Endothelin effects in isolated, perfused lamb lungs: role of cyclooxygenase inhibition and vasomotor tone

1991 ◽  
Vol 261 (2) ◽  
pp. H443-H450 ◽  
Author(s):  
H. Toga ◽  
J. Usha Raj ◽  
R. Hillyard ◽  
B. Ku ◽  
J. Anderson

We have determined the sites of action of endothelin-1 (ET) in the lamb pulmonary circulation. The influence of cyclooxygenase inhibition and baseline vasomotor tone on ET effects was also studied. Lungs of 14 lambs (6-9 wk of age, 12.1 +/- 0.6 kg body wt) were isolated and perfused with blood. Group I lungs (n = 5) were untreated, group II lungs (n = 5) were treated with indomethacin to inhibit cyclooxygenase, and group III lungs (n = 4) were treated with indomethacin and a thromboxane A2 analogue, U-46619, to elevate vasomotor tone. All lungs were perfused with constant flow in zone 3, with left atrial and airway pressures being 8 and 6 cmH2O, respectively. We measured pulmonary arterial pressure and, by the micropuncture servo-null method, pressures in 20- to 50-microns diameter subpleural venules, both before and after each dose of ET was infused (50, 100, 250, and 500 ng/kg). Group I lungs, with high baseline vasomotor tone, exhibited a biphasic response to ET; 50-100 ng/kg of ET dilated both arteries and veins, whereas 500 ng/kg of ET constricted both arteries and veins. In group II lungs with low vasomotor tone, all doses of ET caused constriction of arteries only. In group III lungs (indomethacin treated with elevated vasomotor tone), 50-100 ng/kg of ET caused dilation of arteries and veins, whereas 500 ng/kg of ET induced constriction, this time only in arteries. We conclude that ET has both dilator and constrictor effects in arteries and veins of isolated, perfused lamb lungs. ET-induced arterial and venous dilation is dependent on initial vasomotor tone but not on cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

2004 ◽  
Vol 23 (8) ◽  
pp. 413-419 ◽  
Author(s):  
Cetin Kaymak ◽  
Ela Kadioglu ◽  
Hulya Basar ◽  
Semra Sardas

In this study, genotoxic effects of repeated sevoflurane anaesthesia were investigated in rabbits with or without antioxidant supplementation. Twenty-one New Zealand male rabbits were included in the study and randomized into three groups as: placebo treated (Group I), vitamin E supplemented (Group II) and selenium supplemented (Group III). Vitamin E and selenium were given intraperitoneally for 15 days before anaesthesia treatment. Anaesthesia was administered using 3% sevoflurane in 4 L/min oxygen for a 3-hour period and continued for 3 days. Blood samples were collected before anaesthesia (Sample 1), after the first, second and third days of sevoflurane administration (Sample 2, Sample 3 and Sample 4 respectively) and the last samples were taken 5 days after the last sevoflurane administration (Sample 5). Genotoxic damage was examined using the comet assay. The degree of damage is assessed by grading the cells into three categories of no migration (NM), low migration (LM) and high migration (HM) depending on the fraction of DNA pulled out into the tail under the influence of the electric field. The number of comets in each sample was calculated (1 × number of comets in category NM + 2 × number of comets in category LM + 3 ×number of comets in category HM) and expressed as the total comet score (TCS), which summarizes the damage frequencies. In Group I, a significant increase in the mean TCSs was observed for Samples 3 and 4 as compared with Sample 1. However, there were no significant differences between Samples 1, 2 and 5. The mean TCS of Sample 4 was significantly higher than Sample 1, 2 and 3 in Group II. Group III demonstrated no significant mean TCSs for any experimental conditions. Statistical differences were also observed between the groups with significant P values. This experimental study points out the presence of DNA damage with repeated sevoflurane anaesthesia and the genoprotective role of antioxidant supplementation on DNA damage in mononuclear leukocytes of rabbits by highly sensitive comet assay.


2021 ◽  
Author(s):  
Shivkumar Gopalakrishnan ◽  
sangeetha kandasamy ◽  
S.Malini ◽  
S.Peer Mohamed ◽  
k.velmurugan

Abstract Background. Approximately 5% of COVID-19 patients suffer near fatal disease. Clinical and radiologic features may predict severe disease albeit with limited specificity and radiation hazard. Laboratory biomarkers are eyed as simple, specific and point of care triage tools to optimize management decisions.This study aimed to study the role of inflammatory markers in prognosticating COVID-19 patients.Methodology. A hospital based retrospective study was conducted on COVID-19 adult inpatients classified into three groups as mild disease-recovered [Group I], severe disease-recovered [Group II] and dead [Group III]. Categorical outcomes were compared using Chi square test. Univariate binary logistic regression analysis was performed to test the association between the explanatory and outcome variables. Unadjusted OR along with 95% CI was calculated. The utility of lab parameters (Ferritin, LDH, D dimer, N/L ratio and PLT/L ratio) in predicting severity of COVID-19 was assessed by Receiver Operative Curve (ROC) analysis. P value < 0.05 was considered statistically significant.Results. The mean age was 49.32 +/- 17.1 years. Among study population, 378 were Group I, 66 Group II, and 56 Group III. Median levels of Ferritin among the 3 groups were 62ng/mL, 388.50 ng/mL and 1199.50 ng/mL. Median value of LDH were 95U/L, 720 and 982.50(p <0.001). D-dimer values of 3 groups were 23.20ng/mL, 104.30 ng/mL and 197.10 ng/mL (p <0.001). CRP done qualitatively was positive in 2 (0.53%), 30 (45.45%) and 53 (94.64%) of patients. The odds of patients suffering severe COVID-19 rose with rising values of ferritin, LDH and D-dimer [unadjusted OR 1.007, 1.004 &1.020]Conclusion. One time measurement of serum ferritin, LDH, D-dimer and CRP is promising to predict outcomes for COVID 19 inpatients. Single qualitative CRP was equally good but more cost effective than quantitative CRP. The most specific combination was NLR, Lymphocyte percentage and D-dimer levels done between 7th – 10th day of symptoms.


1995 ◽  
Vol 268 (4) ◽  
pp. H1510-H1520 ◽  
Author(s):  
C. van Hardeveld ◽  
V. J. Schouten ◽  
A. Muller ◽  
E. T. van der Meulen ◽  
G. Elzinga

The beneficial effect of low pH during cardiac ischemia on reperfusion injury has often been attributed to its energy-saving effect due to inhibition of contraction. The role of low pH on Ca2+ accumulation and muscle tension was assessed in energy-depleted tissue by changing the pH of the medium from 7.4 to 6.2 at onset of rigor development during metabolic inhibition (MI), i.e., in the energy-depleted phase. Cytosolic free Ca2+ ([Ca2+]i) and intracellular H+ (pHi) were measured in rat trabeculae at 20 degrees C with fura 2 and 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, respectively, and tension was recorded. The preparations were energy depleted by stimulation at 1 Hz in glucose-free Tyrode solution with 2 mM NaCN. Rigor developed within 20 min, indicating energy depletion. Resting [Ca2+]i was followed during 50 min (group I) or 100 min (group II) of rigor, and recovery was followed for 60 min in glucose-containing Tyrode solution at 0.2-Hz stimulation. Resting [Ca2+]i rose within 50 min (group I) but stabilized in the 50- to 100-min period (group II). All preparations from group I (n = 5) resumed contraction in the recovery period but in group II (n = 10) 70% failed to recover, and [Ca2+]i remained elevated compared with those that recovered. An extracellular pH of 6.2, resulting in similar pHi, from onset of rigor development (group III) led to only a modest rise in [Ca2+]i during the 100-min rigor period, and all preparations resumed contraction after approximately 3 min in normal medium. ATP was very low in all groups at the end of MI but was still significantly lower in group II than in groups I and III. A beneficial energy-sparing effect of low pH during the rigor phase can therefore not be excluded. We conclude that 1) the capacity of trabeculae to recover from MI depends on the time period and magnitude of the [Ca2+]i rise in the energy-depleted phase and 2) low pH in energy-depleted trabeculae protects against Ca overload, improving recovery after normalization of perfusion conditions.


1995 ◽  
Vol 268 (2) ◽  
pp. E248-E254 ◽  
Author(s):  
B. Capaldo ◽  
R. Napoli ◽  
R. Guida ◽  
P. Di Bonito ◽  
S. Antoniello ◽  
...  

The forearm perfusion technique was used 1) to quantify the muscle metabolism of glucose and gluconeogenic precursors in response to insulin-induced hypoglycemia and 2) to assess the role of catecholamines and glucose concentration, pe se. Insulin (0.5 mU.kg-1.min-1) was infused for 4 h in three groups of healthy volunteers. In group I (n = 6), blood glucose (BG) was maintained at its basal level (4.5 +/- 0.1 mmol/l). In group II (n = 7), BG was allowed to fall to approximately 3 mmol/l. Group III (n = 6) was similar to group II except that propranolol was infused also. In addition, at 240 min, hypoglycemia was locally corrected by intrabrachial glucose infusion while maintaining the systemic milieu unperturbed. In group I, forearm glucose uptake (FGU) increased from 4.7 +/- 1.3 to a mean value of 37.8 +/- 5.0 mumol.l-1.min-1, whereas in group II it remained unchanged (8.3 +/- 2.0 mumol.l-1.min-1). In group III, propranolol partially prevented the suppression of FGU that increased to 21.6 +/- 5.2 mumol.l-1.min-1 (P < 0.05 vs. group II). Local correction of hypoglycemia normalized the FGU response (36.5 +/- 8.0 mumol.l-1.min-1). Muscle release of lactate, but not of alanine, was slightly higher during hypoglycemia (P = not significant). Forearm blood flow remained unchanged in groups I and III, whereas it increased by approximately 40% in group II (P < 0.05). It is concluded that, during mild hypoglycemia 1) extreme insulin resistance develops in the skeletal muscle, mediated by beta-adrenergic stimulation and reduced glucose mass effect and 2) mobilization of gluconeogenic precursors is only weakly activated.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Carlo Bastianelli ◽  
Manuela Farris ◽  
Stefania Rapiti ◽  
Roberta Bruno Vecchio ◽  
Giuseppe Benagiano

Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis.Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated.Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion.Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates.


Author(s):  
Shyamala Nayak ◽  
Arun Kumar Nayanatara ◽  
Anupama Hegde ◽  
Rekha D Kini ◽  
Vandana Blossom ◽  
...  

Natural products are gaining much importance in light of the serious side effects posed by drugs of chemical origin. High intake of foods rich in antioxidants reduces the risk of neurodegenerative disorders. Traditionally, Allium sativum L.(garlic) and Allium cepa. L (onion) has received considerable attention for their therapeutic benefits around the globe. The present study assesses the free radical scavenging role of Allium sativum and Allium cepa in cerebral cortex, striatum, and hippocampus. Adult wistar rats of either sex were grouped as control group (Group I) treated with normal saline and the two experimental group were treated with the aqueous bulbous extracts of dehydrated Allium sativum (Group II) and Allium cepa (Group III) was considered as treated groups. Homogenates of hippocampus, striatum and cerebral cortex were analyzed for biochemical and neuronal analysis. LD50 value of these extracts in rats was found at a dose of 500 mg/kg BW. A Significant decline (P<0.05) in the MDA level was observed in the hippocampus, striatum and cerebral cortex in group II when compared to group III. Total antioxidant level, GSH, SOD level was significantly high (P<0.001) in the treated groups. Neuronal increase was significant in Group II (P < 0.01) when compared to Group III. Allium sativum and Allium cepa was found to have a challenging role in hampering oxidative stress in Hippocampus, striatum and cerebral cortex, the target regions in neurological disorders. However, ample number of studies are required to establish their mechanism of action as a progression to clinical approach.


Author(s):  
Arul Daniel J ◽  
Susmita Das ◽  
Neethu Jayan ◽  
Asha Devi S

Objectives: Various clinically available drugs along with the beneficial action also have drastic side effects due to chronic exposure. In liver, these resulting side effects can be over production of reactive oxygen species, which will further lead to oxidative stress and hepatotoxicity. Therefore, as a preventive measure, the protective role of herbal extracts is being evaluated because of its high success rate and low toxic effects. The primary aim of this study was to evaluate the efficiency of the protective role of Asparagus racemosus is evaluated and studied against methotrexate (MTX)-induced hepatic damage in male Wistar albino rats.Methods: The course of the study was for 14 days. During this experimental study, the animals were categorized into four groups with six rats per group. Group I (positive control) which was treated with normal saline, Group II (negative control) with MTX 20 mg/kg of body weight on 12th day, Group III with A. racemosus 300 mg/kg of body weight + MTX 20 mg/kg on 12th day, and Group IV with A. racemosus 100 mg/kg of body weight + MTX 20 mg/kg on 12th day. On 14th day, the animals were sacrificed, and histopathological as well as antioxidant assays were performed.Results and Conclusion: Assays revealed high lipid peroxidation level and low antioxidant levels in Group II. Meanwhile, in Group III and IV, the levels were restored near to control, which supported the protective role of A. racemosus against MTX-induced hepatic damage. Histopathology evaluation also supported the above-mentioned findings.


2011 ◽  
Vol 68 (12) ◽  
pp. 1021-1025
Author(s):  
Marija Igic ◽  
Dragan Mihailovic ◽  
Ljiljana Kesic ◽  
Mirjana Apostolovic ◽  
Ljiljana Kostadinovic ◽  
...  

Introduction/Aim. Gingivitis is a common occurrence in children and may well be thought as a risk factor for the appearance and progression of the diseases of parodontal tissues. It is thus necessary to react in a timely and adequate fashion to prevent the disease to become serious and produce parodontopathy. The aim of the study was to establish the efficacy of hyaluronic acid in the treatment of chronic gingivitis in children. Methods. The study enrolled 130 children with permanent dentition. All of the examinees were divided into three groups: group I - 50 patients with chronic gingivitis in which only the basic treatment was applied; group II - 50 patients with chronic gingivitis in which hyaluronic acid was applied in addition to basic treatment; group III - 30 examinees with healthy gingiva (control group). Assessment of oral hygiene and status of the gingiva and parodontium was done using the appropriate indexes before and after the treatment. Inflammation of the gingiva was monitored by way of cytomorphometric studies. Results. The pretreatment values of the plaque index (PI) were high: in the group I PI was 1.94; in the group II PI was 1.68. After the treatment, the PI value was reduced to null in both groups (PI = 0). In the group III PI was 0.17. The bleeding index (BI) in the group I was 2.02 before and 0.32 after the treatment; the BI value in the group II was 1.74 before and 0.16 after the treatment. In the group III BI was 0. In the group I, the Community Periodontal Index of Treatment Needs (CPITN) was 1.66 before and 0.32 after the treatment; in the group II, the CPITN value was 1.5 before and 0.24 after the treatment. In the group III, the CPITN value was 0. In the group I, the size of the nuclei of the stratified squamous epithelium of the gingiva was reduced, although not so much as the nuclear size in the group II of examinees. Conclusion. Basic treatment is able to successfully treat chronic gingivitis in children. The use of hyaluronic acid together with the basic treatment can markedly improve the treatment effect.


Author(s):  
Amita Coutinho ◽  
Neethu Reddy ◽  
Anirban Chatterjee ◽  
Mahamad Irfanulla Khan

AbstractVisfatin is an adipocytokine and a potential biomarker encoded by the nicotinamide phosphoribosyltransferase gene. It belongs to the nicotinic acid phosphoribosyltransferase family and involved in various metabolic processes and aging. The aim of this study was to evaluate the role of visfatin biomarker in oral diseases like periodontitis. A total of 60 patients (20–50 years) were included in this study, and they were divided into three groups. Group I consisted of 20 subjects with healthy periodontium, group II consisted of 20 subjects with generalized moderate gingivitis, and group III consisted of 20 subjects with generalized periodontitis. The clinical periodontal parameters, including plaque index, gingival index, probing pocket depth, and clinical attachment levels, were recorded, and saliva samples were collected. Salivary visfatin concentrations were assessed using standard enzyme-linked immunosorbent assay. The results of the study showed that the visfatin concentrations were higher in patients with gingivitis and periodontitis compared with those of healthy individuals. Visfatin was found highest in group III (38.22 ± 3.38 ng/mL) followed by group II (26.66 ± 2.24 ng/mL) and the group I (25.60 ± 2.19 ng/mL). Thus, salivary visfatin is a potential inflammatory biomarker and acts as a mediator in the pathogenesis of periodontal disease and, might serve as a diagnostic and therapeutic biomarker in oral diseases like periodontitis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Natalia S. Goncharova ◽  
Heber Ivan Condori Leandro ◽  
Aleksandr D. Vakhrushev ◽  
Elena G. Koshevaya ◽  
Yury A. Skorik ◽  
...  

Abstract Background Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine. Methods In this experimental sham-controlled study, 17 normotensive male white Landrace pigs (the mean weight 36.2 ± 4.5 kg) were included and randomly assigned to group I (n = 9)—PH modeling before and after PADN, group II (n = 4)—PADN only, or group III (n = 4)—PH modeling before and after a sham procedure. Radiofrequency (RF) PADN was performed in the PA trunk and at the proximal parts of the right and left PAs. PA wall lesions were characterized at the autopsy study using histological and the immunohistochemical examination. Results In groups I and II, no statistically significant changes in the mean pulmonary arterial pressure nor systemic blood pressure were found after PADN (−0.8 ± 3.4 vs 4.3 ± 8.6 mmHg, P = 0.47; and 6.0 ± 15.9 vs -8.3 ± 7.5 mmHg, P = 0.1; correspondingly). There was a trend towards a lower diastolic pulmonary arterial pressure after PADN in group I when compared with group III during repeat PH induction (34.4 ± 2.9 vs 38.0 ± 0.8; P = 0.06). Despite the presence of severe PA wall damage at the RF application sites, S100 expression was preserved in the majority of PA specimens. The presence of high-grade PA lesions was associated with HR acceleration after PADN (ρ = 0.68, p = 0.03). No significant correlation was found between the grade of PA lesion severity and PA pressure after PADN with or without PH induction. Conclusions Extended PADN does not affect PH induction using TXA2. Significant PA adventitia damage is associated with HR acceleration after PADN. Possible delayed effects of PADN on perivascular nerves and pulmonary hemodynamics require further research in chronic experiments.


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