The effect of bilateral nephrectomy on the production and distribution of muramidase (lysozyme) in the rat

1970 ◽  
Vol 48 (2) ◽  
pp. 131-138 ◽  
Author(s):  
R. Keeler
Keyword(s):  
Kidney Tissue ◽  
High Plasma ◽  
Renal Tissue ◽  
Inhibitory Influence ◽  
Bilateral Nephrectomy ◽  
Venous Anastomosis ◽  
Rate Of Increase ◽  
Total Body ◽  
High Level

After bilateral nephrectomy total body muramidase in the rat increased by more than 50%. The mean rate of increase was 340 μg/h per 100 g. Skin and bone showed the greatest increase. Although the lungs contain a high level of muramidase there was no significant change in the level of enzyme activity after nephrectomy. Rats with sectioned ureters or with a uretero–venous anastomosis did not develop high plasma levels of muramidase. The response to nephrectomy is therefore not a response to uremia. Pretreatment of the animals with cortisone or DL-ethionine had no effect on the enzyme response to nephrectomy. This was taken to indicate that the response was not to antigenic material and did not depend upon hepatic synthesis of the enzyme. Pretreatment with the cytotoxic agent cyclophosphamide reduced the plasma and total body level of muramidase and blocked the response to nephrectomy. Direct measurement demonstrated a large increase in the rate of muramidase production by bone marrow. Since the in vitro inactivation of muramidase by kidney tissue could not be demonstrated, it is concluded that nephrectomy causes an increase in the rate of enzyme production rather than a failure of catabolism. Renal tissue might normally exert an inhibitory influence upon muramidase formation.

Evidence for a renal-dependent factor in the control of muramidase (lysozyme) formation

1969 ◽  
Vol 47 (9) ◽  
pp. 831-832 ◽  
Author(s):  
R. Keeler
Keyword(s):  
Bone Marrow ◽  
Plasma Flow ◽  
Enzyme Production ◽  
Fold Increase ◽  
Renal Tissue ◽  
Inhibitory Influence ◽  
Bilateral Nephrectomy ◽  
Total Body ◽  
Dependent Factor

After bilateral nephrectomy the total body muramidase in the rat increases by about 50% in 6 h. Since there was no evidence to suggest that this increase was the result of failure to remove or inactivate muramidase, experiments were performed to measure the rate of muramidase formation in the bone marrow of normal and nephrectomized rats. The enzyme production was measured as the product of the plasma flow and the arterio–venous difference. Results showed that 6 h after bilateral nephrectomy there was a 14-fold increase in muramidase production. It is suggested that renal tissue may normally exert an inhibitory influence upon muramidase formation.

Prolactin metabolism in the rat: role of the kidney in degradation of the hormone

1981 ◽  
Vol 240 (5) ◽  
pp. F437-F445 ◽  
Author(s):  
D. S. Emmanouel ◽  
V. S. Fang ◽  
A. I. Katz
Keyword(s):  
Glomerular Filtration ◽  
High Plasma ◽  
Metabolic Clearance ◽  
Bilateral Nephrectomy ◽  
Flow Conditions ◽  
Metabolic Clearance Rate ◽  
Kidney Perfusion ◽  
Organ Clearance

The contribution of impaired prolactin (PRL) degradation to the altered dynamics of this hormone in uremia was investigated in rats. Hyperprolactinemia developed after bilateral nephrectomy (BNx) or ligation of both ureters (BUL), whereas PRL levels remained normal in comparably azotemic animals undergoing urine autoinfusion in which glomerular filtration rate (GFR) was maintained. The renal organ clearance of PRL in control rats accounted for two-thirds of its metabolic clearance rate and was consistently less than GFR. Following BUL and BNx the metabolic clearance of PRL decreased predictably also by two-thirds. The importance of the renal parenchyma in the degradation of prolactin was confirmed during perfusion of isolated rat kidneys. Renal PRL handling involves mainly glomerular filtration and tubular reabsorption, although uptake from peritubular blood is also demonstrable under the high plasma flow conditions obtaining during in vitro kidney perfusion. We conclude that the hyperprolactinemia associated with acute uremia in the rat is not the consequence of the uremic state per se, but results from impaired renal degradation of the hormone.

scholarly journals THE DRUG-FASTNESS OF SPIROCHETES TO ARSENIC, MERCURIAL, AND IODIDE COMPOUNDS IN VITRO

1917 ◽  
Vol 25 (3) ◽  
pp. 349-362 ◽  
Author(s):  
Seinai Akatsu ◽  
Hideyo Noguchi
Keyword(s):  
Culture Media ◽  
Treponema Pallidum ◽  
Chemotherapeutic Agents ◽  
Inhibitory Influence ◽  
Fluid Medium ◽  
Rate Of Increase ◽  
Fluid Media ◽  
Pure Cultures ◽  
Free Media

In the foregoing experiments we attempted to determine whether or not, by subjecting several varieties of spirochetes to increasing doses of certain chemotherapeutic agents, a gradual increase of resistance to the latter could be shown. For this purpose, pure cultures of Treponema pallidum, Treponema microdentium, and Spirochœta refringens were used against the action of salvarsan, neosalvarsan, bichloride of mercury, and iodine-iodide potassium solution in vitro. For culture media, the usual ascites-broth-tissue medium as well as solid ascites-agar-tissue medium was used. After permitting the spirochetes to grow for a fortnight in media containing certain quantities of each drug, transfers were made from tubes showing various degrees of growth to the next series of tubes containing the same drug in still higher concentrations, and similar transfers repeated every 2 weeks. The results of the experiments may be briefly summarized as follows: 1. Treponema pallidum and Treponema microdentium have, within 3 to 4 months, increased their tolerance to salvarsan and neosalvarsan to five and one-half times their original mark. With Spirochata refringens the increase was about three times. 2. Against the action of bichloride of mercury, the amount of increased tolerance of Treponema pallidum was about 35 to 70 times the original, while that of Treponema microdentium was about 10 times as much and was reached within 10 weeks. Spirochata refringens resisted 30 times the original dose. 3. There was an unmistakable increase of resistance of these spirochetes to the action of the iodine-iodide solution (Lugol's solution) when they were grown for several generations in fluid media containing the iodine solution, but the rate of increase between the initial and the acquired tolerance was slight. In general, the addition of Lugol"s solution to fluid media has a weak inhibitory influence upon the growth of the spirochetes, requiring for the total suppression of growth a quantity of over 0.7 cc. to 5 cc. of the culture media. The tolerance reached was for about three times that amount. 4. A similar tolerance phenomenon has not been established when employing a solid instead of a fluid medium containing the drugs. No explanation is offered except a suggestion that the drugs held in the agar do not enter into combination with certain tissue constituents of the medium as they are able to do with tissue elements in fluid media. This may be a factor necessary for inducing drug tolerance in these organisms in vitro. 5. The increased drug-fastness in vitro has a limit beyond which no further advance can be made. This limit varies with different species of spirochetes. 6. The acquired drug-fastness in vitro gradually disappears when the spirochetes are cultivated again in the drug-free media for several generations.

Electron microscopic study of the membrane glycoproteins in the rat kidney after cisplatin treatment

1989 ◽  
Vol 47 ◽  
pp. 912-913
Author(s):  
S.K. Aggarwal
Keyword(s):  
Alkaline Phosphatase ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Kidney Tissue ◽  
Membrane Glycoproteins ◽  
Electron Microscopic ◽  
Before And After ◽  
Interstrand Cross Links ◽  
Cross Links

The proposed primary mechanism of action of the anticancer drug cisplatin (Cis-DDP) is through its interaction with DNA, mostly through DNA intrastrand cross-links or DNA interstrand cross-links. DNA repair mechanisms can circumvent this arrest thus permitting replication and transcription to proceed. Various membrane transport enzymes have also been demonstrated to be effected by cisplatin. Glycoprotein alkaline phosphatase was looked at in the proximal tubule cells before and after cisplatin both in vivo and in vitro for its inactivation or its removal from the membrane using light and electron microscopy.Outbred male Swiss Webster (Crl: (WI) BR) rats weighing 150-250g were given ip injections of cisplatin (7mg/kg). Animals were killed on day 3 and day 5. Thick slices (20-50.um) of kidney tissue from treated and untreated animals were fixed in 1% buffered glutaraldehyde and 1% formaldehyde (0.05 M cacodylate buffer, pH 7.3) for 30 min at 4°C. Alkaline phosphatase activity and carbohydrates were demonstrated according to methods described earlier.

In Vitro Effect of Chlorquine and Picroliv on Plasmodium Berghei Induced Alterations in the Activity of Adenosine Triphosphatase, Aryl Hyrocarbon Hydroxylase Enzymes and Malondialdehyde in spleen Explant Culture

2020 ◽  
Vol 20 ◽  
Author(s):  
Anchal Trivedi ◽  
Aparna Misra ◽  
Esha Sarkar ◽  
Anil K. Balapure
Keyword(s):  
Drug Resistance ◽  
Plasmodium Berghei ◽  
Adenosine Triphosphatase ◽  
Explant Culture ◽  
Need To Evaluate ◽  
Mda Content ◽  
High Level ◽  
Vitro Effect ◽  
Positive Effect

Background: In recent years, great progress has been made in reducing the high level of malaria suffering worldwide. There is a great need to evaluate drug resistance reversers and consider new medicines against malaria. There are many approaches to the development of antimalarial drugs. Specific concerns must be taken in to account in these approaches, in particular there requirement for very in expensive and simple use of new therapies and the need to limit drug discovery expenses. Important ongoing efforts are the optimisation of treatment with available medications, including the use of combination therapy. The production of analogs of known agents and the identification of natural products, the use of compounds originally developed against other diseases, the assessment of overcoming drug resistance and the consideration of new therapeutic targets. Liver and spleen are the important organs which are directly associated with malarial complications. Aim: An analysis the Activity of Adenosine Triphosphatase, Aryl Hyrocarbon Hydroxylase Enzymes and Malondialdehyde in spleen Explant Culture. Objective: To determine in-Vitro Effect of Chlorquine and Picroliv on Plasmodium Berghei Induced Alterations in the Activity of Adenosine Triphosphatase, Aryl Hyrocarbon Hydroxylase Enzymes and Malondialdehyde in spleen Explant Culture. Material and method: 1-Histological preparation of spleen explants for paraplast embedding 2-Biochemicalstudies (Enzymes (Atpase, ALP&GST) and the level of protein, Malondialdehyde (MDA). Result: Splenomegalyis one of the three main diagnostic parameters of malaria infection besides fever and anaemia. Many enzymes present in the liver and spleen may also be altered or liberated under different pathological conditions. Enzymes (ATPase, ALP&GST) and the level of protein, Malondialdehyde (MDA) content was found to increase in the liver and spleen explants during malarial infection. In the liver and spleen derived from parasitized CQ treated animals, the activity of all the above enzymes (ATPase, ALP&GST) and the level of protein & MDA of liver/spleen reversed towards the normal for all the 4or3 days of incubations. Picroliv efficacy decreased with the increment of parasitaemia and at 60%parasitaemia. Conclusion: Alkalinephosphatase (ALP) was found to increase with increasing parasitaemia. After the addition of Picroliv to the medium, a decrement in the activity was observed up to day 4 of culture.A similar positive effect of Picroliv was observed on the ATPase and ALP activity of spleen explants.DNA and protein contents also increased in the parasitized liver cultured in the presence of picroliv.On the contrary, in the spleen explants DNA, protein and MDA content were found to decrease after Picroliv supplementation to the culture medium.

scholarly journals Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01948-20
Author(s):  
Dalin Rifat ◽  
Si-Yang Li ◽  
Thomas Ioerger ◽  
Keshav Shah ◽  
Jean-Philippe Lanoix ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Evidence ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Wild Type ◽  
Content Type ◽  
Solid Media ◽  
High Level ◽  
Level Resistance

ABSTRACTThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5 CFU. Whole-genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, of which 91% occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance, namely, fbiC (56%), fbiA (15%), ddn (12%), fgd (4%), and fbiB (4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations in Rv2983 (fbiD), a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420 synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, although Rv2983 and fbiB mutants exhibited high-level pretomanid resistance but relatively small changes in delamanid susceptibility. Complementing an Rv2983 mutant with wild-type Rv2983 restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420 and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420 biosynthesis. Finally, Rv2983 mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.

scholarly journals Allelic Exchange and Mutant Selection Demonstrate that Common Clinical embCAB Gene Mutations Only Modestly Increase Resistance to Ethambutol in Mycobacterium tuberculosis

2009 ◽  
Vol 54 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Hassan Safi ◽  
Robert D. Fleischmann ◽  
Scott N. Peterson ◽  
Marcus B. Jones ◽  
Behnam Jarrahi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
In Vitro Selection ◽  
Gene Mutations ◽  
Wild Type ◽  
Mutant Selection ◽  
Preferential Growth ◽  
Allelic Exchange ◽  
High Level ◽  
Isogenic Mutants

ABSTRACT Mutations within codon 306 of the Mycobacterium tuberculosis embB gene modestly increase ethambutol (EMB) MICs. To identify other causes of EMB resistance and to identify causes of high-level resistance, we generated EMB-resistant M. tuberculosis isolates in vitro and performed allelic exchange studies of embB codon 406 (embB406) and embB497 mutations. In vitro selection produced mutations already identified clinically in embB306, embB397, embB497, embB1024, and embC13, which result in EMB MICs of 8 or 14 μg/ml, 5 μg/ml, 12 μg/ml, 3 μg/ml, and 4 μg/ml, respectively, and mutations at embB320, embB324, and embB445, which have not been identified in clinical M. tuberculosis isolates and which result in EMB MICs of 8 μg/ml, 8 μg/ml, and 2 to 8 μg/ml, respectively. To definitively identify the effect of the common clinical embB497 and embB406 mutations on EMB susceptibility, we created a series of isogenic mutants, exchanging the wild-type embB497 CAG codon in EMB-susceptible M. tuberculosis strain 210 for the embB497 CGG codon and the wild-type embB406 GGC codon for either the embB406 GCC, embB406 TGC, embB406 TCC, or embB406 GAC codon. These new mutants showed 6-fold and 3- to 3.5-fold increases in the EMB MICs, respectively. In contrast to the embB306 mutants, the isogenic embB497 and embB406 mutants did not have preferential growth in the presence of isoniazid or rifampin (rifampicin) at their MICs. These results demonstrate that individual embCAB mutations confer low to moderate increases in EMB MICs. Discrepancies between the EMB MICs of laboratory mutants and clinical M. tuberculosis strains with identical mutations suggest that clinical EMB resistance is multigenic and that high-level EMB resistance requires mutations in currently unknown loci.

scholarly journals Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Soft Agar ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Strong Positive Correlation ◽  
Cell Viability Assay ◽  
High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

Three-dimensional Growth of Renal Epithelial Cells in Vitro: A Tool in Toxicity Testing

1993 ◽  
Vol 21 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Knut-Jan Andersen ◽  
Erik Ilsø Christensen ◽  
Hogne Vik
Keyword(s):  
Epithelial Cells ◽  
Three Dimensional ◽  
Toxicity Testing ◽  
Renal Tissue ◽  
Epithelial Cell Line ◽  
Multicellular Spheroids ◽  
Renal Epithelial Cell ◽  
Renal Epithelial Cells

The tissue culture of multicellular spheroids from the renal epithelial cell line LLC-PK1 (proximal tubule) is described. This represents a biological system of intermediate complexity between renal tissue in vivo and simple monolayer cultures. The multicellular structures, which show many similarities to kidney tubules in vivo, including a vectorial water transport, should prove useful for studying the potential nephrotoxicity of drugs and chemicals in vitro. In addition, the propagation of renal epithelial cells as multicellular spheroids in serum-free culture may provide information on the release of specific biological parameters, which may be suppressed or masked in serum-supplemented media.

scholarly journals Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances

2021 ◽  
Vol 14 (7) ◽  
pp. 603
Author(s):  
Vanesa Pérez-Laguna ◽  
Isabel García-Luque ◽  
Sofía Ballesta ◽  
Antonio Rezusta ◽  
Yolanda Gilaberte
Keyword(s):  
Photodynamic Therapy ◽  
Soft Tissues ◽  
Combined Treatment ◽  
Resistance Pattern ◽  
Antimicrobial Photodynamic Therapy ◽  
Antimicrobial Drugs ◽  
Bacteria And Fungi ◽  
High Level ◽  
Selection Of

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent failure in the fight against these microorganisms: antimicrobial drugs can increase the susceptibility of microorganisms to aPDT and prevent the possibility of regrowth of those that were not inactivated during the irradiation; meanwhile, aPDT is effective regardless of the resistance pattern of the strain and their use does not contribute to the selection of antimicrobial resistance. Additive or synergistic antimicrobial effects in vitro are evaluated and the best combinations are presented. The use of combined treatment of aPDT with antimicrobials could help overcome the difficulty of fighting high level of resistance microorganisms and, as it is a multi-target approach, it could make the selection of resistant microorganisms more difficult.

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