scholarly journals Investigation on the Effect of Dose, Frequency and Duration of Allergen Exposure on Development of Staphylococcal Infections in a Chronic Model of Canine Atopic Dermatitis

2021 ◽  
Vol 9 (1) ◽  
pp. 8
Author(s):  
Rosanna Marsella

Canine atopic dermatitis (CAD) is chronic and frequently complicated by Staphylococcal infections. Understanding the role of allergen dose, frequency and duration of exposure in triggering infections requires a model. Most models elicit acute inflammation and do not mimic real-life disease. Here we describe the effects of allergen exposures on development of infections in a model of chronic CAD. Diagnosis of pyoderma was based on clinical signs and consistent cytology. Study 1 evaluated the role of duration of exposure keeping the daily dose constant (25 mg/day). The one-week protocol involved three exposures, 3 days in a row. The one-month protocol involved twice-weekly challenges for 4 weeks. The three-month protocol involved twice-weekly challenges for 12 weeks. Study 2 evaluated different daily doses while keeping constant the total weekly dose (25 mg) and duration (3 weeks). Low-dose used 5 mg/day for 5 days, each week. High-dose used 12.5 mg/day twice-weekly. In Study 1, the longer the exposure, the more dogs developed pyoderma (6/9 in the three-month study, 2/9 in the one-month and 0 in the one-week). In Study 2, low-dose daily exposure caused more infections (5/8) than high-dose infrequent exposure (0/8). It is concluded that low-grade, daily exposure for a long time is most relevant for development of staphylococcal infections.

2021 ◽  
Vol 10 (2) ◽  
pp. 294
Author(s):  
Atsushi Hosui ◽  
Takafumi Tanimoto ◽  
Toru Okahara ◽  
Munehiro Ashida ◽  
Kohsaku Ohnishi ◽  
...  

(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group (p < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration.


2011 ◽  
Vol 22 (4) ◽  
pp. 327-334 ◽  
Author(s):  
S. Meury ◽  
V. Molitor ◽  
M. G. Doherr ◽  
P. Roosje ◽  
T. Leeb ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 486
Author(s):  
Solène Marie ◽  
Irene Hernández-Lozano ◽  
Louise Breuil ◽  
Wadad Saba ◽  
Anthony Novell ◽  
...  

The multidrug resistance-associated protein 2 (MRP2) mediates the biliary excretion of drugs and metabolites. [99mTc]mebrofenin may be employed as a probe for hepatic MRP2 activity because its biliary excretion is predominantly mediated by this transporter. As the liver uptake of [99mTc]mebrofenin depends on organic anion-transporting polypeptide (OATP) activity, a safe protocol for targeted inhibition of hepatic MRP2 is needed to study the intrinsic role of each transporter system. Diltiazem (DTZ) and cyclosporin A (CsA) were first confirmed to be potent MRP2 inhibitors in vitro. Dynamic acquisitions were performed in rats (n = 5–6 per group) to assess the kinetics of [99mTc]mebrofenin in the liver, intestine and heart-blood pool after increasing doses of inhibitors. Their impact on hepatic blood flow was assessed using Doppler ultrasound (n = 4). DTZ (s.c., 10 mg/kg) and low-dose CsA (i.v., 0.01 mg/kg) selectively decreased the transfer of [99mTc]mebrofenin from the liver to the bile (k3). Higher doses of DTZ and CsA did not further decrease k3 but dose-dependently decreased the uptake (k1) and backflux (k2) rate constants between blood and liver. High dose of DTZ (i.v., 3 mg/kg) but not CsA (i.v., 5 mg/kg) significantly decreased the blood flow in the portal vein and hepatic artery. Targeted pharmacological inhibition of hepatic MRP2 activity can be achieved in vivo without impacting OATP activity and liver blood flow. Clinical studies are warranted to validate [99mTc]mebrofenin in combination with low-dose CsA as a novel substrate/inhibitor pair to untangle the role of OATP and MRP2 activity in liver diseases.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S216-S217
Author(s):  
Chao Ma ◽  
Yan Wu ◽  
Pei Chen ◽  
Yuan Jia ◽  
Dongqing Yin ◽  
...  

Abstract Background Our previous study indicated a therapeutic effect of Shi-Zhen-An-Shen-Tang (SZAST), a Chinese herb formula, on schizophrenia, but the related mechanism is unknown(citation). A large body of evidence suggests the important role of white matter of the brain in the pathophysiology of schizophrenia. This study was designed to evaluate the effect of SZAST on schizophrenia with demyelinated mice. Methods Male C57BL/6 mice were given mixed cuprizone (CPZ, a copper chelator, 0.2 %, w/w) rodent chow for six successive weeks to induce demyelination. During the last two weeks, mice were given an oral gavage of saline, or SZAST of three different doses (a low dose of 5.5g·kg-1·d-1, a medium dose of 8.24g·kg-1·d-1, or a high dose of 10.98 g·kg-1·d-1), or quetiapine, respectively. Behavioral tests were conducted after the last treatment. Meanwhile, the expression of myelin basic protein (MBP) and neuregulin-1(NRG1) in the brain was tested by immunohistochemistry staining or Western Blot. Results Mice exposed to CPZ for six weeks showed obvious schizophrenia-like behaviors, including lower nest-building activity, sensory gating activity, and higher locomotor activity. CPZ-fed mice also displayed a lower myelin density in the corpus callosum, hippocampus, and cerebral cortex and a reduction of MBP and NRG1 protein in the hippocampus compared with controls. Both quetiapine and SZAST significantly alleviated the abnormal schizophrenia-like behaviors and the impairment of myelin sheath in CPZ-fed mice, however, SZAST with medium dose showed better neuroprotective effect than the low dose or the high dose of SZAST. Furthermore, the expression of NRG1protein in the hippocampus was slightly, but not significantly increased in all SZAST-treated and quetiapine-treated groups. Discussion These results indicate that the neuroprotective effect of SZAST in demyelinated mice might partially relate to remyelination in the hippocampus in CPZ-fed mice.


1988 ◽  
Vol 254 (1) ◽  
pp. F134-F138 ◽  
Author(s):  
T. C. Welbourne ◽  
G. Givens ◽  
S. Joshi

Adrenalectomized (ADX) animals exhibit a blunted renal response to chronic acid loading. To determine whether this response truly reflects impaired renal ammoniagenesis from glutamine, urinary ammonium excretion was compared with acid intake in ADX, intact, and ADX rats supplemented with either a low dose (4 micrograms.100 g-1.day-1) or a high dose (40 micrograms.100 g-1.day-1) of triamcinolone. ADX rats consumed similar amounts of acid as did intact controls yet excreted only 37% of the load as ammonium; in contrast intact controls returned 86% and triamcinolone-supplemented animals returned 98 and 88% for low and high doses, respectively. Nor could the reduced ammonium excretion be attributed to increased renal venous release, since total ammonia production, the sum of renal venous and urine ammonium, was reduced to 49% of the intact controls; low- and high-dose triamcinolone restored and markedly increased the production rate. Underlying the impaired ammonia production rate in ADX rats was a reduced rate of glutamine extraction, 350 +/- 49 vs. 896 +/- 102 and 1,260 +/- 247 and 1,448 +/- 112 nmol.min-1.100 g-1 for intact and low and high doses, respectively. Unlike intact acidotic and glucocorticoid-supplemented ADX acidotic rats, glutamine extraction was disassociated from the delivered glutamine load consonant with the role of glucocorticoid in coupling cellular glutamine transport to its metabolic utilization.


2015 ◽  
Vol 26 (2) ◽  
pp. 95-e26 ◽  
Author(s):  
Petra Bizikova ◽  
Cherie M. Pucheu-Haston ◽  
Melissa N. C. Eisenschenk ◽  
Rosanna Marsella ◽  
Tim Nuttall ◽  
...  

2010 ◽  
Vol 60 (2-3) ◽  
pp. 183-196 ◽  
Author(s):  
Natalija Milcic-Matic ◽  
N. Popovic ◽  
M. Lazarevic ◽  
Ljiljana Medenica

2017 ◽  
Vol 7 (1) ◽  
pp. 9
Author(s):  
Edward B. Ilgren ◽  
John A. Hoskins

Anthophyllite asbestos only occurs in a few parts of the world in sufficient quantities to be mined. The largest deposits of anthophyllite asbestos occur in Finland where it was mined for more than 75 years and very extensively used and distributed, anciently, for more than six millennia. Anthophyllite is one of the five minerals known collectively as amphibole asbestos. Studies of the effect of these five mineral fibre types when inhaled have shown that fibre width is an important determinant of mesothelioma induction. Only the “thinner” fibres or those with fiber diameter dimensional profiles predominantly less than 0.25 – 0.30 µm, are clearly mesotheliogenic. The “thicker” ones or those whose predominant widths are greater than these diameters do not appear to show an observable attendant risk of mesothelioma. Observations based on studies of at least, two “thick” forms of amphibole asbestos support these hypotheses. The one is Bolivian crocidolite; the other Finnish anthophyllite. The Finnish anthophyllite industry presents an important opportunity to study the robustness of the theory that fibre width is key to mesothelioma genesis as vast numbers of people in all sectors of the Finnish industry and their families have historically incurred massive fiber exposures sufficient to cause a gross excess of asbestosis. Nonetheless, in spite of these long term, high dose exposures clear evidence for a mesothelioma risk due to anthophyllite asbestos is still lacking.


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