Dose-dependent viremia and the differential immunoglobulin response of hamsters to Powassan virus

1972 ◽  
Vol 18 (5) ◽  
pp. 655-661 ◽  
Author(s):  
Max A. Chernesky ◽  
Patricia J. Whittaker-Haines
Keyword(s):  
Neutralizing Antibodies ◽  
Low Dose ◽  
Gamma Globulin ◽  
High Dose ◽  
Post Inoculation ◽  
Anamnestic Response ◽  
Powassan Virus ◽  
Antibody Titers ◽  
Density Analysis ◽  
Dose Dependent

Hamsters injected subcutaneously with a single "low-dose" inoculum (10 mouse LD50) of Powassan virus developed viremia titering 106.2 mouse LD50 per milliliter of blood whereas hamsters receiving a "high-dose" inoculum of 105.0 mouse LD50 of virus developed a viremia of only 104.5 mouse LD50 per milliliter.Hemagglutination-inhibiting (HI) antibodies were first detected 7 days following the "low-dose" inoculation and attained maximum titers of 160. The HI antibody response to the "high-dose" virus inoculation began on the 5th day, at a time when viremia was present, and antibody titers did not exceed 40. Sucrose-density analysis and 2-mercaptoethanol treatment of sera revealed that IgM antibodies were induced by both inocula but animals receiving a low dose of virus produced higher IgG responses than did animals receiving a high dose of virus. Neutralizing antibodies, which did not appear until 30 days post inoculation, were present at a log neutralizing index (NI) of 2.0 at 60 days in animals receiving 10 mouse LD50 of virus and at a log NI of 1.0 in those receiving 105.0 mouse LD50. The NI of IgG was equal to the index for total gamma globulin in samples that contained both IgM and IgG as demonstrated by the HI test.Animals originally exposed to a "low-dose" inoculum produced a more prolonged anamnestic response when challenged 63 days later with 105.0 mouse LD50 of virus than did animals receiving a second inoculum containing only 103.0 or 10 mouse LD50 of virus. In contrast, poor secondary antibody responses were elicited by challenge doses of 105.0, 103.0, or 10 mouse LD50 of virus in animals that originally had received a "high-dose" of virus. IgM and IgG classes of antibody were induced in all secondary responses and the log NI of each group of animals was elevated by about 1 during anamnesis.

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg
Keyword(s):  
Low Dose ◽  
Matched Control ◽  
Control Group ◽  
High Dose ◽  
Withdrawal Therapy ◽  
The Mean ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

scholarly journals Serological response to rabies virus induced by commercial vaccines in cattle

2017 ◽  
Vol 47 (10) ◽  
Author(s):  
Mathias Martins ◽  
João Motta de Quadros ◽  
Eduardo Furtado Flores ◽  
Rudi Weiblen
Keyword(s):  
Rabies Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Dose ◽  
Booster Vaccination ◽  
Serological Response ◽  
Serum Samples ◽  
Anamnestic Response ◽  
Post Vaccination ◽  
Antibody Titers ◽  
One Year

ABSTRACT: The antibody response to rabies virus (RABV) induced by commercial vaccines in heifers was investigated. For this, 84 heifers were vaccinated twice (30 days interval) with each of four vaccines (G1 = 14 animals; G2 = 24; G3 = 22 and G4 = 24) and received a booster vaccination 360 days later. Serum samples collected at different intervals after vaccination and 30 days after booster were submitted to a virus neutralizing (VN) assay for RABV antibodies. Thirty days after the second vaccine dose, 92% of the immunized animals presented VN titers ≥0.5UI/mL (geometric medium titers [GMT] 1.7 to 3.8UI/mL). At the day of the booster (360 days post-vaccination); however, the percentage of animals harboring antibody titers ≥0.5UI/mL had dropped to 31% (0-80% of the animals, depending on the vaccine), resulting in lower GMT (0.1 to 0.6UI/mL). Booster vaccination at day 360 resulted in a detectable anamnestic response in all groups, resulting in 83% of animals (65 to 100%) harboring VN titers ≥0.5UI/mL thirty days later (GMT 0.6 to 4.3UI/mL). These results indicated that these vaccines were able to induce an adequate anti-RABV response in all animals after prime vaccination (and after booster as well). However, the titers decreased, reaching titers <0.5UI/mL in approximately 70% of animals within the interval before the recommended booster. Thus, booster vaccination for rabies in cattle using the current vaccines should be performed before the recommended one-year interval, as to maintain neutralizing antibodies levels in most vaccinated animals.

scholarly journals Major Depressive Disorder (MDD) and Antidepressant Medication Are Overrepresented in High-Dose Statin Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Leutner Michael ◽  
Matzhold Caspar ◽  
Kautzky Alexander ◽  
Kaleta Michaela ◽  
Thurner Stefan ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Inpatient Care ◽  
Low Dose ◽  
Antidepressant Medication ◽  
Statin Treatment ◽  
High Dose ◽  
Major Depressive ◽  
Dependent Relationship ◽  
Different Types ◽  
Dose Dependent

Objective: To examine the dose-dependent relationship of different types of statins with the occurrence of major depressive disorder (MDD) and prescription of antidepressant medication.Methods: This cross-sectional study used medical claims data for the general Austrian population (n = 7,481,168) to identify all statin-treated patients. We analyzed all patients with MDD undergoing statin treatment and calculated the average defined daily dose for six different types of statins. In a sub-analysis conducted independently of inpatient care, we investigated all patients on antidepressant medication (statin-treated patients: n = 98,913; non-statin-treated patients: n = 789,683). Multivariate logistic regression analyses were conducted to calculate the risk of diagnosed MDD and prescription of antidepressant medication in patients treated with different types of statins and dosages compared to non-statin-treated patients.Results: In this study, there was an overrepresentation of MDD in statin-treated patients when compared to non-statin-treated patients (OR: 1.22, 95% CI: 1.20–1.25). However, there was a dose dependent relationship between statins and diagnosis of MDD. Compared to controls, the ORs of MDD were lower for low-dose statin-treated patients (simvastatin&gt;0– &lt; =10 mg:OR: 0.59, 95% CI: 0.54–0.64; atorvastatin&gt;0– &lt; =10 mg:OR:0.65, 95%CI: 0.59–0.70; rosuvastatin&gt;0– &lt; =10 mg:OR: 0.68, 95% CI: 0.53–0.85). In higher statin dosages there was an overrepresentation of MDD (simvastatin&gt;40– &lt; =60 mg:OR: 2.42, 95% CI: 2.18–2.70, &gt;60–80 mg:OR: 5.27, 95% CI: 4.21–6.60; atorvastatin&gt;40– &lt; =60 mg:OR: 2.71, 95% CI: 1.98–3.72, &gt;60– &lt; =80 mg:OR: 3.73, 95% CI: 2.22–6.28; rosuvastatin&gt;20– &lt; =40 mg:OR: 2.09, 95% CI: 1.31–3.34). The results were confirmed in a sex-specific analysis and in a cohort of patients taking antidepressants, prescribed independently of inpatient care.Conclusions: This study shows that it is important to carefully re-investigate the relationship between statins and MDD. High-dose statin treatment was related to an overrepresentation, low-dose statin treatment to an underrepresentation of MDD.

Calcitriol Exerts Prophylactic Anti-Mycobacterium Effect In A Dose-Dependent Manner

2021 ◽  
Author(s):  
Jianguo Li ◽  
Zhen Li ◽  
Zefeng Gao ◽  
Juan Xia ◽  
Jia Cui ◽  
...  
Keyword(s):  
Vitamin D ◽  
1H Nmr ◽  
Low Dose ◽  
Bacterial Load ◽  
High Dose ◽  
Dependent Manner ◽  
Prophylactic Effect ◽  
Moderate Dose ◽  
Metabolism Pathway ◽  
Dose Dependent

Abstract Vitamin D was empirically applied for Tuberculosis (TB) treatment in the past, and is currently used as an adjuvant for TB therapy. Although an increasing pile of evidences suggests that vitamin D has no therapeutic effect against TB infection, the prophylactic effect of vitamin D in preventing TB remains largely undetermined. To experimentally valuate the potential prophylactic effect of calcitriol (the active form of vitamin D) against mycobacterium infection, we performed dose-gradient calcitriol soaking in 30-day-old zebrafish before Mycobacterium marinum (M. marinum) challenge through tail vein injection. 1H-NMR metabolomics analysis was further performed for illustration of potential mechanisms underlying the prophylactic effect of calcitriol against M. marinum. The results suggested that calcitriol exerts dose-dependent prophylactic anti-mycobacterium effects, i.e., the bacterial load and the corresponding inflammatory factors (IL-1β, TNF-α, and IFN-γ) expressions in M. marinum challenged zebrafish were reduced by low-dose (25 µg/L) or high-dose (2500 µg/L) calcitriol soaking, rather than by moderate-dose (250 µg/L) calcitriol soaking. Body weight of the M. marinum challenged zebrafish was recovered by high-dose prophylactic calcitriol soaking rather than by low-dose or moderate-dose calcitriol. The 1H-NMR metabolomic profiling identified 29 metabolites with altered abundance among the dose-gradient calcitriol groups, among which 22 metabolites were co-varied with the dose of calcitriol, the rest 7 metabolites were co-varied with the bacterial load and the inflammatory response in term of cytokine expression. Further pathway analysis indicated that the glycine, serine, and threonine metabolism pathway was the activated in both of the two metabolite groups, indicating that the pathway was altered by dose-gradient of calcitriol and was in response to M. marinum infection in zebrafish. The results of the present study suggested that the activation of glycine, serine and threonine metabolism pathway may play a potential role for the dose-dependent anti-mycobacterium effect induced by prophylactic calcitriol soaking.

scholarly journals Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yong Xie ◽  
Meng Pan ◽  
Yanpan Gao ◽  
Licheng Zhang ◽  
Wei Ge ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Low Dose ◽  
High Dose ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
High Dose Aspirin

AbstractThe failure of remodeling process that constantly regenerates effete, aged bone is highly associated with bone nonunion and degenerative bone diseases. Numerous studies have demonstrated that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) activate cytokines and mediators on osteoclasts, osteoblasts and their constituent progenitor cells located around the remodeling area. These cells contribute to a complex metabolic scenario, resulting in degradative or synthetic functions for bone mineral tissues. The spatiotemporal effects of aspirin and NSAIDs in the bone remodeling are controversial according the specific therapeutic doses used for different clinical conditions. Herein, we review in vitro, in vivo, and clinical studies on the dose-dependent roles of aspirin and NSAIDs in bone remodeling. Our results show that low-dose aspirin (< 100 μg/mL), which is widely recommended for prevention of thrombosis, is very likely to be benefit for maintaining bone mass and qualities by activation of osteoblastic bone formation and inhibition of osteoclast activities via cyclooxygenase-independent manner. While, the roles of high-dose aspirin (150–300 μg/mL) and other NSAIDs in bone self-regeneration and fracture-healing process are difficult to elucidate owing to their dual effects on osteoclast activity and bone formation of osteoblast. In conclusion, this study highlighted the potential clinical applications of low-dose aspirin in abnormal bone remodeling as well as the risks of high-dose aspirin and other NSAIDs for relieving pain and anti-inflammation in fractures and orthopedic operations.

scholarly journals Intravenous administration of sodium propionate induces antidepressant or prodepressant effect in a dose dependent manner

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chunyan Hao ◽  
Zefeng Gao ◽  
XianJun Liu ◽  
Zhijiang Rong ◽  
Jingjing Jia ◽  
...  
Keyword(s):  
Body Weight ◽  
Low Dose ◽  
Antidepressant Effect ◽  
High Dose ◽  
Mild Stress ◽  
Dependent Manner ◽  
Reward Seeking ◽  
Metabolomic Profiling ◽  
Hydroxyanthranilic Acid ◽  
Dose Dependent

AbstractPropionate has been reported to exert antidepressant effects, but high-dose propionate may induce autism-like symptoms in experimental animals through induction of dysbiosis of neurotransmitters. The bi-directional effects of propionate seem to be dose-dependent. However, due to the pathological discrepancies between depression and autism, conclusions drawn from autism may not be simply transferable to depression. The effect and underlying action mechanisms of high-dose propionate on depression remains undetermined. To investigate the effects of propionate on depression, propionate dose gradients were intravenously administrated to rats exposed to chronic unpredictable mild stress (CUMS) for 1 week. Results of these behavioral tests demonstrate that low-dose propionate (2 mg/kg body weight/day) induces antidepressant effect through bodyweight recovery, elevated reward-seeking behaviors, and reduced depression-like behaviors, while high-dose propionate (200 mg/kg body weight/day) induces prodepressant effects opposite of those of low-dose propionate. A comprehensive profiling of neurotransmitters in the hippocampus demonstrated that CUMS induces reduction of NE (Norepinephrine), DA (Dopamine). GABA (γ-aminobutyric acid) was recovered by low-dose propionate, while high-dose propionate exerted more complicated effects on neurotransmitters, including reduction of NE, DA, 5-Hydroxytryptamine and Tryptophan, and increase of GABA, Kynurenine, Homovanillic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine. The neurotransmitters disturbed by high-dose propionate suggest metabolic disorders in the hippocampus, which were confirmed by the clear group separation in PCA of metabolomic profiling. The results of this study demonstrate the double-edged dose-dependent effects of propionate on depression and suggest potential cumulative toxicity of propionate as a food additive to mood disorders.

A Randomized Dose-Escalating Phase I Trial of a Replication-Deficient Lymphocytic Choriomeningitis Virus Vector-Based Vaccine Against Human Cytomegalovirus

2020 ◽  
Author(s):  
Michael Schwendinger ◽  
Georges Thiry ◽  
Beatrice De Vos ◽  
Geert Leroux-Roels ◽  
Jacques Bruhwyler ◽  
...  
Keyword(s):  
Phase I ◽  
Human Cytomegalovirus ◽  
Neutralizing Antibodies ◽  
Phase I Trial ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
High Dose ◽  
Double Blind ◽  
High Fraction ◽  
Dose Dependent

Abstract Background A vaccine (HB-101) consisting of 2 nonreplicating lymphocytic choriomeningitis virus (LCMV) vectors expressing the human cytomegalovirus antigens glycoprotein B (gB) and the 65-kD phosphoprotein (pp65), respectively, is in development to prevent cytomegalovirus infection. Methods HB-101 was tested in cytomegalovirus-naive, healthy adults in a randomized, double-blind, placebo-controlled, dose-escalation Phase I trial. Fifty-four subjects received low, medium, or high dose of HB-101 or placebo by intramuscular administration at Month 0, 1, and 3. Safety and immunogenicity were the respective primary and secondary endpoints. Subjects were followed for 12 months after the initial immunization. Results Vaccination was associated with transient mild to moderate adverse events. HB-101 administration induced dose-dependent gB- and pp65-specific cellular responses, dominated by pp65-specific CD8 T cells, a high fraction of which were polyfunctional. Two administrations were sufficient to elicit dose-dependent gB-binding and cytomegalovirus-neutralizing antibodies (Abs). Cytomegalovirus-specific immune responses were boosted after each administration. Only 1 of 42 vaccine recipients mounted a transient LCMV vector-neutralizing Ab response. Conclusions HB-101 was well tolerated and induced cytomegalovirus-specific polyfunctional CD8 T-cell and neutralizing Ab responses in the majority of subjects. Lack of vector-neutralizing Ab responses should facilitate booster vaccinations. These results justify further clinical evaluation of this vaccine candidate.

Phase Ib dose-escalation study of Pexa-Vec (pexastimogene devacirepvec; JX-594), an oncolytic and immunotherapeutic vaccinia virus, administered by intravenous (IV) infusions in patients with metastatic colorectal carcinoma (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3608-3608 ◽  
Author(s):  
Jeeyun Lee ◽  
Young Suk Park ◽  
James Burke ◽  
Ho Yeong Lim ◽  
Jihye Lee ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Dose Escalation ◽  
Low Dose ◽  
High Dose ◽  
Pharmacokinetic Studies ◽  
Systemic Delivery ◽  
Dose Escalation Study ◽  
Gm Csf ◽  
Anti Tumor Activity ◽  
Dose Dependent

3608^ Background: Pexa-Vec is an EGFR-targeted vaccinia virus engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF), thereby stimulating direct oncolysis, tumor vascular disruption and anti-tumor immunity (Nat Rev Cancer 2009). Dose-dependent IV Pexa-Vec delivery was defined previously (Nature2011). This study was designed to assess the safety, maximal tolerated dose and anti-tumor activity of Pexa-Vec administered IV in patients with mCRC after failure of standard therapies. Methods: Nine patients were treated at 1 of 3 dose levels (106, 107 or 3x107pfu/kg IV every 2 weeks x 4) in a standard 3+3 dose-escalation design; 6 additional patients were enrolled at the MFD. Anti-tumor activity according to RECIST was determined using serial CT scans. Pharmacokinetic studies were also performed. Data summarized prior to database lock. Results: 15 patients with mCRC refractory to irinotecan, oxaliplatin, and 5-FU were treated (median lines of therapy 5; range 2-7); 13 of 15 received prior anti-angiogenic agents, and 11 of 12 KRAS WT tumors failed cetuximab. Adverse events were generally grade 1/2 and included: fever (93%), chills (93%), headache (60%), nausea (60%), and hypotension (40%). No dose-limiting toxicities or grade 3/4 events were reported. Only patients treated at high-dose (Cohort 3 & Expansion) exhibited a pustular rash (n=9; 78%). Pexa-Vec genomes detected in blood acutely were above the dose threshold for systemic delivery. Notably, clearance was not more rapid with repeated IV treatments despite the induction of humoral immunity. Furthermore, patients at the top dose level exhibited increased disease stabilization at Week 4 (89% high-dose (n= 9) versus 33% low-dose (n=6)). A trend (p=0.16) towards increased overall survival at high vs low-dose Pexa-Vec was observed with 78% high-dose patients still alive between 5 and 13 mos. Conclusions: Repeat IV Pexa-Vec was well-tolerated with transient flu-like symptoms. Dose-dependent safety, pharmacokinetics and anti-tumor activity were described in treatment-refractory mCRC patients. Clinical trial information: NCT01380600.

scholarly journals Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Tatsuya Hirose ◽  
Yasutaka Shinoda ◽  
Ayaka Kuroda ◽  
Aya Yoshida ◽  
Machiko Mitsuoka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Clinical Laboratory ◽  
Laboratory Data ◽  
High Dose ◽  
Clinical Effects ◽  
Efficacy And Safety ◽  
Watery Stool ◽  
Group 4 ◽  
Dose Dependent

Background. Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Patients and Methods. Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n=22) and high-dose (15 g DKT; n=11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Results. Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases (P<0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first (P=0.0133) and second (P=0.0101) weeks, respectively. There was no significant change in clinical laboratory values. Conclusion. We suggest that DKT increases defaecation frequency and is safe for treating constipation.

scholarly journals BLACK TEA INFUSION AMELIORATES ENZYMATIC CHANGES INDUCED BY SUBCUTANEOUS EXPOSURE OF GASOLINE AND GM-10 IN MICE

2015 ◽  
Vol 3 (9SE) ◽  
pp. 1-5
Author(s):  
Manjeet Dave ◽  
Ramtej Jayram Verma
Keyword(s):  
Low Dose ◽  
Succinic Dehydrogenase ◽  
Subcutaneous Administration ◽  
Black Tea ◽  
High Dose ◽  
Tea Infusion ◽  
Ameliorative Effect ◽  
Cervical Dislocation ◽  
Enzymatic Changes ◽  
Dose Dependent

The present study was carried out to examine the ameliorative effect of black tea infusion on gasoline and GM-10 induced enzymatic changes in kidney of mice. Eighty healthy adult Swiss strain male albino mice weighing 32-35 gm were divided into eight groups including untreated control and various treated groups. Treated groups were subcutaneously administered with gasoline (412 mg/kg/day) and GM-10 low dose (206 mg/kg/day) and high dose (412 mg/kg/day) for 30 days. Black tea infusion (2%) was orally administered alone and along with gasoline and GM-10 through drinking water. All experimental animals were sacrificed on 31st day by cervical dislocation; kidney were isolated and used. Activities of succinic dehydrogenase, adenosine triphosphatase, acid phosphatase and alkaline phosphatase were assayed in kidney.The results revealed that subcutaneous administration of gasoline and GM-10 caused dose-dependent, significant enzymatic alterations in kidney of mice. Oral administration of black tea infusion along with subcutaneous treatment with gasoline and GM-10 significantly ameliorates all enzymatic changes induced by gasoline and GM-10 in kidney of mice.

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