administration, and only when the recipient testis immunity was provoked by alloantigens of donor testes.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3493-3493
Author(s):  
John S. Pixley ◽  
Jessica L. Skopal-Chase ◽  
Alireza Torabi ◽  
Mihai C. Cenariu ◽  
Anupama Bhat ◽  
...  

Abstract The therapeutic application of in utero hematopoietic stem cell (HSC) transplantation (IUHSCT) is theoretically attractive for definitive treatment of congenital disease states. Investigating this technique in sheep, we have previously shown long-term engraftment and expression of both allogeneic and xenogeneic donor cells without cytoablation and, under appropriate conditions, without GVHD. The theoretical basis for IUHSCT is the well-recognized immune receptivity of the fetus to engraftment of donor cells. Engraftment and long-term expression of donor human and allogeneic sheep HSC reliably occur in the fetal sheep model if the IUHSCT is performed prior to day 71 of gestation (term: 145 days), during the period of presumed immuno-naïveté. Investigations using alternate animals have also noted that gestational age at transplantation is critical to achieving long-term engraftment, presumably as a result of inducing durable immune tolerance to the donor. Despite this presumption, however, the biologic explanation for fetal receptivity to donor engraftment and subsequent long-term tolerance following transplantation early in gestation is not known. In the present studies, we investigated the role fetal immune ontogeny plays in the induction of tolerance following IUHSCT in sheep. To this end, we performed parallel experiments examining engraftment receptivity of fetal sheep to allogeneic and xenogeneic HSC and the appearance of immune phenotypes in fetal sheep lymphoid organs at varying gestational ages (days 39 to birth), attempting to draw correlations between the appearance/absence of specific immune cells and the ability to achieve durable engraftment and immune tolerance. Engraftment receptivity was determined 60 days post-transplantation at different time points in sheep fetal gestation, while immune phenotypes were determined by flow cytometry using commercially available antibodies to immune cell surface markers. Our results indicate that the fetus is largely non-receptive to engraftment of both allogeneic and xenogeneic donor HSC prior to day 52 gestation and possesses a peak in engraftment receptivity between days 64–71 of gestation, which rapidly declines thereafter. With respect to the developing fetal immune system, the period of peak engraftment receptivity was associated with the expression of CD45 on all cells in the thymus. Double-positive and single-positive CD4 and CD8 cells began appearing in the thymus just prior (day 45 of gestation) to the beginning of the engraftment window, while single-positive CD4 or CD8 cells did not begin appearing in peripheral organs until late in the engraftment period, suggesting deletional mechanisms predominate during this time. In a similar fashion, surface IgM (sIgM)+ cells in the thymus were the first to express CD45, commencing expression around day 45 of gestation, with a comparable delay in the appearance of IgM+/CD45+ cells in the peripheral blood and spleen until late in the engraftment window. These findings support a central role for the thymus in multilineage immune cell maturation during the period of fetal transplantation receptivity. Further, they suggest that fetal engraftment receptivity/long-term engraftment and expression following IUHSCT is due to gestational age-dependent deletional tolerance. Further, our findings suggest that IUHSCT in humans may be more successful if performed during the comparable period in human gestation.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
L. Žalienė ◽  
D. Mockevičienė ◽  
B. Kreivinienė ◽  
A. Razbadauskas ◽  
Ž. Kleiva ◽  
...  

Aim. To evaluate the effects of riding for beginners (short-term) and advanced (long-term) riders with cerebral palsy on their whole mobility. The study involved 15 subjects (two girls and eleven boys). The subjects were aged from 3 to 19 years (8.73 years ± 5.85). All of the subjects had been diagnosed with a spastic form of cerebral palsy. The duration of the participation differed as follows: the advanced subjects had been riding for 1-4 years (2.66 years ± 1.16), while the beginners have been riding for two weeks (10 sessions). Group I (advanced riders) consisted of eight subjects (7 boys and 1 girl) who had therapy sessions regularly once a week and differed only in terms of the duration of their participation in the experiment. Group II (beginners) consisted of seven children (1 girl and 6 boys) who participated in only 10 riding sessions. All of the subjects were assessed according to the Gross Motor Function Measure (GMFM) and Gross Motor Function Classification System for CP (GMFCS) both before the investigation and after it. Conclusions. Ten riding lessons did not have an influence on the beginner riders with cerebral palsy gross motor functions and their gross motor function level did not change. However, in half of the advanced riders with cerebral palsy, the gross motor functions significantly improved. Meanwhile, the level of the performance of the gross motor skills in the four advanced riders increased, but this difference was not statistically significant.


1962 ◽  
Vol 24 (4) ◽  
pp. 453-NP ◽  
Author(s):  
M. ALLANSON ◽  
R. DEANESLY

SUMMARY Cadmium chloride, in a single subcutaneous injection, can destroy spermatogenic and interstitial cells in the rat testis (Pařízek, 1957) and produce changes in the pituitary. The interstitial tissue is restored by ingrowths from the tunica and full androgen secretion returns before there is any regeneration of germinal epithelium. A cytological study has been made of the peripheral and central pituitary gonadotrophs; the latter revert almost to normal as the interstitial tissue regenerates, whereas the former retain characteristic castration features, unless there is also regeneration of the germinal epithelium. This seems to indicate that in the normal testis there is a hormone contribution from the seminiferous tubules as well as from the interstitial cells. The long-term effects of cadmium on the testis depend on the dose. Early stages of tubule restoration have been studied, but after administration of 0·9 mg., actual proliferation of the germinal epithelium was rarely found—only in four out of twenty rats, 113 or 142 days after injection.


Shock ◽  
2019 ◽  
Vol 51 (6) ◽  
pp. 678-689 ◽  
Author(s):  
Yessica Alina Rodriguez-Rosales ◽  
Matthijs Kox ◽  
Esther van Rijssen ◽  
Bram van Cranenbroek ◽  
Marina van Welie ◽  
...  

2020 ◽  
Vol 10 (2) ◽  
pp. 98-106
Author(s):  
Mangge Zou ◽  
Juhao Yang ◽  
Carolin Wiechers ◽  
Jochen Huehn

AbstractListeria monocytogenes (Lm) is a food-borne pathogen with a high chance of infecting neonates, pregnant women, elderly and immunocompromised individuals. Lm infection in neonates can cause neonatal meningitis and sepsis with a high risk of severe neurological and developmental sequelae and high mortality rates. However, whether an acute neonatal Lm infection causes long-term effects on the immune system persisting until adulthood has not been fully elucidated. Here, we established a neonatal Lm infection model and monitored the composition of major immune cell subsets at defined time points post infection (p.i.) in secondary lymphoid organs and the intestine. Twelve weeks p.i., the CD8+ T cell population was decreased in colon and mesenteric lymph nodes (mLNs) with an opposing increase in the spleen. In the colon, we observed an accumulation of CD4+ and CD8+ effector/memory T cells with an increase of T-bet+ T helper 1 (Th1) cells. In addition, 12 weeks p.i. an altered composition of innate lymphoid cell (ILC) and dendritic cell (DC) subsets was still observed in colon and mLNs, respectively. Together, these findings highlight organ-specific long-term consequences of an acute neonatal Lm infection on both the adaptive and innate immune system.


2003 ◽  
Vol 27 (4) ◽  
pp. 260-267 ◽  
Author(s):  
ME Houdijk ◽  
MT Engelbregt ◽  
C Popp-Snijders ◽  
HA Delemarre van der Waal

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marya Kayyal ◽  
Tanvi Javkar ◽  
M. Firoz Mian ◽  
Dana Binyamin ◽  
Omry Koren ◽  
...  

Abstract There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning. We demonstrated that exposure to the antibiotic during the pre-weaning period led to long-term changes in social behaviour, but not anxiety-like traits, in male mice only. The change in behaviour of males was associated with decreased hippocampal expression of AVPR1A and AVPR1B while expression of both receptors was increased in females. Spleens of male mice also showed an increase in the proportion of activated dendritic cells and a corresponding decrease in regulatory T cells with penicillin exposure. All changes in brain, behaviour and immune cell populations, associated with penicillin exposure, were absent in mice that received L. rhamnosus JB-1 supplementation concurrent with the antibiotic. Our study indicates that post-natal exposure to a clinically relevant dose of antibiotic has long-term, sex dependent effects on the CNS and may have implications for the development of neuropsychiatric disorders. Importantly, we also provide further evidence that probiotic based strategies may be of use in counteracting detrimental effects of early-life antibiotics on neurodevelopment.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Babita Yadav ◽  
Amit Rai ◽  
Pallavi Suresh Mundada ◽  
Richa Singhal ◽  
B. C. S. Rao ◽  
...  

Abstract Objectives Primary Objective • To assess the efficacy of Ayurveda interventions and Yoga in rehabilitation of COVID-19 cases suffering with long term effects of COVID 19 as compared to WHO Rehabilitation Self-Management after COVID-19- Related Illness. Secondary Objective • To assess the safety of Ayurvedic interventions in cases suffering with long term effects of COVID 19 Trial design Multi-centric, randomized, controlled, parallel group, open-label, exploratory study. The study duration is 9 months and the intervention period is 90 days from the day of enrolment of the participant. Participants Patients of either sex between 18 to 60 years, ambulatory, willing to participate, with history (not more than 4 weeks) of positive RT-PCR for COVID-19 or IgM antibodies positivity for SARS CoV-2, but having negative RT-PCR for COVID-19 at the time of screening will be considered eligible for enrolment in the study. Critically ill patients with ARDS (acute respiratory distress syndrome), requiring invasive respiratory support in the intensive care unit, known case of any malignancy, immune-compromised state (e.g. HIV), diabetes mellitus, active pulmonary tuberculosis, past history of any chronic respiratory disease, motor neuron disease, multiple sclerosis, stroke, impaired cognition, atrial fibrillation, acute coronary syndrome, myocardial infarction, severe arrhythmia, concurrent serious hepatic disease or renal disease, pregnant or lactating women, patients on immunosuppressive medications, history of hypersensitivity to the trial drugs or their ingredients, depressive illness (before COVID-19), diagnosed psychotic illnesses, substance dependence or alcoholism will be excluded. The trial will be conducted at two medical colleges in Maharashtra, India. Intervention and comparator Intervention Arm (Group-I): Ayurveda interventions including Agastya Haritaki six gram and Ashwagandha tablet 500 mg twice daily orally after meals with warm water and two sessions of yoga (morning 30 minutes and evening 15 minutes) daily for 90 days, as per the post-COVID-19 care protocol provided in National Clinical Management Protocol based on Ayurveda and Yoga for management of COVID-19 published by Ministry of AYUSH, Government of India. Comparator Arm (Group-II): WHO Rehabilitation Self-Management after COVID-19 related illness for 90 days. The trial drugs are being procured from a GMP certified pharmaceutical company. Main outcomes Primary Outcome: Change in respiratory function to be assessed by San Diego shortness of breath Questionnaire, 6-minutes walk test and pulmonary function test. Secondary Outcomes: Change in High-resolution Computed Tomography (HRCT) Chest Change in Fatigue score assessed by Modified Fatigue Impact Scale Change in Anxiety score assessed by Hospital Anxiety and Depression Scale Score Change in Sleep Quality assessed by Pittsburgh Sleep Quality Index Change in the quality of life assessed by COV19-QoL scale Safety of the interventions will be assessed by comparing hematological and biochemical investigations before and after the intervention period and Adverse Event/ Adverse drug reaction Timelines for Outcome assessment Subjective parameters and clinical assessment will be assessed at baseline, 15th day, 30th day, 60th day and 90th day. Laboratory parameters (CBC, LFT, KFT, HbA1c, Hs-CRP, D-dimer), Pulmonary function test and HRCT Chest will be done at baseline and after completion of study period i.e. 90th day. Randomisation Statistical package for Social Sciences (SPSS) version 15.0 is used to generate the random number sequences. The participants will be randomized to two study groups in the ratio of 1:1. Blinding (masking) The study is open-label design. However, the outcome assessor will be kept blinded regarding the study group allocation of the participants. Numbers to be randomised (sample size) Sample size The sample size for the study is calculated assuming improvement in 6-minutes walk test by 40 meter in Group I and a change of 10 meter in Group II with a standard deviation of 50 meter based on the results of the previous studies, with 95% Confidence Level (α = 0.05) and 80% power and expecting a dropout rate of 20%. The number of participants to be enrolled in the study should be approximately 55 in each group. Hence, a total of 110 participants will be enrolled in the trial at each study site. Trial Status Participants’ recruitment started on 1st May 2021. Anticipated end of recruitment is August 2021. Protocol number: CCRAS-01 Protocol version number: 1.1, 13th January 2021. Trial registration The trial is prospectively registered with the Clinical Trial Registry of India (CTRI) on 03rd March 2021 [CTRI/2021/03/031686]. Full protocol The full protocol is attached as an additional file, accessible from the Journal website (Additional file 1). This communication serves as a summary of the key elements of the full protocol.


Author(s):  
Marie-Therese Heberer ◽  
Hubert C. Roggendorf ◽  
Franz-Josef Faber ◽  
Nicolai-Alexander Lawrenz ◽  
Roland Frankenberger ◽  
...  

Abstract Objectives The aim of this study was to investigate whether file design and taper significantly influence microcrack initiation during machine preparation. Materials and methods Sixty extracted teeth with straight single canals were selected. The teeth were randomly assigned to four groups based on their root canal anatomy and the corresponding NiTi rotary file system (I, Mtwo; II, ProTaper Universal; III, F6 SkyTaper; control, no preparation and filling). The root canals of the experimental groups were filled using the single-cone technique. The tested teeth were all subjected to a mechanical chewing simulation with flat lead loading over a period of 3 years (corresponding to 150,000 cycles). The teeth were checked for dentinal defects (accumulative crack growth in length) under the digital microscope (Keyence VHX-5000) at time 0 (baseline prior to chewing simulation) and after 3, 6, 12, 24, and 36 months of loading. The cumulative crack increase was statistically analyzed using the Kruskal–Wallis test, Jonckheere–Terpstra test, and the Wilcoxon rank-sum test. The significance was set at p < 0.05. Results In contrast to preparation with greater-tapered instruments, ProTaper Universal (group II) and F6 SkyTaper (group III) instrumentation with the smaller tapered Mtwo files (group I) showed less accumulative propagation of craze lines (p < 0.05) at all time points. Conclusion Instruments with greater taper for root canal instrumentation should be used with care to avoid negative long-term effects in the form of propagation of dentinal defects over time. A positive cutting-edge angle and a smaller taper have a positive effect on a lower craze line development. Clinical relevance Instruments with a positive cutting-edge angle and a smaller taper are beneficial for the long-term preservation of dentinal tooth structure.


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