Exposure of energy-depleted rat trabeculae to low pH improves contractile recovery: role of calcium

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.

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.


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)


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.


Author(s):  
S.K. Maiti ◽  
R. Tiwary ◽  
P. Vasan ◽  
A. Dutta

Thee different combinations of ketamine hydrochloride were used to induce general anaesthesia for surgical operations (typhlectomy) in 30 adult, single-comb White Leghorn cockerels. They were randomly divided into three groups, each comprising 10 birds. Birds in Group I received xylazine-ketamine combinations at the dose rate of 2 mg xylazine and 10 mg ketamine per kg i.v., whereas birds of Group II received diazepam (2.5 mg / kg i.v.) and 5 min later ketamine (75 mg / kg i.m.). In the Group III, midazolam (2 mg / kg i.m.) and 5 min later ketamine (50 mg / kg i.v.) was administered. The onset of sedation / anaesthesia was shortest (1.60 + 0.27 min) in Group I, followed by Group II (8.40 + 0.83 min) and Group III (17.10 + 1.71 min). Recovery period was shortest in the Group I (65-75 min) followed by Group II (80-85 min) and Group III (92-105 min). Sedation, muscle relaxation and surgical anaesthesia was optimal and excellent in Group I compared with the other two groups. Torticollis, salivation and dyspnoea were observed in Group III. Short-term limb contractions were present in all birds in Groups II and III, up to 20 min of observation. Recovery from anaesthesia was smooth in all three groups. A Surgical procedure (typhlectomy) was performed on all birds. Hypothermia was observed in Group II, whereas heart and respiratory depression was recorded in Group I. Blood sugar level did not vary significantly in any anaesthetic regime. The reduction of haemoglobin was maximum in Group II compared with Groups I and III. Hypoxaemia and hypercapnaea were elevated in all birds in Groups II and III. Blood electrolytes did not vary significantly from the baseline values among the three groups of birds during the period of observation (120 min). The xylazine-ketamine combination was found to be the best anaesthesia for surgical intervention in chickens.


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.


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.


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.


2020 ◽  
Vol 27 (09) ◽  
pp. 2023-2029
Author(s):  
Kumayl Abbas Meghji ◽  
Tariq Feroz Memon ◽  
Ahsan Aslam ◽  
Naila Noor ◽  
Ali Abbas ◽  
...  

Objectives: To evaluate the anti-oxidative role of Resveratrol in Cisplatin-induced testicular toxicity in Albino Wistar rats. Study Design: Quasi-experimental study. Settings: Department of Physiology and Postgraduate Laboratory of ISRA University Hyderabad. Period: Six months from March to September 2019. Material & Methods: Twenty-four male albino Wistar rats were distributed equally into; Group-I (Control), Group-II (Cisplatin), Group-III (Cisplatin + Resveratrol). Difference in mean pre and post-experimental body weight was observed while analysis of oxidative markers, semen parameters, and histomorphology was carried out in all three groups. SPSS ver. 22 was used to analyze the data. Results: The mean body weight decreased from 241.7±8.5 gm to 196.50±9.34 gm and from 237±7.4 gm to 210.0 ± 6.50gm in groups II and III respectively. Statistically significant reduction in semen parameters (sperm count, motility and viability) was observed in Group-II compared with Group-C (p<0.05). Oxidative markers were also significantly depleted in Group-II in comparison to Group-C (p<0.05). Histologically, testicular structure was found to be intact in Group-I. Marked changes were observed in testicular histology of Group-II while Group-III displayed less testicular damage. Irregular, regressive and atrophic seminiferous tubules were seen in Group-II. Most seminiferous tubules having normal morphology were observed in Group-III while the number of atrophic and degenerative seminiferous tubules also decreased significantly. Conclusion: Resveratrol therapy is a potent protective regime showing promising results in cisplatin-induced testicular toxicity and oxidative stress.


2020 ◽  
Author(s):  
Cezary Chojnacki ◽  
Marta Mędrek-Socha ◽  
Paulina Konrad ◽  
Jan Chojnacki ◽  
Aleksandra Błońska

Abstract Background Dyspeptic syndrome is particularly common in postmenopausal women in the form of epigastric pain. The aim of the study was to assess the role of melatonin in chronic dyspepsia in this group of women, and examine the role of Helicobacter infection.Methods The study comprised 152 subjects including 30 healthy women (Group I), 60 women with asymptomatic H.pylori infection (Group II), and 64 women with H. pylori infection with chronic dyspepsia (Group III). Endoscopic examination was performed, as well as histological assessment of gastric end duodenal mucosa, urease breath test (UBT-13C), and immunoenzymatic assessment of serum 17-β-estradiol, follicle stimulating hormone and melatonin, and urinary 6-sulfatoxymelatonin. In Group III, 14-day antibacterial treatment was introduced with pantoprazole, amoxicillin and levofloxacin followed a six-month treatment with placebo in 32 women (Group IIIa), and melatonin 1 mg/morning and 3 mg/at bedtime in the other 32 women (Group IIIb).Results No significant differences were found between serum level of female hormone. Serum melatonin levels were similar between Group I (12.5 ± 2.72pg/ml) and Group II (10.5±3.73 pg/ml; p>0,05). The level was significantly lower in Group III (5.72±1.42 pg/ml; p<0.001). Eradication of H.pylori was obtained in 75.0% women in Group IIIa, and in 84.3% in Group IIIb (p>0.05). After six months, dyspeptic symptoms resolved in 43.7% patients in Group IIIa and 84.3% in Group IIIb (p<0.001).Conclusion Melatonin supplementation is useful in treating H. pylori-associated dyspepsia, particularly in postmenopausal women with lower levels of this hormone.Trial registration: NCT04352062, date of registration: 15.04.2020.


Sign in / Sign up

Export Citation Format

Share Document