REACTIONS OF DRUG-DEPENDENT ANTIBODIES WITH METABOLITES OF QUININE (Qn) AND QUINIDINE (Qd)

1987 ◽  
Author(s):  
D J Christie ◽  
H Diaz-Arauzo ◽  
J M Cook
Keyword(s):  
Ring Structure ◽  
Quinoline Ring ◽  
Drug Induced ◽  
Group 3 ◽  
Methyl Derivatives ◽  
Drug Dependent ◽  
Group 2 ◽  
Asymmetric Carbon ◽  
Group 1

In many cases of drug-induced immunologic thrombocytopenia (DITP), a metabolite, rather than the native drug, is suspected of provoking the destructive drug-dependent antibodies (DDAB) responsible for this severe hemorrhagic disorder. However, this has not previously been investigated for Qn- and Qd-DDAB. We report evidence that the native drugs, and not their metabolites, are the provocative agents in Qn and Qd DITP. Reactions of Qn- and Qd-DDAB with platelets were studied with the native drugs and four of their metabolites: the N-oxide and 10,11-diol derivatives (quinuclidine ring modifications), the des-methyl derivatives (aromatic quinoline ring modification), and 2'-quininone and 2'-quinidinone (2'-oxo derivatives) (also quinoline ring modifications on Qn and Qd, respectively). Five antibodies were studied:two Group 1 DDAB (specific for compounds with native configuration at asymmetric carbon positions), two Group 2 DDAB (similar to Group 1 DDAB but also known to require the methoxy group on the quinuclidine ring for full activity), and one Group 3 DDAB (reactive with the native drug, its stereoisomer, and several nonmetabolic analogs of both compounds) . Using a complement-dependent 51Cr-lysis assay, the reactions of all DDAB with platelets and the four metabolites were similar to 100-fold weaker when compared to reactions obtained with the native drug, with these exceptions:Group 2 DDAB failed to react with the desmethyl and 2'-oxo metabolites and the Group 3 DDAB failed to react with 2'-oxo Qd. This observation shows that the activity of certain DDAB is critically dependent on the native quinoline ring structure. Importantly, none of the DDAB reacted more strongly with any of the metabolites tested when compared with reactions in the presence of the native drug. These findings indicate that DDAB react with platelets preferentially in the presence of the unaltered Qn and Qd molecules and suggest that, while the role of metabolites cannot be entirely ruled out, the native structure of the drug molecule is sufficient to stimulate production of the antibodies responsible for DITP.

P5392Epicardium derived cells promote sympathetic ganglionic outgrowth towards myocardium in vitro

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Ge ◽  
A M Smits ◽  
J C Van Munsteren ◽  
T Van Herwaarden ◽  
A M D Vegh ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Autonomic Innervation ◽  
Cardiac Damage ◽  
Group 4 ◽  
Group 3 ◽  
Cervical Ganglia ◽  
Group 2 ◽  
Group 1

Abstract Background The autonomic nerve system is essential to maintain homeostasis in the body. In the heart, autonomic innervation is important for adjusting the physiology to the continuously changing demands such as stress responses. After cardiac damage, excessive neurite outgrowth, referred to as autonomic hyperinnervation, can occur which is related to ventricular arrhythmias and sudden cardiac death. The cellular basis for this hyperinnervation is as yet unresolved. Here we hypothesize a role for epicardium derived cells (EPDCs) in stimulating sympathetic neurite outgrowth. Purpose To investigate the potential role of adult EPDCs in promoting sympathetic ganglionic outgrowth towards adult myocardium. Method Fetal murine superior cervical ganglia were dissected and co-cultured with activated adult mesenchymal epicardium-derived cells (EPDCs) or/and adult myocardium in a 3D collagen gel culture system. Four experiment groups were included: Group 1: Vehicle cultures (ganglia cultured without EPDC/myocardium) (n=48); Group 2: ganglia co-cultured with EPDCs (n=38); Group 3: ganglia co-cultured with myocardium (n=95); and group 4: ganglia co-cultured with both EPDCs and myocardium (n=96). The occurrence of neurite outgrowth was assessed in each group. The density of neurites that showed directional sprouting (i.e. sprouting towards myocardium) was assessed as well with a semi-automatic quantification method. Finally, sub-analyses were made by taking gender into account. Results Cervical ganglia cultured with EPDCs alone (group 2) showed increased neurite outgrowth compared to vehicle cultures (group 1), however the neurites did not show directional sprouting towards EPDCs. When co-cultured with myocardium (group 3), directional neurite outgrowth towards myocardium was observed. Compared to the ganglia-myocardium co-cultures, directional outgrowth was significantly increased in co-cultures combining myocardium and EPDCs (group 4), and the neurite density was also significantly augmented. Comparison between males and female ganglia demonstrated that more neurite outgrowth occurred in female-derived ganglia than in male-derived ganglia under the same co-culture conditions. Conclusion Activated adult EPDCs promote sympathetic ganglionic outgrowth in vitro. Sex differences exist in the response of ganglia to EPDCs, and female-derived ganglia appear more sensitive to EPDC-signalling. Results support a role of EPDCs in cardiac autonomic innervation and open avenues for exploring of their role in ventricular hyperinnervation after cardiac damage.

scholarly journals Odour-Evoked Memory in Dogs: Do Odours Help to Retrieve Memories of Food Location?

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1249
Author(s):  
Angelo Quaranta ◽  
Serenella d’Ingeo ◽  
Marcello Siniscalchi
Keyword(s):  
Learning Task ◽  
Spatial Task ◽  
Spatial Memories ◽  
Group 3 ◽  
Group 2 ◽  
Odor Group ◽  
With Memory ◽  
Specific Odor ◽  
Group 1

The ability of odors to spontaneously trigger specific memories has been widely demonstrated in humans. Although increasing evidence support the role of olfaction on dogs’ emotions and cognitive processes, very little research has been conducted on its relationship with memory in this species. The present study aimed at investigating the role of olfaction in the recall of detailed memories originally formed in the presence of a specific odor (i.e., vanilla). To test this, three groups of participants were trained with the same spatial learning task while a specific odor (i.e., vanilla) was dispersed in the testing room. Subjects were then divided in three experimental groups and after 24 h delay, they were presented with the same spatial task. The first group (Group 1) performed the task in the presence of a novel odor (i.e., control), whereas the second (Group 2) and the third group (Group 3) carried out the test in the presence of the vanilla odor and no odor (Group 3), respectively. After a brief delay, the test was presented again to the three groups of dogs: subjects of Group 1 were now tested in the presence of the vanilla odor, whereas the Group 2 was tested with the control odor. The Group 3 received no odor in both tests. A significant improvement of dogs’ performance was registered in the control-vanilla odors condition (Group 1), suggesting that the exposure to the odor presented at the encoding time would prompt the recall of spatial memories in dogs.

scholarly journals THE LATENT OF RHINOSINUSITIS AS A MANIFESTATION OF NEURO-IMMUNE INTERACTIONS

2019 ◽  
Vol 19 (1S) ◽  
pp. 111-112
Author(s):  
I V Stagniyeva ◽  
P A Stateshnaya
Keyword(s):  
Immune Deficiency ◽  
Inflammatory Cytokines ◽  
Pain Symptom ◽  
Cytokine Balance ◽  
Acute Bacterial Sinusitis ◽  
Group 3 ◽  
Group 2 ◽  
Th 1 ◽  
Group 1

Purpose: to determine the role of a pain symptom in the diagnosis of rhinosinusitis on the background of immune deficiency. 240 patients with rhinosinusitis without pain symptom were divided into 3 groups: group 1 - patients with acute viral rhinosinusitis (AVRS), group 2 - patients with acute bacterial sinusitis (ABRS), group 3 (n = 32) - control. All patients underwent a complete otorhinolaryngological examination, assessment of the pain symptom, an immunogram, the level of SP in the blood serum. At SP > 100 pg/ml in group 1, the change in indicators was typical for viral infection, in group 2, for bacterial infection. With an SP < 100 pg/ml, the cytokine balance is predominantly biased towards anti-inflammatory cytokines, and the direction of differentiation of Th-1/Th-2 lymphocytes towards the Th-2 pathway, which is manifested by immune deficiency, which leads to severe or prolonged course of the disease, which may indicate impaired neuro-immune interactions.

scholarly journals Role of Ajwa dates in ameliorating diclofenac sodium-induced nephrotoxicity and cardiovascular risk factors in mice

2019 ◽  
Vol 17 ◽  
pp. 205873921986157
Author(s):  
Heba M Eltahir ◽  
Naif Aljuhani ◽  
Sara A Alsubhi ◽  
Ghada M Alahmadi ◽  
Hossein M Elbadawy ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Diclofenac Sodium ◽  
Protective Effects ◽  
Group 3 ◽  
Group 2 ◽  
Endogenous Antioxidant ◽  
Per Oral ◽  
Altered Lipid ◽  
Group 1

The study aims at evaluating the protective effects of Ajwa dates extract against diclofenac sodium (DFS)-induced nephrotoxicity. A total of 30 male albino mice were divided into three groups. Group 1 received water per oral gavage for 14 days and saline per intra-peritoneal (IP) dose for the days 12–14. Group 2 received water like Group 1 and a daily IP dose of DFS for the days 12–14. Group 3 received 1 gm/kg Ajwa extract in water for 14 days and a daily IP dose for the days 12–14. Biochemical investigation revealed DFS-induced increase in serum urea and creatinine levels along with depleted antioxidant capacity, altered lipid profile, and hyperglycemia. Ajwa extract successfully protected against DFS-induced adverse effects, normalizing renal parameters biochemically and histologically, and prevented its hyperlipidemic and hyperglycemic effects. Ajwa protected against endogenous antioxidant capacity depletion in treated animals. Hydroalcoholic Ajwa extract is a promising candidate for protection against DFS-induced hyperlipidemia and nephrotoxicity.

Bacteriophages of Clostridium botulinum

1972 ◽  
Vol 18 (1) ◽  
pp. 67-76 ◽  
Author(s):  
C. E. Dolman ◽  
Eva Chang
Keyword(s):  
Clostridium Botulinum ◽  
Phage Type ◽  
Phage Group ◽  
Flexible Tail ◽  
Group 4 ◽  
Group 3 ◽  
Type C ◽  
Group 2 ◽  
Group 1

Temperate bacteriophages of diverse morphology were demonstrated by electron microscopy in toxigenic cultures of Clostridium botulinum. The 41 strains examined included 23 type E and multiple representatives of all other types. Cultures induced with mitomycin-C generally gave better yields, but phages were also demonstrable in untreated cultures.A provisional grouping of toxigenic types into four categories is suggested, based mainly upon associated phage patterns. Group 1 comprises types A, B, and F (all proteolytic), many of whose cultures showed an icosahedral contractile phage; others contained a "bullrushy" phage with elongated head and long flexible tail; some strains yielded both. Group 2, types B and F (non-proteolytic), were associated with icosahedral contractile phages; the latter also had an octahedral flexible phage. Group 3, types C and D, yielded conspicuously large phages with octahedral heads and very long sheathed tails. One type C strain produced a long-tailed icosahedral phage. Type E phages constituted group 4. These were icosahedral with tails generally contracted but sometimes flexible, often accompanied by superfluous sheathed tail-like structures resembling certain bacteriocins. Although non-toxigenic "OS" mutants of types A, B, E, and F were phageless, two non-toxic type E strains yielded phages. The possible role of lysogeny in the toxigenicity of certain types of this species is likely to prove difficult to elucidate.

scholarly journals Predictive Markers of Missed Miscarriage

2021 ◽  
Vol 11 (1) ◽  
pp. 65-67
Author(s):  
Agamurad Orazmuradov ◽  
Anastasiya Akhmatova ◽  
Khalid Haddad ◽  
Alexander Lopatin ◽  
Irina Bekbaeva ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Potential Role ◽  
Serological Markers ◽  
Liquid Chromatography Mass Spectrometry ◽  
Immunoglobulin Kappa ◽  
Serologic Marker ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The aim of this study was to find useful the serological markers for missed miscarriage (MM) in order to predict the outcome of pregnancy. The study included 141 pregnant women aged between 18 and 45 years at gestational age under 11 weeks. All women were divided into 3 groups. Group 1 included 68 women with MM; Group 2 included 43 women with spontaneous miscarriage; Group 3 included 30 pregnant women without pathology. Proteomic analysis of the blood serum was performed using liquid chromatography-mass spectrometry. The results of our study show that immunoglobulin kappa variable 3-15 (KV315) can be considered as the most promising serologic marker for MM in early gestation. The potential role of KV315 as the serological marker is very important for predicting the course of pregnancy.

scholarly journals Establishment of an orthodontic retention mouse model and the effect of anti-c-Fms antibody on orthodontic relapse

2019 ◽  
Author(s):  
Jiawei Qi ◽  
Hideki Kitaura ◽  
Wei-Ren Shen ◽  
Akiko Kishikawa ◽  
Saika Ogawa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteoclast Formation ◽  
Nickel Titanium ◽  
Clinical Issue ◽  
Retention Period ◽  
Group 3 ◽  
Group 2 ◽  
Group 1 ◽  
Orthodontic Retention

AbstractOrthodontic relapse after orthodontic treatment is a major clinical issue in the dental field. However, the biological mechanism of orthodontic relapse is still unclear. This study aimed to establish a mouse model of orthodontic retention to examine how retention affects the rate and the amount of orthodontic relapse. We also sought to examine the role of osteoclastogenesis in relapse using an antibody to block the activity of M-CSF, an essential factor of osteoclast formation. Mice were treated with a nickel-titanium closed-coil spring that was fixed between the upper incisors and the upper-left first molar to move the first molar in a mesial direction over 12 days. Mice were randomly divided into three groups: group 1, no retention (G1); group 2, retention for 2 weeks (G2); and group 3, retention for 4 weeks (G3). In G2 and G3, a light-cured resin was placed in the space between the first and second molars as a model of retention. Orthodontic relapse was assessed by measuring changes in the dimensions of the gap created between the first and second molars. To assess the activity and role of osteoclasts, mice in G3 were injected with anti-c-Fms antibody or PBS, and assessed for changes in relapse distance and rate. Overall, we found that a longer retention period was associated with a slower rate of relapse and a shorter overall amount of relapse. In addition, inhibiting osteoclast formation using the anti-c-Fms antibody also reduced orthodontic relapse. These results suggest that M-CSF and/or its receptor could be potential therapeutic targets in the prevention and treatment of orthodontic relapse.

scholarly journals Connective tissue dysplasia in the genesis of cervical incompetence

2021 ◽  
Vol 15 (1) ◽  
pp. 41-50
Author(s):  
E. V. Fotina ◽  
R. R. Zakirova ◽  
M. V. Alekseenkova ◽  
O. B. Panina
Keyword(s):  
Connective Tissue ◽  
Preterm Labor ◽  
Clinical Signs ◽  
Pregnancy And Childbirth ◽  
Cervical Incompetence ◽  
Connective Tissue Dysplasia ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Aim: to study a role of undifferentiated connective tissue dysplasia (uCTD) in etiology of cervical incompetence and its effect on pregnancy and childbirth course.Material and Methods. There were enrolled 60 patients with cervical incompetence. Patients were divided into 3 groups according to the modified CTD scale: group 1 - patients without uCTD (n = 21); group 2 - patients with mild uCTD (n = 25); group 3 - patients with moderate-to-severe uCTD (n = 14). Intensity of CTD clinical signs was assessed based on health status, gynecological and obstetric history, the course of pregnancy, labor and the postpartum period.Results. It was found that patients with more prominent CTD developed earlier (r-Spearman = -0.26) and more marked (r-Spearman = -0.29) cervical shortening and opening of the internal orifice of the uterus (r-Spearman = 0.28). It was also noted that likelihood of occurring preterm labor was significantly higher in patients with CTD (p = 0.02).Conclusion. The data obtained evidence that uCTD affects intensity of manifested cervical insufficiency and rate of preterm delivery.

Prognostic role of apolipoprotein and lactate dehydrogenase levels in resectable colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15541-e15541
Author(s):  
Yifei Ma ◽  
Ping Lu ◽  
Xinjun Liang ◽  
Shaozhong Wei
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lactate Dehydrogenase ◽  
Cox Regression ◽  
Prognostic Role ◽  
Free Survival ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

e15541 Background: Apolipoprotein b (apob), apolipoprotein a1 (apoa1), and lactate dehydrogenase (LDH) levels are circulating biomarkers that relate to tumor inflammation. This study aimed to evaluate the prognostic role of apob/apoa1 and LDH in resectable colorectal cancer (CRC). Methods: 513 patients of colorectal cancer (CRC) from Hubei cancer hospital were included finally, and we collected the pre-operative laboratory results within a week before surgery. We combined the two indicators and divided them into three groups (group 1: apob/apoa1-LDH low; group 2: apob/apoa1 or LDH high; group 3: apob/apoa1-LDH high). Kaplan-Meier survival analysis, univariate COX regression and multivariate COX regression were used to assess the prognoses of colorectal cancer patients. Results: The median follow-up was 35 months. Our study found that the prognosis of group 1 was better than group 2 in both overall survival (88.2% vs. 75.4% vs. 61.9%) (P≤0.001) and diseases-free survival (77.4% vs. 64.7% vs. 42.8%) (P≤0.001), and group 3 was the worst. By multivariate analysis, the new predictive marker obtained by combining apob/apoa1 and LDH could independently predict outcomes in CRC [overall survival: (HR: 1.487; 95% CI, 1.074-2.061); diseases-free survival (HR: 1.381; 95% CI, 1.045-1.827)]. Conclusions: New marker based on apob/apoa1 and LDH is useful for predicting the prognosis of patients with CRC. However, more research is needed in the future.

Prognostic significance of alterations of pathways regulating autophagy in acute myeloid leukemia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7038-7038 ◽  
Author(s):  
Giovanni Marconi ◽  
Maria Chiara Fontana ◽  
Cristina Papayannidis ◽  
Antonella Padella ◽  
Silvia Lo Monaco ◽  
...  
Keyword(s):  
Survival Data ◽  
Tp53 Mutation ◽  
Prognostic Significance ◽  
Snp Array ◽  
Physiological Role ◽  
Therapy Resistance ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

7038 Background: Nowadays, science is debating if autophagy in cancer can lead to therapy resistance or it can favor apoptosis. Autophagy pathways are involved pro-apoptotic mechanism, or they can improve stresses survival eliminating damaged mitochondria and proteins. Levels and activity of pro-apoptotic and anti-apoptotic proteins (eg. bcl-2 and p53), high levels of cAMP, and a pink/park complex could play as fulcrum on this lever. Our study aims to define the role of autophagy in AML. Methods: We analyzed 148 consecutive non M3 AML with Affymetrix SNP array. We screened all patients for TP53, FLT3, NMP1 mutations. Patients was treated with intensive induction chemotherapy regimens. Survival data were collected prospectively, with a median follow-up of 18 months. Results: Autophagy alteration (gene group 1: ULK1 CHR11; ULK1 CHR17; BECN1; ATG14; AMBRA1; UVRAG; ATG9A; ATG9B; PIK3C3; PIK3R4) was related to lower Complete Remission rate (CR%) after induction in univariate (p < .001) and multivariable regression model with age, karyotype, secondary AML, TP53 mutation (p = .014); autophagy alteration shown to confer worst Overal Survival (OS) (p < .001) and was significantly associated with complex karyotype and TP53 mutation (p < .001). We detected significant differences in term of survival independently both in gain and loss in group 1 genes (p < .001). Alterations in genes in cAMP pathway (group 2: SESN1; PRKAA1 CHR 3; PRKAB1: PRKAA1 CHR 1: PRKAG1 CHR11; PRKAG1 CHR 7; PRKAG3; PRKAB1) and in genes that could be related to a switch from a physiological role of autophagy to a resiliency mechanism (group 3: CCND1; BCL2; PINK1; PARK2; TP53; MDM1; MDM4) showed to confer worst OS (p < .001 in both groups); Alteration in group 2 and group 3 were related to lower CR% after induction (p < .001 in both groups). Whole Exome Sequencing on 56 patients in our set did not found any significant mutation in genes we analyzed with the exception of TP53. Conclusions: Alterations in autophagy regulator genes are associated with poor prognosis and therapy resistance. A loss in autophagy could block apoptosis, a gain could confer cell resiliency. Acknowledgements: ELN, AIL, AIRC, Progetto Regione-Università 2010-12,FP7 NGS-PTL, HARMONY

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