Renal glutaminase adaptation and ammonia excretion in infant rats

1975 ◽  
Vol 228 (3) ◽  
pp. 693-698 ◽  
Author(s):  
S Benyajati ◽  
L Goldstein

The purpose of this investigation was to determine the role of enzyme adaptation in the response of ammonia excretion to acidosis in developing rats. The response of renal ammonia excretion was low in infant rats (7-12 days old) following administration of a single dose of acidifying salt (5 mmol NH4CL/kg). However, repeated administration (2 times daily) of the salt increased ammonia excretion two- to threefold within 2 days. This adaptive response was associated with a concomitant rise in renal phosphate-dependent glutaminase (PDG) activity; PDG activity increased from approximately 36% adult level in untreated infants to 79% adult level in infants given NH4Cl for 2 days. Ammonia excretion and PDG activity decreased in parallel following cessation of NH4Cl treatment. Administration of the antibiotic, actinomycin D (100 mug/kg, ip, 2 times daily for 2 days) completely inhibited the response of PDG to repeated NH4Cl administration. In contrast to the situation previously observed in adult rats, actinomycin D treatment prevented the acid-induced rise in renal ammonia excretion. These results suggest that the level of renal PDG plays a more direct role in the adaptation of ammonia excretion to acidosis in infant rats than in adults.

1997 ◽  
Vol 6 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Andrea Tuba ◽  
Mihály Kálmán

The present study focused on the early events of vascularization of intraocular cerebral transplants. Telencephalic pieces of rat embryos (El5) were transplanted into the anterior eye chamber of adult rats in deep ketamine-xylazine narcosis. At 3-, 4-, 5-, 6-, or 7-day postoperative survival periods, the rats were perfused and the transplants, with their iridic beds, were processed into serial, semi-thin sections, In 3- and 4-day transplants, neither dilated (perfused) nor collapsed blood vessels were found, but tissue defects, without proper wall and filled by non-nucleated (mature, host) erythrocytes, were seen. On post-operative day 5, large sinusoids were seen lines by endothel and free of blood cells (as a consequence of perfusion). On days 6 and 7, the usual, although large, blood vessels were found. Our results suggest that the critical period of transplant vascularization is between postoperative days 4 and 5, and that the original vessels of donor tissue degenerate and disappear during the first postoperative days and thus, do not participate directly in transplant vascularization. Our hypothesis is that vascular invasion begins with the opening of host blood vessels into clefts formed by degeneration of graft tissue. For a period, a hemostasis occurs in these blood-filled lacunae, and then endothel invasion from host vessels forms the proper wall. The transplant vasculature develops from these large sinusoids. The results challenge the role of the pre-existing donor vessels in transplant vascularization. A possible explanation of such paradoxical results is that the donor tissue must reach a stage of maturation to receive the ingrowing vessels, either host vessels, and the presence of vessels in the donor brain is the sign of this stage of maturation but has no direct role in transplant vascularization


2021 ◽  
Vol 22 (5) ◽  
pp. 2250
Author(s):  
Evita Athanasiou ◽  
Antonios N. Gargalionis ◽  
Fotini Boufidou ◽  
Athanassios Tsakris

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.


2021 ◽  
pp. 153568412110124
Author(s):  
Anna Reosti

This study illuminates an understudied pathway through which disadvantage is reproduced in the rental housing market: the housing search, application, and tenant screening process. Using in-depth interviews with 25 housing-seekers with criminal conviction records, past evictions, and damaged credit histories, this article examines the direct role of the rental housing search and application process in reproducing economic precarity and social disadvantage among renters with discrediting background records, beyond delimiting their housing options. Its findings suggest that navigating the housing search from a position of acute market disadvantage comes with significant costs for this population, including the financial burden of repeated application fees and the psychological strains associated with the specter of indefinite housing insecurity. The findings also demonstrate how the housing search process may undermine the willingness of stigmatized renters to contest exploitative or unlawful rental practices by reinforcing awareness of their degraded status in the rental market.


1984 ◽  
Vol 247 (3) ◽  
pp. G231-G239
Author(s):  
C. Gespach ◽  
Y. Cherel ◽  
G. Rosselin

Development of cAMP responses to secretin, pancreatic glucagon, and histamine was measured in gastric glands of fetal (day 20), postnatal (days 1-30), and adult rats (day 65). cAMP stimulation by these hormones was already detected on day 20 of gestation. cAMP generation showed biphasic variations during the 1st days of life and at the onset of weaning (day 20). Anticipated weaning at day 14 triggered precocious maturation (efficacies) of the cAMP-generating systems sensitive to secretin, glucagon, and histamine without changing the potencies of the hormones. During development, the general characteristics (potency and pharmacological or regulatory properties) of the receptor-cAMP systems studied were comparable with those evidenced in adult rats. At days 5, 20, and 65, vasoactive intestinal peptide and the peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) were about 100 times less potent than secretin (EC50 = 1.5 X 10(-9) M secretin). The histamine action could be blocked by the competitive H2-receptor antagonist cimetidine (70-100% inhibition) as well as by the noncompetitive inhibitor somatostatin (37-62% inhibition). The data indicate that these regulatory hormones (secretin, glucagon(s), histamine, and somatostatin) might have a direct effect on gastric glands and may modulate their biological activities (metabolism, differentiation, proliferation, and exocrine and endocrine secretions) from the neonatal period in rats. The important physiological role of weaning on the final maturation of the cAMP-generating systems in rat gastric glands is underlined.


2020 ◽  
Vol 129 (6) ◽  
pp. 1310-1323
Author(s):  
Jennifer L. Magnusson ◽  
Craig A. Emter ◽  
Kevin J. Cummings

The role of serotonin in arterial blood pressure (ABP) regulation across states of vigilance is unknown. We hypothesized that adult rats devoid of CNS serotonin (TPH2−/−) have low ABP in wakefulness and NREM sleep, when serotonin neurons are active. However, TPH2−/− rats experience higher ABP than TPH2+/+ rats in wakefulness and REM only, a phenotype present only in older males and not females. CNS serotonin may be critical for preventing high ABP in males with aging.


2012 ◽  
Vol 216 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Olivier Le Bacquer ◽  
Gurvan Queniat ◽  
Valery Gmyr ◽  
Julie Kerr-Conte ◽  
Bruno Lefebvre ◽  
...  

Regulated associated protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (rictor) are two proteins that delineate two different mTOR complexes, mTORC1 and mTORC2 respectively. Recent studies demonstrated the role of rictor in the development and function of β-cells. mTORC1 has long been known to impact β-cell function and development. However, most of the studies evaluating its role used either drug treatment (i.e. rapamycin) or modification of expression of proteins known to modulate its activity, and the direct role of raptor in insulin secretion is unclear. In this study, using siRNA, we investigated the role of raptor and rictor in insulin secretion and production in INS-1 cells and the possible cross talk between their respective complexes, mTORC1 and mTORC2. Reduced expression of raptor is associated with increased glucose-stimulated insulin secretion and intracellular insulin content. Downregulation of rictor expression leads to impaired insulin secretion without affecting insulin content and is able to correct the increased insulin secretion mediated by raptor siRNA. Using dominant-negative or constitutively active forms of Akt, we demonstrate that the effect of both raptor and rictor is mediated through alteration of Akt signaling. Our finding shed new light on the mechanism of control of insulin secretion and production by the mTOR, and they provide evidence for antagonistic effect of raptor and rictor on insulin secretion in response to glucose by modulating the activity of Akt, whereas only raptor is able to control insulin biosynthesis.


1987 ◽  
Vol 248 (2) ◽  
pp. 443-447 ◽  
Author(s):  
G J Beckett ◽  
S E Beddows ◽  
P C Morrice ◽  
F Nicol ◽  
J R Arthur

Selenium (Se) deficiency produced up to a 14-fold decrease in hepatic tri-iodothyronine (T3) production from thyroxine (T4) in vitro. The T3 production rate could not be restored by the addition of a variety of cofactors, nor by the addition of control homogenate. The impairment in hepatic T3 production observed in Se deficiency was reflected in the concentrations of thyroid hormones circulating in plasma, T4 being increased approx. 40% and T3 being decreased by 30%. However, the fall in plasma T3 concentrations was smaller than might be expected in view of the marked decreased in T3 production. Se deficiency had no measurable effect on plasma reverse-tri-iodothyronine concentrations. The data suggest that Se deficiency produces an inhibition of both 5- and 5′-deiodination, consistent with the widely held view that these reactions are catalysed by the same enzyme complex. The mechanism of inhibition appears not be mediated by changes in thiol levels, but a direct role of Se in the activity of the deiodinase complex cannot be excluded.


2021 ◽  
pp. 153537022199515
Author(s):  
Lídia Perea ◽  
Lorena Rodríguez-Rubio ◽  
Juan C Nieto ◽  
Carlos Zamora ◽  
Elisabet Cantó ◽  
...  

Bacteriophages are present in fluids from cirrhosis patients. However, their effect on the immune response is unknown. In this work, we explore the role of phages in the phenotype, function, and cytokine production of monocytes. We stimulated healthy monocytes with five different butanol-purified phage suspensions infective for Gram-negative and Gram-positive bacteria. We studied the expression of the monocyte markers involved in lipopolysaccharide recognition (LPS; CD14), antigen presentation (HLA-DR) and co-stimulation (CD86), and the concentration of induced cytokines (TNF-α, IFN-α, and IL-10) by phages. To confirm the direct role of phages without the interference of contaminating soluble LPS in phage suspensions, polymyxin B was added to the cell cultures. Phagocytosis experiments were assessed by flow cytometry using labeled phage suspensions. We observed that butanol-purified phages reduced the surface levels of CD14 and CD86 in monocytes and increased the secreted levels of TNF-α and IL-10 compared with the control sample containing only butanol buffer. All phage suspensions showed downregulation of HLA-DR expression but only Staphylococcus aureus phage contaminated with Escherichia coli reached statistical significance. The addition of polymyxin B did not restore the monocytic response induced by phages, suggesting that the effect was not caused by the presence of LPS. Monocytes were able to phagocyte phages in a dose- and time-dependent manner. To conclude, the phagocytosis of butanol-purified phages altered the phenotype and cytokine production of monocytes suggesting they become tolerogenic.


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