bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Characterization of Microglia-Associated Pro- and Anti-Inflammatory Genes in a Neonatal Inflammation-Sensitized Hypoxic-Ischemic Brain Injury Model
Authors: Bernis Maria E. , Schleehuber Yvonne , Zweyer Margit , Maes Elke , Felderhoff-Müser Ursula , Picard Daniel , Sabir Hemmen
Published: March 2022

Hypoxic-ischemic encephalopathy (HIE) mainly affects preterm and term newborns, leading to a high risk of brain damage. Coexisting infection/inflammation and birth asphyxia are key factors associated with intracerebral increase of proinflammatory cytokines linked to HIE. Microglia are key mediators of inflammation during perinatal brain injury, characterized by their phenotypic plasticity, which may facilitate their participation in both the progression and resolution of injury-induced inflammation. The purpose of this study was to investigate the temporal expression of genes associated with pro- and anti-inflammatory cytokines as well as the nucleotide-binding domain, leucine-rich repeat protein (NLRP-3) inflammasome from microglia cells. For this purpose, we used our established neonatal rat model of inflammation-sensitized hypoxic-ischemic (HI) brain injury in seven-day-old rats. We assessed gene expression profiles of 11 cytokines and for NLRP-3 using real-time PCR from sorted CD11b/c microglia of brain samples at different time points (3.5 h after LPS injection and 0, 5, 24, 48, and 72 hours post HI) following different treatments: vehicle, E. coli lipopolysaccharide (LPS), vehicle/HI, and LPS/HI. Our results showed that microglia are early key mediators of the inflammatory response and exacerbate the inflammatory response following HI, polarizing into a predominant proinflammatory M1 phenotype in the early hours post HI. The brains only exposed to HI showed a delay in the expression of proinflammatory cytokines. We also demonstrated that NLRP-3 plays a role in the inflammatory resolution with a high expression after HI insult. The combination of both, a preinfection/inflammation condition and hypoxia-ischemia, resulted in a higher proinflammatory cytokine storm, highlighting the significant contribution of acute inflammation sensitizing prior to a hypoxic insult on the severity of perinatal brain damage.
Development and Validation of an Ion-Pair HPLC-UV Method for the Quantitation of Quinoline and Indoloquinoline Alkaloids in Herbal and Pharmaceutical Antimalarial Formulations
Authors: Bekoe Samuel Oppong , Orman Emmanuel , Adjabui Samuel Awenteka , Brobbey Abena Amponsaa , Oppong-Kyekyeku James , Opuni Kwabena Frimpong-Manso , Kuntworbe Noble , Asare-Nkansah Samuel
Published: March 2022

Quinine- and cryptolepine-based antimalarials serve as valuable alternatives to artemisinin-based combination therapies (ACTs) in Ghana. Their use, however, is associated with adulteration and substandard quality challenges. An HPLC method targeting quinoline and indoloquinoline antimalarial alkaloids was developed, validated, and applied to evaluate herbal and pharmaceutical antimalarial formulations (HPAFs) and starting materials (APIs). The separation/quantitation of the alkaloids (including quinine, quinidine, cinchonine, cinchonidine, dihydroquinine, dihydroquinidine, and cryptolepine) was achieved on a Zorbax SB-CN column (250 mm × 4.6 mm, 5 μm), with an isocratic elution system of methanol: trifluoroacetic acid (0.1%, v/v) (15 : 85, v/v) at 1.5 mL/min and 223 nm. Method validation was according to ICH Q2(R1) guidelines. It was then used to assess the quality of APIs (n = 3) and HPAFs (n = 44) including quinine-based pharmaceutical antimalarial formulations (QBPAFs) (n = 23) and herbal antimalarial products (HAMPs). The method was found to be specific, selective, accurate, precise, and robust toward the alkaloids with linearity achieved within specified concentration ranges (r2 > 0.995 for all analytes). Analyte stability ranged between 6 and 12 hours. All the APIs contained quinine <99.0%–101.0%, with dihydroquinine and cinchonidine at levels compliant with the established acceptance criteria. The QBPAFs had quinine content ranging between 50.2% and 151.2%, with 43.5% (n = 10/23) of them complying with the acceptance criteria. The related alkaloids observed in the QBPAFs included quinidine (56.5%, n = 13/23), dihydroquinine (100%, n = 23/23), dihydroquinidine (21.7%, n = 5/23), cinchonine (17.4%, n = 4/23), and cinchonidine (95.7%, n = 22/23). For the HAMPs, 81.0% (n = 17/21) were adulterated with quinine (0.59 ± 0.04 mg/10 mL–86.03 ± 0.02 mg/10 mL). Cryptolepine was identified in 19% (n = 4/21) of the HAMPs with concentration ranging between 43.99 ± 0.43 μg/mL and 747.86 ± 0.34 μg/mL. In conclusion, the application of the ion-pair HPLC method targeting quinoline and indoloquinoline antimalarials has demonstrated the presence of quality and poor-quality HPAFs on the Ghanaian market.
Anti-Dlx5 Retards the Progression of Osteoarthritis through Inhibiting Chondrocyte Hypertrophy and Apoptosis
Authors: Lu Ye , Zhang Chengyuan , Jiang Shilin , Yuan Feng
Published: March 2022

Osteoarthritis is a common degenerative joint disease that can cause pain and disability in patients. There is still a lack of effective treatments to improve pathological changes of osteoarthritis cartilages and reverse the progression of osteoarthritis. Our study aimed to investigate the role of Dlx5 in papain-induced osteoarthritis. Osteoarthritis was induced through intraarticular injection of papain. The pathological damage of cartilage tissues was analyzed by H&E staining. The apoptosis of cartilage tissues was detected by TUNEL assay. Immunohistochemical staining was performed to detect DLX5 and BMP-2. Western blot was performed to detect the expressions of SP7, caspase-3, and MYC. The results showed that administration of anti-Dlx5 improved pathological changes of osteoarthritis cartilages, characterized by decreased chondrocyte proliferation, chondrocyte hypertrophy, and matrix damage. Anti-Dlx5 treatment decreased the expressions of BMP-2 and SP7, which are positive regulators of chondrocyte hypertrophy. Moreover, MYC and caspase-3, the critical mediators for chondrocyte apoptosis, were both decreased after anti-Dlx5 treatment. In conclusion, anti-Dlx5 retarded the progression of osteoarthritis by downregulating chondrocyte hypertrophy and chondrocyte apoptosis-related genes. Our findings suggests that Dlx5 is a promising target for osteoarthritis treatment.
Knowledge, Attitude, and Practice of Weaning among Mothers in Najran Region, Saudi Arabia, 2021
Authors: Al-Gashanin Musalli Ali , Ghazwani Eisa Yazeed
Published: March 2022

Background. Weaning is a complex process of a gradual introduction of complementary foods to the infant’s diet. It is recommended that solid food is introduced between 6 and 12 months of age. Weaning is difficult and potentially dangerous time for infants’ growth and mother’s education is an established determinant of its success. Little is known about weaning attitudes or practice among mothers in Najran Region of Saudi Arabia. Method. The study is a cross-sectional questionnaire-based observational investigation using random sampling scheme. We utilized ordinal logistic regression modelling to evaluate the relationship between demographic variables and knowledge level among mothers. Results. The total number included was n = 385 mothers who agreed to take part in the study. Good satisfactory knowledge rate was n = 135, 35.1%. Knowledge was mostly sought from other mothers (n = 102, 26.5%), followed by reliance on their own experience (n = 82, 21.3%). Seeking doctors’ advice was associated with better knowledge levels. Worse adjusted knowledge scores were associated with bottle feeding (OR = 0.5383,

p
=
0.0137

), using cerelac preparations (OR = 0.0316,

p
=
0.0092

), development of weaning symptoms (OR = 0.5869,

p
=
0.0260

), seeking other mothers’ advice (OR = 0.4750,

p
=
0.0226

), and feeding babies under 4 times daily (OR = 0.2742,

p
=
0.0008

). Mother education did not have significant impact on knowledge scores. Discussion. We confirmed, in this work, that knowledge levels were alarmingly unsatisfactory about weaning among our participants. Women were likely following local customs in terms of their choice of weaning methods even among the well-educated. The association between seeking doctors’ advice and better knowledge should be utilized in future educational interventions. Underfeeding babies of below 4 times daily was correlated substantially with poorer knowledge score. This could be viewed as reverse causality, as clearly more knowledgeable mothers are expected to stick to optimum feeding frequency. Recommendations. Communication channels between physicians and mothers need to be opened and widened through focused educational programmes. Poor knowledge is clearly associated with infant underfeeding and difficulties in recognizing weaning symptoms. Such points need to be emphasized in design of health education packages to nursing mothers. Research on knowledge about weaning should focus on its association with traditional weaning methods and bottle feeding.
Financial Geographical Structure and the Gap of Green Development: Evidence from Chinese Cities
Authors: Zhao Jianhua
Published: March 2022

In the context of common prosperity, it is of great significance to explore the influence and mechanism of financial development on the gap of green development. This study takes 250 prefecture‐level cities in China from 2003 to 2019 as the research object and empirically tests the influence of financial development on the gap of green development by using the super‐efficiency SBM model, the two‐way fixed effect model, and the mediating effect model. It is found that local financial effect can significantly narrow the gap of green development, while financial spillover effect of the central city can widen the gap of green development. The mechanism analysis shows that enhancing the advancement of human capital helps to optimize the utilization efficiency of financial resources outside the city and thus narrows the gap of green development. Local financial effect narrows the gap by the optimization of industrial structure, the improvement technological innovation, and the decrease of resource dependence, while financial spillover effect narrows the gap only by the optimization of industrial structure. The heterogeneity analysis demonstrates that local financial effect significantly narrows the gap of green development in cities that are 100–200 KM away from the central city in the central region, while financial spillover effect significantly enlarges the gap of green development in cities that are 100–300 KM away from the central city in the western region. The research in this paper facilitates the understanding of the influence of financial development on the gap of green development and puts forward relevant policy suggestions.
Investigating Large-Scale Network with Unified Granger Causality Analysis
Authors: Hu Zhenghui , Li Fei , Cheng Minjia , Lin Qiang
Published: March 2022

As the concept of integrating global neuron coupling effect is increasingly accepted, investigating causal connection increasingly requires the intervention of large-scale analysis. In this study, a large-scale brain network analysis was carried out by a description length guided framework, which involves a unified Granger causality analysis (uGCA) method and now integrates the concept of large-scale analysis. This will be helpful to make a more comprehensive determination for causal connection among the global brain regions. Distinct from the conventional GCA, which involves a two-stage scheme consisting of Akaike information criterion or Bayesian information criterion (AIC/BIC) and

F

-test to obtain a causal effect, a unified guided framework can ensure more reliable results while eliminating some confounding influences among network nodes. Then, we performed large-scale network simulation experiments involving 13 nodes; it was found that our proposal was more accurate and robust in guiding the causal connection investigation of large-scale networks. When it comes to the resting-state fMRI datasets, we studied a 90-node network selected from the Anatomical Automatic Labeling (AAL) template. Then, combining a K-means clustering method, we found that most brain nodes in the connection network obtained by uGCA methods were gathered into the corresponding functional brain regions and functionally related regions cooperated with each other. Compared to conventional GCA, their results were more consistent with clinical and anatomical priors. Moreover, in studies of several large-scale functional networks involving default mode network (DMN), dorsal attention network (DAN), and frontoparietal control network (FCN), the uGCA method more clearly revealed their empirical cooperation. As a brain with numerous nodes and massive connections, a unified large-scale analysis method is of great significance for the integration of causal connections in the whole brain network in the future.
Low Molecular Weight Fucoidan Inhibits Pulmonary Fibrosis In Vivo and In Vitro via Antioxidant Activity
Authors: Dong Huidan , Xue Tao , Liu Yanjuan , He Shan , Yi Yanliang , Zhang Bo , Xin Jie , Wang Zhen , Li Xinpeng
Published: March 2022

In this study, sulfated polysaccharides extracted from Laminaria japonica were degraded by free radicals to obtain low molecular weight fucoidan (LMWF). The in vivo and in vitro effects of LMWF on bleomycin-treated pulmonary fibrosis mice and TGF-treated A549 cells, respectively, were evaluated, and the role of antioxidant activity was assessed. H&E, Masson’s trichrome, and Sirius red staining results showed that bleomycin induced obvious pathological changes and collagen deposition in the lung tissue of mice. However, LMWF effectively inhibited collagen deposition, and based on immunohistochemistry analyses, LMWF can also inhibit the expression of fibrosis markers. At the same time, LMWF could regulate related antioxidant factors in the lung tissue of pulmonary fibrosis mice and reduce the pressure of oxidative stress. Moreover, LMWF could improve the morphology of cells induced with TGF, which confirmed that LMWF could inhibit fibrosis via antioxidant activity modulation.
Synthesis and Applications of Green Synthesized TiO2 Nanoparticles for Photocatalytic Dye Degradation and Antibacterial Activity
Authors: Shimi Annin K. , Ahmed Hiwa M. , Wahab Muhammad , Katheria Snehlata , Wabaidur Saikh Mohammad , Eldesoky Gaber E. , Islam Md Ataul , Rane Kantilal Pitamber
Published: March 2022

Metal oxide photocatalyst is one of the promising photocatalysts in the water remediation process. The present work is aimed at synthesizing the green production of TiO2 (G‐TiO2) nanoparticles from mulberry plant extract. Plant phytochemicals serve a different role to produce the nanophase particles. The bioreductant is safer and noxious free compound for synthesizing the G‐TiO2 nanoparticles. The synthesized G‐TiO2 nanoparticles in anatase phase and their crystallite size of 24 nm were characterized from X‐ray diffraction analysis. The Ti‐O bonding and plant derivatives and their reduction were confined from FTIR analysis. The wide bandgap of G‐TiO2 nanoparticles (3.16 eV) and their optical characterization were captured from UV‐DRS analysis. The spherical surface morphology and their Ti and O elemental configurations were characterized from FESEM with EDX technique. The photocatalytic dye degradation was examined against methylene blue dye, and their pseudo‐first‐order kinetics were evaluated. The cyclic experiments declared their catalytic potential. The bacterial resistance of G‐TiO2 nanoparticles was examined against gram‐positive and gram‐negative bacteria. Hence, the catalytic potential and bacterial stability of G‐TiO2 nanoparticles are the powerful candidate for water remediation and biomedical applications.
Telehealth-Delivered Cognitive Behavioral Therapy for Insomnia in Individuals with Multiple Sclerosis: A Pilot Study
Authors: Turkowitch David , Ludwig Rebecca , Nelson Eryen , Drerup Michelle , Siengsukon Catherine F.
Published: March 2022

Background. Over 50% of individuals with multiple sclerosis (MS) have moderate or severe sleep disturbances, insomnia being the most common. In-person cognitive behavioral therapy for insomnia (F2F-CBTi) is currently the first-line treatment for insomnia. However, given potential limitations to access including mobility difficulty, fatigue, or living in a rural area, telehealth-delivered CBT-I (tele-CBTi) has been considered as an alternative treatment. The purpose of this study was to assess the feasibility and treatment effect of tele-CBTi in people with MS and compare it to outcomes from a F2F-CBTi study in individuals with MS. Methods. 11 individuals with MS and symptoms of insomnia participated in 6 weekly CBT-I sessions with a trained CBT-I provider via live video. Insomnia severity (ISI), sleep quality (PSQI), and fatigue severity (FSS and MFIS) were assessed pre- and posttreatment as primary outcomes. Sleep onset latency (SOL), sleep efficiency (SE) and total sleep time (TST) from the PSQI, depression (PHQ-9), anxiety (GAD-7), sleep self-efficacy (SSES), and quality of life (MSIS-29) were also assessed pre- and posttreatment as secondary outcomes. Results. Participants resided in 9 different states. Retention and adherence rates were 100%. There were significant improvements in ISI, PSQI, MFIS, FSS, SOL, SSES, PHQ-9, and MSIS-29, but not SE, TST, or GAD-7. There were no significant differences between the F2F-CBTi group and tele-CBTi group for magnitude of change in the primary outcomes (ISI, PSQI, MFIS, and FSS) or the secondary outcomes (SOL, SE, TST, SSES, PHQ-9, GAD-7, and MSIS-29). Conclusions. Tele-CBTi is feasible and has outcome measures that are similar to that of in-person CBT-I treatment. Tele-CBTi may increase access to insomnia treatment in individuals with MS.
Fejér–Pachpatte–Mercer-Type Inequalities for Harmonically Convex Functions Involving Exponential Function in Kernel
Authors: Butt Saad Ihsan , Yousaf Saba , Khan Khuram Ali , Matendo Mabela Rostin , Alsharif Abdullah M.
Published: March 2022

In the present study, fractional variants of Hermite–Hadamard, Hermite–Hadamard–Fejér, and Pachpatte inequalities are studied by employing Mercer concept. Firstly, new Hermite–Hadamard–Mercer-type inequalities are presented for harmonically convex functions involving fractional integral operators with exponential kernel. Then, weighted Hadamard–Fejér–Mercer-type inequalities involving exponential function as kernel are proved. Finally, Pachpatte–Mercer-type inequalities for products of harmonically convex functions via fractional integral operators with exponential kernel are constructed.
Identifying Key Influential Factors of Bid Evaluation in Government Public Project Green Procurement in China Using BP-DEMATEL Model
Authors: Zhang Yi , Chen Qiang
Published: March 2022

With the global resource and environment problems becoming increasingly prominent and the government procurement scale growing rapidly, the implementation of green procurement for government public project will have a significant impact on the protection of resources and environment. Identifying the key influential factors of bid evaluation in government public project green procurement is of great significance for promoting the construction of government public project green procurement system. Based on the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method, Back Propagation (BP) neural network is introduced to determine the direct-relation matrix, optimizing the traditional DEMATEL method. This paper uses the BP-DEMATEL model to identify key influential factors of bid evaluation in government public project green procurement by algorithmic design. Among 56 indicators, which have formed a set of index system of bid evaluation in government public project green procurement, 20 key influential factors are identified, providing reference for the government to implement green procurement in the field of public project. The research results not only enrich and improve the theoretical and practical research in the field of government public project green procurement, but also solve the defects of traditional DEMATEL method that the method is too subjective and tedious when obtaining the influence degree between each pair of factors to construct direct-relation matrix through questionnaire surveys or expert scoring method, thus expanding the scope of the application of the DEMATEL method.
On Robust Stability for Hurwitz Polynomials via Recurrence Relations and Linear Combinations of Orthogonal Polynomials
Authors: Arceo Alejandro , Flores Héctor F. , Garza Lino G. , Garza Luis E. , Romero Gerardo
Published: March 2022

In this contribution, we use the connection between stable polynomials and orthogonal polynomials on the real line to construct sequences of Hurwitz polynomials that are robustly stable in terms of several uncertain parameters. These sequences are constructed by using properties of orthogonal polynomials, such as the well‐known three‐term recurrence relation, as well as by considering linear combinations of two orthogonal polynomials with consecutive degree. Some examples are presented.
Effects of IncRNA PROX1-AS1 on Proliferation, Migration, Invasion and Apoptosis of Lung Cancer Cells by Regulating MiR-1305
Authors: Zhao Quanneng , Zhang Bing , Li Zhilian , Tang Wei , Du Lijun , Sang Hongyang
Published: March 2022

This paper aims to explore the lncRNA PROX1-AS1 effect on proliferation, migration, invasion, and apoptosis of lung cancer cells together with its targeted regulation on miR-1305. To adopt qRT-PCR to test PROX1-AS1 and miR-1305 expression levels in lung cancer tissues and adjacent tissues. Lung cancer cells A549 were cultured in vitro and randomly divided into several groups, which are si-NC, si-PROX1-AS1, miR-NC, miR-1305, si-PROX1-AS1 plus anti-miR-NC, and si-PROX1-AS1 plus anti-miR-1305. To adopt the CCK-8 method to test cell proliferation and to adopt the Transwell chamber experiment to test cell migration and invasion. To adopt the flow cytometry method to test the apoptosis rate. Through a dual luciferase experiment, we decided to find out the targeting relationship between PROX1-AS1 and miR-1305. Then we adopted the western blot method to test CyclinD1, MMP-2, MMP-9, Bcl-2, p21, and Bax expression levels. Compared with adjacent tissues (

P
<
0.05

), the expression of PROX1-AS1 in lung cancer tissue was remarkably higher, while the expression of miR-1305 was remarkably lower (

P
<
0.05

). After PROX1-AS1 knockdown expression or miR-1305 overexpression, cell activity, migration, and invasion ability were outstandingly lowered (

P
<
0.05

), but the apoptosis rate was obviously raised (

P
<
0.05

), CyclinD1, MMP-2, Bcl-2, and MMP-9 protein data were remarkably reduced (

P
<
0.05

), but p21 and Bax protein conditions were outstandingly enhanced (

P
<
0.05

). The dual luciferase experiment confirmed that PROX1-AS1 had a targeting relationship with miR-1305. After cotransfection with si-PROX1-AS1 and anti-miR-1305, the cell viability, migration and invasion ability were remarkably enhanced (

P
<
0.05

), the apoptosis rate was remarkably reduced (

P
<
0.05

), CyclinD1, MMP-2, Bcl-2, and MMP-9 protein were increased remarkably (

P
<
0.05

), and p21 or Bax protein was lowered remarkably (

P
<
0.05

). On the one hand, PROX1-AS1 can promote lung cancer proliferation, migration, and invasion. On the other hand, it may restrain apoptosis, possibly through inhibiting miR-1305 expression.
Recherches sur l’activité des enzymes dans le métabolisme des mucopolysaccharides des veines saphènes humaines saines ou variqueuses
Authors: Niebes P. , Laszt L.
Published: March 2022

In the intact and varicose saphenous vein of man, we have studied some lysosomal enzymes which interfere in the metabolism of mucopolysaccharides. The activity of all the enzymes studied except cathepsine is significantly enhanced in the varicose vein. The signification of these results is discussed with respectto the structure of the connective tissue.
Untersuchungen über die Hämodynamik des Karotiskreislaufes mit Hilfe von Impedanzmessungen
Authors: Hardung V. , Laszt L.
Published: March 2022

The main purpose of the present work was to study the influence of muscular activity on the dynamic behavior of the carotid artery. To this purpose we determined the input impedance of the vessel as a function of frequency. On the other hand, we calculated such impedances theoretically for an elastic tube model closed at the peripheral end, using different parameters such as speed of propagation, damping constant and length. Even a mere qualitative comparison of the experimentally obtained with the calculated impedance-curves yields the following interesting results: if we cancel the muscular activity by injection of papaverine, the carotid clamped at the peripheral end shows a picture which closely ressembles the theoretical one. Also a natural clamped carotid, not influenced by any drug, still shows some general features of the theoretical picture. On the other hand, a striking difference can be observed under the influence of the pressure reducing polypeptide firstly obtained by Laszt [6]. In this case, phase shifts between pressure and flow are largely enhanced beyond the theoretically calculated limits from –90° to +90°. These large phase-shifts can only be accounted for by a negative damping constant β. This, in turn, means that we must introduce in the theory some kind of an amplifying element due to muscular activity. A further interesting result can be obtained if we record pressure and flow shortly after the removal of the clamp. In this case, the impedance-curves show the behavior of a tube with an open end not encountered normally in the arterial circulation. This might be attributed to reactive hyperemia of the peripheral vessels.
Zur therapeutischen Beeinflussung des akuten experimentellen lymphostatischen Ödems mit Vitaminen, vitaminartigen Naturstoffen sowie mittels Massage
Authors: Börcsök Ethel , Földi Katharina , Wittlinger G. , Földi M.
Published: March 2022

(1) A plethysmographic method has been deviced which measures oedema of the muzzle and neck with high accuracy. (2) Acute lymphostatic oedema of the muzzle and neck was induced by ligation of the cervical lymph glands. (3) By the treatment with various vitamins and vitamin-like substances on the one hand and by massage on the other a statistically significant protection can be achieved against acute lymphostatic oedema.
Ergotamine Gangrene in Various Inflammatory Conditions
Authors: Görög P. , Kovács Iren B.
Published: March 2022

Given in subtoxic doses to the rat, ergotamine produced tail gangrene in not more than 20% of animals. The incidence rate of ergotamine gangrene was not influenced by acute Mammation (carrageenin, dextran oedema). However, when inflammation was produced by immersing the tail of the rat in dimethyl sulfoxide, the incidence rate of ergotamine gangrene was greatly increased. The gangrene-inducing effect of ergotamine was significantly increased in rats with adjuvant arthritis or 6-sulphanylamido-indazole arthritis. Like arthritic rats, rats with lathyrism due to chronic treatment with aminoacetonitrile were also more sensitive to the gangrene-inducing effect of ergotamine. Ergotamine-induced tail gangrene in adjuvant arthritic rats is a good model for use in research for drugs which are effective against the vascular complications of ‘collagen’ diseases.
14C and 35S-SO4 Metabolism of Acid Glycosaminoglycans in Bovine Heart Valves
Authors: Figura K.v. , Born W. , Buddecke E.
Published: March 2022

Bovine heart valves metabolize up to 96% of exogenous 14C-glucose to lactate when incubated in vitro under appropriate conditions. Small proportions of the 14C-radioactivity are incorporated into glycogen, glycosaminoglycans and lipids and are oxydized to 14CO2. Difference between the valves of the left ventricle (aortic and mitral valve) and of the right ventricle (pulmonary and tricuspid valve) were found in the rate of glycolysis as well as in the collagen, glycogen and glycosaminoglycan content. The in vitro incorporation of [U-14C] glucose radioactivity into the total glycosaminoglycans resulted in a specific labelling of hyaluronic acid, dermatan sulfate and chondroitin sulfate, but the specific radioactivities of the individual glycosaminoglycans and their relative rates of biosynthesis differed markedly. The relative rates of biosynthesis were 2.9–7.6 for hyaluronate, 1.0 for dermatan sulfate and 0.26–0.59 for chondroitin sulfate. After labelling the sulfated glycosaminoglycans with 35S-sulfate, the metabolic heterogeneity of dermatan sulfate and chondroitin sulfate was confirmed, but, in addition, heparan sulfate – not previously detected in heart valves – was identified as a third sulfated glycosaminoglycan. Chemical analyses of heparan sulfate revealed a sulfate/uronic ratio of 0.5; its relative amount was found to be 2–4% of the total glycosaminoglycans. Analogous chemical and metabolic data were obtained with chordae tendineae, except that a higher relative percentage of dermatan sulfate was found than in the corresponding heart valves.
Increase in Bronchial Resistance during Infusion of Thrombin into the Venous Circulation of Guinea Pigs
Authors: Görög P. , Kovacs Iren B.
Published: March 2022

Bronchial resistance was measured by the lung overflow technique in guinea pigs. Intravenous infusion of thrombin produced a significant increase of bronchial resistance, induced by platelet constituents released from the thrombi and deposited in the arteries and capillaries of the lung. This was evidenced by increase of bronchial resistance and mortality having been aggravated by e-aminocaproic acid (inhibition of fibrinolysis), by infusion of gelatin (sludge phenomenon) as well as by catecholamines (stress effect) and significantly inhibited by massive doses of heparin and by experimental thrombocytopenia. Emphasis is laid on the significance of pulmonary microembolism in the development of severe pulmonary hypertension and edema, the cause of which is difficult to diagnose clinically, yet demonstrable at autopsy. The recommended method is held to be suitable for the objective study of the process in animal experiment.
Pulmonary Vascular Reactivity in the Spontaneously Hypertensive Rat
Authors: McMurtry I.F. , Petrun M.D. , Tucker A. , Reeves J.T.
Published: March 2022

We examined the pulmonary vascular reactivity of normotensive rats (NR) and spontaneously hypertensive rats (SHR) to acute and chronic pressor stimuli. In rats kept at low altitude (1,520 m), SHRhad a slight degree of right ventricular hypertrophy, but there was no difference between SHRand NR in either right ventricular systolic pressure or pulmonary artery wall thickness. When compared to blood-perfused lungs from low altitude NR, lungs from low altitude SHR were normoresponsive to acute airway hypoxia, hyporesponsive to intra-arterial angiotensin II, and hyperresponsive to intra-arterial prostaglandin F2α. After exposing rats to simulated high altitude (4-6 weeks at 4,270 m) to induce hypoxic pulmonary hypertension, SHRhad a higher right ventricular systolic pressure, a greater degree of right ventricular hypertrophy, and more pulmonary artery medial thickening than did NR. The results indicate that although the pulmonary vasculature of SHRdoes not become hypertensive spontaneously, it might have an increased tendency to develop hypertension when exposed to an appropriate stimulus, i.e., chronic airway hypoxia.
Responses of Small Rabbit Pial Arteries in vitro
Authors: Duckles Sue Piper , Bevan John A.
Published: March 2022

An in vitro method for measuring changes in isometric force of vessels as small as 100 µm in outer diameter was used to determine whether the adrenergic mechanism of small pial arteries is the same as the large arteries of the circle of Willis. Fluorescence histology demonstrated the rich noradrenergic innervation of small branches of the middle cerebral artery. In spite of this rich innervation, contractile responses to transmural stimulation (TNS) were much smaller than maximum responses to histamine. An insensitivity to exogenous norepinephrine was shown which could account for this small response to TNS. In the presence of low concentrations of histamine, responses to TNS were increased. Thus, small pial arteries have characteristics similar to larger cerebral arteries.
Frequency-Dependent Control of Nutritional and Nonnutritional Circuits in the Dog Paw
Authors: Baker Carleton H. , Davis Darrell L. , Sutton E.T.
Published: March 2022

The neural control of blood flow and volume distribution between parallel nutritional and nonnutritional circuits has been investigated in 13 vascularly and neurally isolated dog hindpaws. The superficial and deep fibular nerves and the tibial nerve were cut and individually stimulated at frequencies of 0.1, 1, 5, 10 and 15 Hz. Increasing stimulation rates to each nerve progressively increased blood flow resistance. Vascular volume changes were determined by indicator dilution and tissue volume changes by plethysmography. The permeability surface area product of 86Rb (PS) and the capillary filtration coefficient (CFC) were determined. Superficial fibular nerve and deep fibular nerve stimulations caused progressively increased nonnutritional circuit constriction with increasing stimulation frequencies resulting in blood flow redistribution to the nutritional circuit as evidenced by increasing PS and CFC values. Tibial nerve stimulation at 0.1 Hz caused nonnutritional circuit constriction and blood flow redistribution to the nutritional circuit (PS and CFC increased). As the stimulation frequency was increased, there was progressive increase of the nutritional circuit constriction and altered blood flow distribution; i.e., CFC and PS decreased with increasing frequency of stimulation, presumably due to predominantly arterial segment resistance increase.
Changes in Rat Aortic Actomyosin Content with Maturation
Authors: Seidel C.L. , Murphy R.A.
Published: March 2022

It has been reported by several investigators that the maximum active force generating ability (i.e., force/tissue cross-sectional area) of the aorta increases as the animal matures and then declines later in life. The purpose of this work was to determine if changes in the actomyosin content of the aorta occur during maturation which could contribute to the observed changes in force generating ability. The actin and myosin contents of rat thoracic aorta obtained from animals 3, 5, 7, 16 and 43 weeks of age were determined by quantitative gel electrophoresis, and were normalized with respect to tissue mass and protein and DNA contents. The results indicate that the amount of actomyosin (i.e., actin + myosin heavy chains) per tissue mass, protein and DNA increases rapidly during the first 5 weeks after birth and then remains constant. These observations suggest that the increasing actin and myosin heavy chain content of aorta observed early in life could explain in part the increasing force generating ability reported during this period, but that a loss of contractile material is not responsible for the reduction in force generating ability seen later in life.
Demonstration of a Putative Adenosine Receptor in Rabbit Aorta
Authors: Ghai Geetha , Mustafa Jamal
Published: March 2022

This study demonstrates the existence of adenosine receptor(s) in a homogeneous population of cultured smooth muscle cells and intact muscle strips from rabbit aorta. Binding assays with 3H-adenosine were performed using the crude microsomal fraction of the cultured cells. Adenosine binding was reversible and displayed a single species of saturable binding sites. The nuclear and soluble fractions showed negligible binding. Adenosine uptake blockers (e.g., nitrobenzylthioinosine, dipyridamole) had no effect on its binding. Theophylline inhibited the binding and the relaxation of aortic strips to adenosine. The data suggest the existence of specific binding sites for adenosine on the surface of aortic smooth muscle cells.
Effect of Thrombin on Isolated Canine Blood Vessels
Authors: Janssens W.J. , Verhaeghe R.H.
Published: March 2022

The aim of the present study was to assess whether or not thrombin affects vascular smooth muscle activity by a direct action on the blood vessel wall. In isolated saphenous veins and femoral and pulmonary arteries thrombin did not affect basal tension, but in pulmonary and portal mesenteric veins it caused contraction. In saphenous and femoral veins and in femoral and pulmonary arteries the enzyme depressed contractions evoked by α-adrenergic stimulation. In the saphenous vein thrombin also depressed contractions induced with acetylcholine or potassium ions. In this blood vessel the relaxation caused by thrombin was abolished by antithrombin III and the tripeptide D-phenylalanine-proline-arginine-CH2Cl, a specific inhibitor of the enzymatic center of thrombin. In pulmonary and portal mesenteric veins, thrombin potentiated the contractile response to norepinephrine. These contractile effects of thrombin were also abolished by D-phenylalanine-proline-arginine-CH2Cl. Thus, thrombin causes relaxation or contraction of blood vessels through a direct action on the blood vessel wall. These effects are due to its proteolytic activity.
Inhibition by Methoxyverapamil of the Responses of Smooth Muscle from Spontaneously Hypertensive and Normotensive Rats
Authors: Nghiem C. , Swamy V.C. , Triggle D.J.
Published: March 2022

Inhibition by methoxyverapamil (D 600) of the responses to norepinephrine (NE) and KCl of vascular (carotid and iliac arteries and aortae) strips and vasa deferentia from spontaneously hypertensive (SHR) and normotensive rats (WKY) were compared. The responses of aortic and carotid arterial strips from SHR to NE and KCl were inhibited to a lesser extent by low concentrations of D 600 (≤10–6M). The isolated preparations of the iliac arteries and the vasa deferentia showed no differences in their susceptibility to inhibition by D 600. The responses to NE and KCl in calcium-free solutions of vascular strips from WKY were generally resistant to inhibition by D 600 (10–6M) in contrast to those from SHR which were markedly inhibited by D 600. Our results demonstrate that while the inhibitory action of D 600 on calcium movement may succeed in distinguishing vascular responses of SHR from those of WKY, the inhibitory pattern varies with different tissues and with experimental variations of calcium levels.
Length-Tension Properties of the Anterior Tibial Artery in Normotensive and Perinephritic Hypertensive Dogs
Authors: Price Joel M. , Davis D.L. , Baker C.H.
Published: March 2022

The length-active tension relation has been previously reported to be decreased or unchanged in hypertensive vessels whereas resting distensibility was unchanged or increased. We found the maximum active stress and the internal ring circumference, in millimeters, at which it occurs (Lmax) to be lower in arterial rings from perinephritic hypertensive dogs than in rings from normotensive dogs. The internal circumferences (length) at which resting force and active force became zero (L₀ and Lmin, respectively) were unchanged. Lmax, L₀ and Lmin were used to normalize length-tension diagrams. Active stress was significantly lower in hypertensive vessels at most of the lengths tested with the diagram normalized to Lmax· When the length-tension diagram was normalized to Lmin there was no difference in the active stress at any of the lengths tested. The length-resting stress curves were identical when the diagram was normalized to Lmax but the curve for hypertensive vessels was higher when the diagram was normalized to L₀. An important characteristic of these length-tension curves is that normalized lengths correspond to the same absolute length in each group of vessels when the reference length has the same absolute value (L₀ and Lmin in this study). This separates differences due to absolute length from differences associated with hypertension. We conclude that perinephritic hypertension in the dog is accompanied by a decrease in resting distensibility of the arterial wall. The results indicate that the choice of reference length may affect the values of stress and tension that are obtained for comparison of length-tension relationships in hypertensive and normotensive blood vessels.
Angiotensin Tachyphylaxis in the Isolated Rabbit Aorta
Authors: Oshiro Maria E.M. , Miasiro Nobuco , Paiva Therezinha B. , Paiva Antonio C.M.
Published: March 2022

The effect of modifications of the N-terminal end of the angiotensin II (AII) molecule on its ability to induce tachyphylaxis in the isolated rabbit aorta was studied by analyzing the effects of several analogs of AIL No tachyphylaxis to AII was observed, but (1-sarcosine)-AII, (1-guanido-acetic)-AII and (1-glycine)-AII induced marked tachyphylaxis. (1-Betaine)-AII, (2-lysine)-AII, (2-ornithine)-AII and (1-sarcosine,2-lysine)-AII were unable to induce tachyphylaxis in the rabbit aorta. A positively charged N terminus and the guanidino group of the Arg2 side chain appear to be needed for the manifestation of the tachyphylactic property, while the Asp1 side chain is responsible for the absence of tachyphylaxis to AII. It is proposed that the analogs that are able to induce tachyphylaxis, after binding to the receptor to produce the agonistic response, induce a slow conversion of the hormone-receptor complex into a tachyphylactic state, and that this conversion is promoted by the interaction of the N terminus and the guanidino group of the analog with their complementary sites.
Comparison of Fenestrations in Internal Elastic Laminae of Canine Thoracic and Abdominal Aortas
Authors: Song S.H. , Roach Margot R.
Published: March 2022

All nonelastin tissue was removed from canine aortas by placing them in 0.1 N NaOH at 75 °C for varying periods of time. The segments of aorta were weighed in a Mettler Chemical Balance at intervals. In 10 dogs the average weight of the thoracic aorta was 5.01 ± 0.388 (SE) g while that of the abdominal aorta was 3.08 ± 0.346 g. After digestion, the thoracic aorta weighed 3.34 ± 0.0275 g and the abdominal aorta 0.85 ± 0.085 g. Thus, the elastin makes up 67% of the thoracic aorta but only 28% of the abdominal aorta. These are equivalent to 0.334 g/kg body weight for the thoracic aorta and 0.224 g/kg body weight for the abdominal aorta. The values were always stable between 5 and 7 h and usually between 3 and 12 h. Aortic elastin was obtained from 5 dogs after 5-7 h of digestion and prepared for analysis by scanning electron microscopy. The dimensions of the fenestrations in the internal elastic laminae were quantified as described previously. The lower abdominal aorta had the largest holes (2.227 ± 0.048 µm), and the upper thoracic aorta the smallest holes (0.954 ± 0.032 µm). There was no significant difference in the size of the fenestrations along the thoracic aorta, but those in the lower abdominal aorta were larger than those in the upper abdominal aorta. The possible significance of the fenestrations in the genesis of aortic disease is discussed briefly.
Absence of a Role for Superoxide Anion, Hydrogen Peroxide and Hydroxyl Radical in Endothelium-Mediated Relaxation of Rabbit Aorta
Authors: Silin Paulie J. , Strulowitz Judith A. , Wolin Michael S. , Belloni Francis L.
Published: March 2022

We tested the hypothesis that the endothelium-dependent relaxation of rabbit thoracic aorta in vitro is mediated by reduced metabolites of oxygen. Helical vascular strips were contracted with either norepinephrine or phenylephrine. Oxygen metabolites, generated by the xanthine oxidase reaction, completely relaxed norepinephrine-induced contractile tone but not tone induced by phenylephrine. A mixture of oxygen metabolite scavengers (superoxide dismutase, catalase and mannitol) eliminated the relaxation induced by the xanthine oxidase products. Acetylcholine caused a dose-dependent and endothelium-dependent relaxation of the strips; this was not inhibited by the presence of the scavengers. We conclude that reduced oxygen metabolites have little direct effect on rabbit aortic smooth muscle in vitro, although they indirectly but specifically relax norepinephrine-induced tone, presumably by oxidation of norepinephrine. Oxygen metabolites do not appear to mediate the endothelium-dependent relaxation response of this tissue to acetylcholine.
Lactate Transport in Rat Aorta
Authors: Kutchai Howard , Geddis Lisa M.
Published: March 2022

1. Ouabain (10 mM) and gramicidin (5 µg/ml) do not inhibit lactate uptake by rat aortic rings. This supports the integretation that a Na+ gradient is not involved in lactate transport. 2. Dinitrophenol (25 µM) fails to inhibit lactate uptake, suggesting that oxidative metabolism is not required for lactate uptake. 3. DIDS (4,4’-diisothiocyano-2,2’-stilbenedisulfonate), quercetin, and α-cyano-4-hydroxycinnamate – agents that have been reported to inhibit lactate transport in other cell types -were ineffective in inhibiting lactate transport in rat aortic rings.4. Inhibition of lactate uptake by glyceraldehyde is not stereospecific, does not involve inhibition of glucose phosphorylation, and does not appear to involve interaction with membrane sulfhydryls. PCMBS (p-chloromercuribenzenesulfonate) does not markedly inhibit the initial rate of lactate uptake, but diminishes the lactate space at later times.5. Pyruvate, phenylpyruvate, and thiolactate inhibit lactate uptake, but propionate and glycolate are poor inhibitors.
Scanning Electron Microscopy of Elastic Networks from the Bifurcation Region of Guinea Pig Carotid Arteries
Authors: Shin H.S. , Hulbert W.C. , Biggs D.F.
Published: March 2022

We isolated the elastic network from the bifurcation region of guinea pig carotid arteries by treatment with hot alkali and examined its adventitial and adluminal components by SEM. The thickness of networks from common and external carotid arteries averaged 87.5 µm (±6.9 SD) and from the carotid sinus averaged 46.8 µm (±2.4 SD). The networks consisted of a mesh of elastic tissue that became a continuous sheet, 2 µm thick, which formed the internal elastic lamina (IEL). The IEL was fenestrated; the perforations varied in number among the vessels (occipital > carotid sinus > common = external carotid), and some were spanned by delicate elastic fibers. The IEL’s adluminal surface was a smooth membranous sheet, which in some specimens bore unidirectional loose fibers, or was composed of tightly fused bundles of uni- or multidirectional fibers. The interior region of the cranial carotid sinus contained unique blister-like structures and dense clusters of fenestrations, together with a honeycomb-like mesh near the ascending pharyngeal artery. The outer, adventitial elastic layer consisted of a network of loose elastic fibers that were fused with the inner layers. We conclude that the structural differences noted among the common and external carotid arteries and carotid sinus are related to the sinus’s unique pressure-sensing functions.