scholarly journals Single-Dose AmBisome (Liposomal Amphotericin B) as Prophylaxis for Murine Systemic Candidiasis and Histoplasmosis

2000 ◽  
Vol 44 (9) ◽  
pp. 2327-2332 ◽  
Author(s):  
April Garcia ◽  
Jill P. Adler-Moore ◽  
Richard T. Proffitt
Keyword(s):  
Single Dose ◽  
Amphotericin B ◽  
Histoplasma Capsulatum ◽  
Fungal Growth ◽  
Parent Drug ◽  
Control Group ◽  
High Dose ◽  
Prophylactic Efficacy ◽  
Immunocompetent Mice ◽  
Immunosuppressed Mice

ABSTRACT AmBisome is a liposomal formulation of amphotericin B that has broad-spectrum antifungal activity and greatly reduced toxicity compared to the parent drug. In this study, amphotericin B deoxycholate (Fungizone) (1 mg/kg) and AmBisome (1 to 20 mg/kg) were tested as single-dose prophylactic agents in both immunocompetent and immunosuppressed C57BL/6 mice challenged with either Candida albicans or Histoplasma capsulatum. Prophylactic efficacy was based on survival and fungal burden in the target organ (kidneys or spleen). At 9 to 10 days after histoplasma challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the control and Fungizone groups had died. All AmBisome-treated mice survived, although in the AmBisome groups given 1 mg/kg, the mice became moribund by day 10 to 12. No spleen CFU were detected in the histoplasma-challenged mice given 10 or 20 mg of AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal growth and/or death had occurred in all immunosuppressed mice except for four mice receiving 20 mg of AmBisome per kg. There were still no detectable fungi in the spleens of immunocompetent mice given 10 or 20 mg of AmBisome per kg. In the C. albicans experiment at 7 days postchallenge, all animals in both untreated and treated groups were alive with culture-positive kidneys. The kidney fungal burdens in AmBisome groups given 5 to 20 mg/kg were at least 1 log unit lower than those in the Fungizone group and significantly lower than those in the untreated control group (P < 0.05). There was a trend toward decreasing fungal growth in the kidneys as the dose of AmBisome was increased. In conclusion, these results show that a single high dose of AmBisome (5 to 20 mg/kg) had prophylactic efficacy in immunocompetent and immunosuppressed murine H. capsulatum and C. albicans models.

Ameliorative Effects of Quercetin in Cyclophosphamide-Induced Vascular Toxicity in Rats

2021 ◽  
Author(s):  
EMİN ŞENGÜL ◽  
VOLKAN GELEN ◽  
SEMİN GEDİKLİ ◽  
ELİF ERBAS ◽  
ASLIHAN ATASEVER
Keyword(s):  
Superoxide Dismutase ◽  
Single Dose ◽  
Corn Oil ◽  
Endothelial Damage ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Vascular Toxicity ◽  
Relaxation Responses

Abstract Cyclophosphamide (CYP) causes vascular toxicity and endothelial damage. In this study aimed the determination of the protective effects of Quercetin (Q) in the CYP-induced vascular toxicity in rats. The rats were randomly divided into the following five groups: Control, CYP, Q50+CYP, Q100+CYP and Q100. The control group was given intragastric (i.g.) corn oil for seven days. The CYP group received i.g. corn oil for seven days and a single dose (200 mg/kg) of CYP via intraperitoneal (i.p.) injection on the seventh day. The rats in the three Q-treated groups received Q for seven days. On the seventh day after the Q treatment, the Q50+CYP, and Q100+CYP groups were injected to single dose (200 mg/kg, i.p.) of CYP. The CYP-treatment both worsen the Phenylephrine (PE)-induced contractions and acetylcholine (ACh)-induced relaxation responses in isolated thoracic aorta of rats, and the application of Q corrected these responses. The malondialdehyde (MDA) levels were significantly higher in the CYP-treated groups. The both dose of Q decreased the MDA level. Superoxide dismutase (SOD) and glutathione (GSH) activities were significantly decreased in the CYP group, whereas the high dose of Q increased SOD and GSH activities. Q treatment attenuated CYP-induced pathologies, and endothelial damage. According to results, Q has protective effects against CYP-induced vascular toxicity in rats.

Comparison of fluconazole and amphotericin B in prophylaxis of experimental Candida endocarditis caused by non-C. albicans strains.

1996 ◽  
Vol 40 (2) ◽  
pp. 494-496 ◽  
Author(s):  
A S Bayer ◽  
M D Witt ◽  
E Kim ◽  
M A Ghannoum
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
Dose Regimen ◽  
Prophylactic Efficacy ◽  
Endocarditis Prophylaxis ◽  
Prophylactic Dose ◽  
Candida Strain ◽  
Fungistatic Agent

Amphotericin B (1 mg/kg of body weight, intravenous) and fluconazole (100 mg/kg, intraperitoneal) were compared in the prophylaxis of experimental Candida endocarditis caused by drug-susceptible, non-C. albicans strains C. tropicalis and C. parapsilosis. Neither antifungal agent was effective at preventing endocarditis due to either Candida strain when either agent was administered in a single-dose regimen (1 h prior to fungal challenge); the prophylactic efficacy of both agents increased substantially when a second prophylactic dose was given (24 h postchallenge). The excellent prophylactic efficacy of fluconazole, a fungistatic agent, underscores the importance of microbistatic mechanisms in endocarditis prophylaxis.

scholarly journals Observation on the clinical effect of high-dose Intravenous Immunoglobulin combined with low-dose prednisone acetate in the treatment of patients with Kawasaki Disease

2021 ◽  
Vol 37 (4) ◽  
Author(s):  
Hao Zhang ◽  
Mei-ying Wang ◽  
Yong-nan Teng ◽  
Xiao-dan Wang ◽  
Hai-tao Cao
Keyword(s):  
Single Dose ◽  
Kawasaki Disease ◽  
Low Dose ◽  
Clinical Effect ◽  
Pulse Therapy ◽  
Inflammatory Factors ◽  
Control Group ◽  
High Dose ◽  
Experimental Group ◽  
Dose Prednisone

Objective: To evaluate the clinical effect of high-dose intravenous immunoglobulin (HDIVIG) single dose and pulse therapy combined with small-dose prednisone acetate in the treatment of patients with Kawasaki disease (KD). Methods: Eighty patients with KD from Baoding Children’s Hospital, China, were randomly divided into two groups: the experimental group and the control group, each with 40 cases. Patients in the experimental group were treated with HDIVIG single dose, pulse therapy combined with low-dose prednisone acetate, while patients in the control group were treated with conventional-dose immunoglobulin. Patients in both groups were treated with aspirin orally, and given symptomatic treatment including anti-inflammatory, nutritional support, correction of water and electrolyte disturbance and acid-base balance. Peripheral venous blood samples were drawn from all patients at the time of admission, Day-1, Day-7 and Day-14 after treatment, and in the basic state of getting up in the morning, and then the levels of tumor necrosis factor (TNF-a), C-reactive protein (CRP), interleukin-6 (IL-6) and other inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The time of body temperature falling to normal, lymph node swelling recovery, hands and feet swelling, mucosal hyperemia regression after treatment in the two groups was recorded, and the treatment effect of the two groups was comprehensively evaluated. Results: After treatment, the levels of inflammatory factors such as TNF-a, CRP, IL-6 in the experimental group were significantly lower than those in the control group, with a statistically significant difference (P<0.05). In addition, the time of body temperature falling to normal, lymph node swelling recovery, hands and feet swelling, and mucosal hyperemia regression in the experimental group was significantly shorter than that in the control group (p=0.00). The effective rate of the experimental group was 95% and that of the control group was 80%, with a statistically significant difference (p=0.04). Conclusion: HDIVIG single dose, pulse therapy combined with small-dose prednisone acetate has a favourable therapeutic effect in the treatment of patients with KD, by which the inflammatory factors can be significantly improved, clinical symptoms and weight can be quickly ameliorated, and therapeutic effect can be enhanced. doi: https://doi.org/10.12669/pjms.37.4.4023 How to cite this:Zhang H, Wang MY, Teng YN, Wang XD, Cao HT. Observation on the clinical effect of high-dose Intravenous Immunoglobulin combined with low-dose prednisone acetate in the treatment of patients with Kawasaki Disease. Pak J Med Sci. 2021;37(4):---------. doi: https://doi.org/10.12669/pjms.37.4.4023 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Expression of Toll-Like Receptors (TLR2 and TLR4) in the Eyes of Mice with Disseminated Acanthamoebiasis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Karolina Kot ◽  
Danuta Kosik-Bogacka ◽  
Natalia Łanocha-Arendarczyk ◽  
Agnieszka Wojtkowiak-Giera ◽  
Agnieszka Kolasa-Wołosiuk
Keyword(s):  
Myeloid Leukemia ◽  
Control Group ◽  
Toll Like Receptors ◽  
Atypical Symptoms ◽  
Immunological Status ◽  
Bronchial Aspirate ◽  
Immunocompetent Mice ◽  
The Brain ◽  
Immunosuppressed Mice

Toll-like receptors (TLRs) play a key role in the innate immune response to numerous pathogens, including Acanthamoeba spp. The aim of this study was to determine the expression of TLR2 and TLR4 in the eyes of mice following intranasal infection with Acanthamoeba spp. in relation to the host’s immunological status. Amoebae used in this study were isolated from the bronchial aspirate of a patient with acute myeloid leukemia (AML) and atypical symptoms of pneumonia. We found statistically significant differences in the expression of TLR2 and TLR4 in the eye of immunocompetent mice at 8, 16, and 24 days after Acanthamoeba spp. infection (dpi) compared to control group. Immunosuppressed mice showed significant differences in the expression of TLR2 at 16 and 24 dpi compared to uninfected animals. Our results indicate that TLR2 and TLR4 are upregulated in the eyes of mice in response to Acanthamoeba spp. We suggest that it is possible for trophozoites to migrate through the optic nerve from the brain to the eyes. The course of disseminated acanthamoebiasis may be influenced by the host’s immunological status, and the observed changes in expression of TLR2 and TLR4 in the host’s organs may indicate the role of these receptors in the pathomechanism of acanthamoebiasis.

scholarly journals Comparison of a New Triazole, Posaconazole, with Itraconazole and Amphotericin B for Treatment of Histoplasmosis following Pulmonary Challenge in Immunocompromised Mice

2000 ◽  
Vol 44 (10) ◽  
pp. 2604-2608 ◽  
Author(s):  
Patricia Connolly ◽  
L. Joseph Wheat ◽  
Carol Schnizlein-Bick ◽  
Michelle Durkin ◽  
Steve Kohler ◽  
...  
Keyword(s):  
T Cells ◽  
Body Weight ◽  
Monoclonal Antibodies ◽  
Amphotericin B ◽  
Cd8 T Cells ◽  
Histoplasma Capsulatum ◽  
Study Groups ◽  
Immunocompetent Mice ◽  
Immunocompromised Mice ◽  
Fungal Colony

ABSTRACT A murine model of intratracheally induced histoplasmosis in immunocompromised B6C3F1 mice was used to evaluate a new triazole antifungal agent, posaconazole. This compound was previously shown to be comparable to amphotericin B and superior to itraconazole for the treatment of histoplasmosis in immunocompetent mice. The current study used mice that were depleted of T lymphocytes by intraperitoneal injection of anti-CD4 and anti-CD8 monoclonal antibodies beginning 2 days before infection and continuing at 5-day intervals until completion of the study. Groups of B6C3F1mice that were depleted of CD4 and CD8 T cells were infected with an inoculum of 104 Histoplasma capsulatum yeasts. All mice receiving posaconazole at 1 or 0.1 mg/kg of body weight/day, amphotericin B at 2 mg/kg every other day (qod), or itraconazole at 75 mg/kg/day survived to day 29. Only 60% of mice receiving itraconazole at 10 mg/kg/day and none receiving amphotericin B at 0.2 mg/kg qod survived to that date. Fungal burdens were determined at day 14 of infection, 1 day after discontinuation of therapy. Quantitative colony counts and Histoplasma antigen levels in lung and spleen tissues declined following treatment with amphotericin B at 2 mg/kg qod, posaconazole at 5 and 1 mg/kg/day, and itraconazole at 75 mg/kg/day but not in mice treated with amphotericin B at 0.2 mg/kg qod or itraconazole at 10 mg/kg/day. Posaconazole at 0.1 mg/kg/day reduced fungal colony counts and antigen levels in spleens but not in lungs. This study shows posaconazole activity for the treatment of histoplasmosis in immunosuppressed animals.

scholarly journals Treatment of Candida glabrata Infection in Immunosuppressed Mice by Using a Combination of Liposomal Amphotericin B with Caspofungin or Micafungin

2005 ◽  
Vol 49 (12) ◽  
pp. 4895-4902 ◽  
Author(s):  
Jon A. Olson ◽  
Jill P. Adler-Moore ◽  
P. J. Smith ◽  
Richard T. Proffitt
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Candida Glabrata ◽  
Systemic Infection ◽  
Sequential Therapy ◽  
The United States ◽  
Liposomal Amphotericin B ◽  
Control Group ◽  
Dose Dependent ◽  
Immunosuppressed Mice

ABSTRACT While Candida albicans remains the most common Candida isolate, Candida glabrata accounts for approximately 15 to 20% of all Candida infections in the United States. In this study we used immunosuppressed mice infected with C. glabrata to investigate the efficacy of liposomal amphotericin B alone or in combination with the echinocandin caspofungin or micafungin. For monotherapy, mice were given six daily doses of liposomal amphotericin B (3 to 20 mg/kg of body weight), caspofungin (1 to 5 mg/kg), or micafungin (2.5 to 10 mg/kg). With concomitant therapy, mice received liposomal amphotericin B (7.5 mg/kg) in addition to caspofungin (2.5 mg/kg) or micafungin (2.5 mg/kg) for 6 days. For sequential therapy, liposomal amphotericin B was administered on days 1 to 3 and caspofungin or micafungin was given on days 4 to 6; conversely, caspofungin or micafungin was administered on days 1 to 3 and liposomal amphotericin B was given on days 4 to 6. Efficacy was based on the number of CFU per gram of kidney 21 days postchallenge. Monotherapy with liposomal amphotericin B (7.5 to 20 mg/kg) was significantly more effective than no drug treatment (control group) (P < 0.05) and demonstrated a dose-dependent response, with 20 mg/kg lowering the CFU/g from 6.3 to 4.2 (significantly different from the value for the control group [P < 0.001]). Monotherapy with all echinocandin doses lowered the CFU/g from 6.0 to 6.4 to 2.7 to 3.3 (significantly different from the value for the control group [P < 0.001]) with no dose-dependent response. Complete clearance of infection could be achieved only when liposomal amphotericin B was given either concomitantly with caspofungin or micafungin or if liposomal amphotericin B was given sequentially with caspofungin. In conclusion, the combination of liposomal amphotericin B with an echinocandin markedly improved the therapeutic outcome in murine C. glabrata systemic infection.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Employing Gamma Ray Irradiated Giardia lamblia as Trialed Vaccine in Experimental Animal

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Amal Kamil Abdul Sada ◽  
Amany Mohamed Al-Kaysi
Keyword(s):  
Giardia Lamblia ◽  
Gamma Ray ◽  
Age Groups ◽  
Active Phase ◽  
Study Groups ◽  
Negative Control ◽  
Control Group ◽  
High Dose ◽  
Histopathological Changes ◽  
Gamma Irradiated

This is an experimental trial to prepare a vaccine from gamma-irradiated Giardia lamblia which is evaluated in experimental animals. The study was conducted from December 2015 to April 2016. The field survey of the parasite was conducted from those patients attending the laboratories of the Alawi Children's Hospital in Rusafa and the Al-Yarmouk Teaching Hospital in Karkh, through which 1250 stool samples of different age groups were examined. Five groups of mice were used in the study; the first was injected with normal saline and considered as a negative control group, the second was injected with cystic form of non-irradiated Giardia lamblia and considered as a positive control group, whereas the other three groups were injected with gamma irradiated Giardia lamblia at three different doses 10, 15 and 25 rad respectively. Giardia lamblia was primarily cultivated in liver infusion agar for ten days to obtain the active phase. On the sixth day, the cystic phase was purified and standardized to be used in the infection of mice with or without the exposure of gamma rays. Mice showed high sensitivity to parasitic infestation, in the gamma non-irradiated and the irradiated with gamma 10 rad, and 15 rad irradiated groups which was 100%. The results expressed an excystation process of the depleted phases and the release of the feeder phases. The results of the three irradiated groups consisted of histopathological changes of the small, and the rectum by dissection after two weeks of infection, with intestine amputation lesions, as well as ulceration and inflammation of the inflammatory cells represented in small numbers of neutrophil, lymphocytes, and eosinophils. The presence of ulceration and fall of epithelial cells in the intestinal cavity has been shown, and different forms of the parasite have been observed. Mice which was injected with irradiated G lamblia at high dose (25 rad), not show and sensitivity to the challenge infection and no excystation of thy parasite had been done. After 2 wreaks, a comparison was achieved between all study groups in which no histopathological changes were noticed in the mice irradiated with dose of25 rad. After another two weeks, a challenge dose was given (un-attenuated G lamblia) and mice were dissected after another two weeks, no changes on the level of histopathology of intestinal tissue were noticed the results suggested that mice acquire an immunity against the parasite infection.

Liver, Kidney Function Tests and Oxidative Damage During and after Treatment of Salmonella typhimurium Infection in Experimental Local Rabbits

2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Mustafa Salah Hasan ◽  
Ayman Barzan Abdulgafor ◽  
Maher Saber Owain ◽  
Mohammed Ali Hussein ◽  
Qusay Mohammed Aboud ◽  
...  
Keyword(s):  
Single Dose ◽  
Oxidative Damage ◽  
Salmonella Typhimurium ◽  
Infected Group ◽  
Post Treatment ◽  
Kidney Damage ◽  
Control Group ◽  
Post Inoculation ◽  
Group 5 ◽  
Group 2

This study aimed to evaluate the liver, kidney damage caused by S. typhimurium and to estimate the oxidative damage in association with this bacteria. A highly virulent isolates of S. typhimurium were obtained from the department of internal and preventive medicine/ College of Veterinary Medicine/ University of Baghdad. A twenty five local rabbits of both genders with age range (2-4 months) weeks old were used for this study, the rabbits were divided randomly into five groups each group contains 5 rabbits :- group 1: drenched orally with 5 ml of normal saline and consider as control group, group 2: were drenched orally with (5 ml) suspension which contain (5��109 CFU) of Salmonella typhimurium and regarded as infected group, group 3 were drenched orally with (5 ml) suspension which have (5��109 CFU) of Salmonella typhimurium then treated with a single dose of gentamicin alone at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation), group 4 were drenched (5 ml) suspension having (5��109 CFU) of Salmonella typhimurium then treated with a single dose of Ca-EDTA alone at 40mg/kg orally after presence of signs (after 24hrs. post inoculation) and group 5 were drenched (5 ml) suspension that contain (5��109 CFU) of Salmonella typhimurium then treated with a single dose of combined gentamicin at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation) and Ca-EDTA 40mg/kg after presence of signs (after 24hrs. post inoculation).The results of biochemical profile showed a significant increase (p less than 0.05) in ALT, creatinine and urea levels in infected group as compared with control group, while, the treated groups especially group 5 showed a significant improvement in ALT, Urea and creatinine levels which returned to relative normal levels as compared with infected group after 96hrs. post treatment. Also, the results of oxidative stress showed a significant increase in the levels of MDA in G2, G3, G4 and G5 after 48 hrs. post treatment, while the level of GSH showed a significant decrease in the level at 48hrs., both were returned to relative normal levels after 96hrs.post treatment especially in group 5.In conclusion, S. typhimurium can causing liver and kidney damage which is manifested by increase ALT, Urea and Creatinine. Also, MDA and GSH is increased due to salmonellosis.

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