Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice

2002 ◽  
Vol 283 (6) ◽  
pp. C1776-C1783 ◽  
Author(s):  
Brian B. Roman ◽  
Ronald A. Meyer ◽  
Robert W. Wiseman

Phosphocreatine (PCr) depletion during isometric twitch stimulation at 5 Hz was measured by31P-NMR spectroscopy in gastrocnemius muscles of pentobarbital-anesthetized MM creatine kinase knockout (MMKO) vs. wild-type C57B (WT) mice. PCr depletion after 2 s of stimulation, estimated from the difference between spectra gated to times 200 ms and 140 s after 2-s bursts of contractions, was 2.2 ± 0.6% of initial PCr in MMKO muscle vs. 9.7 ± 1.6% in WT muscles (mean ± SE, n = 7, P < 0.001). Initial PCr/ATP ratio and intracellular pH were not significantly different between groups, and there was no detectable change in intracellular pH or ATP in either group after 2 s. The initial difference in net PCr depletion was maintained during the first minute of continuous 5-Hz stimulation. However, there was no significant difference in the quasi-steady-state PCr level approached after 80 s (MMKO 36.1 ± 3.5 vs. WT 35.5 ± 4.4% of initial PCr; n = 5–6). A kinetic model of ATPase, creatine kinase, and adenylate kinase fluxes during stimulation was consistent with the observed PCr depletion in MMKO muscle after 2 s only if ADP-stimulated oxidative phosphorylation was included in the model. Taken together, the results suggest that cytoplasmic ADP more rapidly increases and oxidative phosphorylation is more rapidly activated at the onset of contractions in MMKO compared with WT muscles.

2021 ◽  
Vol 14 (3) ◽  
pp. 235
Author(s):  
Jen-Sheng Pei ◽  
Chao-Chun Chen ◽  
Wen-Shin Chang ◽  
Yun-Chi Wang ◽  
Jaw-Chyun Chen ◽  
...  

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08–2.14, p = 0.0429) and 1.94 (95%CI, 1.15–3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13–1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14511-14511 ◽  
Author(s):  
S. Hazama ◽  
H. Koudo ◽  
S. Yoshida ◽  
R. Shimizu ◽  
H. Ozasa ◽  
...  

14511 Background: We have presented at 2006 ASCO annual meeting about a genetic UGT1A1 polymorphism oriented phase (P) I study of Irinotecan and 5’-DFUR for metastatic colorectal cancer (MCRC) to determine the maximum tolerated dose (MTD) and the recommend doses (RD) for each UGT1A1 *1/*1 and *1/*28 genotypes. The RD of biweekly Irinotecan administration was 150 mg/m2 for patients (pts) with wild *1/*1 genotype and 70 mg/m2 of Irinotecan for mutated *1/*28. Now we are carrying out a *28 oriented P II study based on this RD. Here we report the profiles of toxicities in the P II study of irinotecan and 5’-DFUR to analyze other kinds of UGT1As polymorphisms in relation to irinotecan toxicities. Patients & Methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–1, age<76, adequate organ functions, and written informed consent. Twenty one pts with wild type genotype and 9 pts with mutated genotype were enrolled. Irinotecan was infused 150 mg/m2 for pts with *1/*1 genotype and 70 mg/m2 for *1/*28. Hematological and non-hematological toxicities were graded, and UGT1As polymorphisms (UGT1A1*6 and *7, UGT1A7*1*2*3*4, UGT1A9*22) were analyzed. Results: Grade (G)3 & 4 toxicities were observed in 6 of 22 (27%) wild type pts and in 3 of 9 (33%) mutated pts, and in 9 of 31 (29%) all pts. There was no significant difference on the profiles of toxicities between the pts with wild genotype and mutated genotype, irrespective of the difference of the quantity of irinotecan. So, the RD was thought to be adequate. In pts with UGT1A1*6 allele, G3 & 4 toxicities were observed 6/11 (55%), on the other hand 3/20 (15%) in pts without *6 allele (p=0.038). G3 & 4 toxicities were also more frequent in pts with UGT1A7*3 alleles than pts without *3 allele (p<0.10). Conclusions: The profiles of toxicities of pts with *1/*1 or *1/*28 genotypes were similar irrespective of the difference of the quantity of irinotecan. The result indicated that the RD of latest PI for each group was adequate, and this P II study is suitable to analyze other kinds of polymorphisms that have correlation to irinotecan toxicities. UGT1A1*6 and UGT1A7*3 allele will be a novel predictor for toxicity of irinotecan. No significant financial relationships to disclose.


1999 ◽  
Vol 67 (8) ◽  
pp. 3757-3762 ◽  
Author(s):  
Stacy M. Burns ◽  
Sheila I. Hull

ABSTRACT To determine the importance of the O75 O antigen and the K5 capsular antigen in resistance to phagocytosis and phagocytic killing, we used previously described O75− and K5−mutants from an O75+ K5+ wild-type uropathogenic Escherichia coli strain in phagocytosis assays with polymorphonuclear leukocytes (PMNs) and monocytes. At a 10-to-1 ratio of bacteria to phagocytes and in the presence of 10% serum, the parental strain GR-12 was resistant to both PMNs and monocytes over a 2-h incubation period. The O75− and K5− mutants were similar in sensitivity to killing by both PMNs and monocytes, decreasing in viability by 80% in the first hour. Yet, a significant difference in killing between the O75−and K5− mutants was observed in the first 15 min of incubation. The K5− mutant decreased in numbers by almost 60%, while the O75− mutant increased in numbers similarly to GR-12 in the first 15 min. The difference in killing was found not to be due to the rate of opsonization. To further determine the mechanism of resistance, a fluorescence assay was used to differentiate attached and internalized bacteria. The K5 capsule hindered the association of both the wild-type strain and the O75−mutant in the initial incubation time with PMNs. In conclusion, both the K5 capsule and O75 O antigen play crucial roles in resistance to phagocytosis over time.


2008 ◽  
Vol 294 (2) ◽  
pp. E326-E335 ◽  
Author(s):  
Jin Xu ◽  
Li Zhang ◽  
Andrew Chou ◽  
Tim Allaby ◽  
Guy Bélanger ◽  
...  

In wild-type mice, a single injection of streptozotocin (STZ, 200 mg/kg body wt) caused within 4 days severe hyperglycemia, hypoinsulinemia, significant glucose intolerance, loss of body weight, and the disappearance of pancreatic β-cells. However, in ATP-sensitive K+ channel (KATP channel)-deficient mice (Kir6.2−/− mice), STZ had none of these effects. Exposing isolated pancreatic islets to STZ caused severe damage in wild-type but not in Kir6.2−/− islets. Following a single injection, plasma STZ levels were slightly less in Kir6.2−/− mice than in wild-type mice. Despite the difference in plasma STZ, wild-type and Kir6.2−/− liver accumulated the same amount of STZ, whereas Kir6.2−/− pancreas accumulated 4.1-fold less STZ than wild-type pancreas. Kir6.2−/− isolated pancreatic islets also transported less glucose than wild-type ones. Quantification of glucose transporter 2 (GLUT2) protein content by Western blot using an antibody with an epitope in the extracellular loop showed no significant difference in GLUT2 content between wild-type and Kir6.2−/− pancreatic islets. However, visualization by immunofluorescence with the same antibody gave rise to 32% less fluorescence in Kir6.2−/− pancreatic islets. The fluorescence intensity using another antibody, with an epitope in the COOH terminus, was 5.6 times less in Kir6.2−/− than in wild-type pancreatic islets. We conclude that 1) Kir6.2−/− mice are STZ resistant because of a decrease in STZ transport by GLUT2 in pancreatic β-cells and 2) the decreased transport is due to a downregulation of GLUT2 activity involving an effect at the COOH terminus.


2020 ◽  
Vol 139 ◽  
pp. 93-102 ◽  
Author(s):  
MF Van Bressem ◽  
P Duignan ◽  
JA Raga ◽  
K Van Waerebeek ◽  
N Fraijia-Fernández ◽  
...  

Crassicauda spp. (Nematoda) infest the cranial sinuses of several odontocetes, causing diagnostic trabecular osteolytic lesions. We examined skulls of 77 Indian Ocean humpback dolphins Sousa plumbea and 69 Indo-Pacific bottlenose dolphins Tursiops aduncus, caught in bather-protecting nets off KwaZulu-Natal (KZN) from 1970-2017, and skulls of 6 S. plumbea stranded along the southern Cape coast in South Africa from 1963-2002. Prevalence of cranial crassicaudiasis was evaluated according to sex and cranial maturity. Overall, prevalence in S. plumbea and T. aduncus taken off KZN was 13 and 31.9%, respectively. Parasitosis variably affected 1 or more cranial bones (frontal, pterygoid, maxillary and sphenoid). No significant difference was found by gender for either species, allowing sexes to be pooled. However, there was a significant difference in lesion prevalence by age, with immature T. aduncus 4.6 times more likely affected than adults, while for S. plumbea, the difference was 6.5-fold. As severe osteolytic lesions are unlikely to heal without trace, we propose that infection is more likely to have a fatal outcome for immature dolphins, possibly because of incomplete bone development, lower immune competence in clearing parasites or an over-exuberant inflammatory response in concert with parasitic enzymatic erosion. Cranial osteolysis was not observed in mature males (18 S. plumbea, 21 T. aduncus), suggesting potential cohort-linked immune-mediated resistance to infestation. Crassicauda spp. may play a role in the natural mortality of S. plumbea and T. aduncus, but the pathogenesis and population level impact remain unknown.


2018 ◽  
Vol 1 (2) ◽  
pp. 114
Author(s):  
Wahdaniah Wahdaniah ◽  
Sri Tumpuk

Abstract: Routine blood examination is the earliest blood test or screening test to determine the diagnosis of an abnormality. Blood easily froze if it is outside the body and can be prevented by the addition of anticoagulants, one of which Ethylene Diamine Tetra Acetate (EDTA). Currently available vacuum tubes containing EDTA anticoagulants in the form of K2EDTA and K3EDTA. K3EDTA is usually a salt that has better stability than other EDTA salts because it shows a pH approaching a blood pH of about 6.4. The purpose of this research is to know the difference of erythrocyte index results include MCH, MCV and MCHC using K3EDTA anticoagulant with K2EDTA. This research is a cross sectional design. This study used venous blood samples mixed with K2EDTA anticoagulant and venous blood mixed with K3EDTA anticoagulants, each of 30 samples. Data were collected and analyzed using paired different test. Based on data analysis that has been done on MCH examination, p value <0,05 then there is a significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value. Then on the examination of MCV and MCHC obtained p value <0.05 then there is no significant difference between samples with K3EDTA anticoagulant with K2EDTA to erythrocyte index value.Abstrak: Pemeriksaan darah rutin merupakan pemeriksaan darah yang paling awal atau screening test untuk mengetahui diagnosis suatu kelainan. Darah mudah membeku jika berada diluar tubuh dan bisa dicegah dengan penambahan antikoagulan, salah satunya Ethylene Diamine Tetra Acetate (EDTA). Dewasa ini telah tersedia tabung vakum yang sudah berisi antikoagulan EDTA dalam bentuk  K2EDTA dan  K3EDTA. K3EDTA  biasanya berupa garam yang mempunyai stabilitas yang lebih baik dari garam EDTA yang lain karena menunjukkan pH yang mendekati pH darah yaitu sekitar 6,4. Tujuan dari penelitian ini adalah untuk mengetahui perbedaan hasil indeks eritrosit meliputi MCH, MCV dan MCHC menggunakan antikoagulan K3EDTA dengan K2EDTA. Penelitian ini merupakan penelitian dengan desain cross sectional. Penelitian ini menggunakan sampel darah vena yang dicampur dengan antikoagulan K2EDTA dan darah vena yang dicampur dengan antikoagulan K3EDTA, masing-masing sebanyak 30 sampel. Data dikumpulkan dan dianalisis menggunakan uji beda berpasangan. Berdasarkan analisis data yang telah dilakukan pada pemeriksaan MCH didapatkan nilai p < 0,05 maka ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit. Kemudian pada pemeriksaan MCV dan MCHC didapatkan nilai p < 0,05 maka tidak ada perbedaan yang signifikan antara sampel dengan antikoagulan K3EDTA dengan K2EDTA terhadap nilai indeks eritrosit.


2017 ◽  
Vol 1 (1) ◽  
pp. 89
Author(s):  
Indah Purwaningsih ◽  
Supriyanto Supriyanto

Abstract: Chlorine is a green halogen-shaped halogen gas at normal temperature and serves as bleach, stain remover and disinfectant. Chlorine is now widely used for bleaching rice so that less quality rice looks like quality rice. Chlorine is very toxic and causes mucous membrane irritation, highly reactive and very powerful oxidizer. The purpose of this research was to determine the difference of chlorine level in chlorinated rice washed once, twice and 3 times. The sample in this study amounted to 11 samples calculated by replication formula. Each sample was treated 3 times, ie 1 washed once, 2 washed twice and washed 3 times. The samples then examined by iodometric titration method. Based on the results of the study using ANOVA test, 11 samples obtained the average value of chlorine after washed once amount of 0.0176%, after washed twice amount of 0.0111%, and after washed 3 times amount of 0.0052% with the value significance p = 0.03 (p <0.05) at 95% confidence level which means there was a significant difference between chlorine levels in chlorinated rice washed once, twice and 3 times.Abstrak: Klorin merupakan unsur halogen berbentuk gas berwarna kuning kehijauan pada suhu normal danberfungsi sebagai pemutih, penghilang noda maupun desinfektan. Klorin sekarang banyak digunakan untuk bahan pemutih beras agar beras yang kurang berkualitas tampak seperti beras berkualitas. Klorin sangat toksik dan menyebabkan iritasi membran mukosa, sangat reaktif dan merupakan oksidator yang sangat kuat. Tujuan dari penelitian ini ialah untuk mengetahui perbedaan kadar klorin pada beras berklorin yang dicuci sebanyak 1 kali, 2 kali dan 3 kali. Sampel dalam penelitian ini berjumlah 11 sampel yang dihitung dengan rumus replikasi. Setiap sampel diberi perlakuan sebanyak 3 kali, yaitu 1 kali pencucian, 2 kali pencucian dan 3 kali pencucian. Sampel penelitian kemudian diperiksa dengan metode titrasi iodometri. Berdasarkan hasil penelitian menggunakan uji Anova secara komputerisasi terhadap 11 sampel diperoleh nilai rata-rata kadar klorin setelah 1 kali pencucian sebesar 0,0176 %, setelah 2 kali pencucian sebesar 0,0111 %, dan setelah 3 kali pencucian sebesar 0,0052 % dengan nilai signifkansi p = 0,03 (p<0,05) pada tingkat kepercayaan 95% yang artinya ada perbedaan yang bermakna antara kadar klorin pada beras berklorin yang dicuci sebanyak 1 kali, 2 kali dan 3 kali.


1985 ◽  
Vol 17 (11-12) ◽  
pp. 325-326 ◽  
Author(s):  
H J. G. W. Donker ◽  
P. Opic ◽  
H. P. de Vries

Ca. 60 % of the Dutch activated sludge plants consist of completely mixed systems, experiments have been carried out in completely mixed pilot plants to study the biological P-removal. The research was carried out in two pilot plants. The pilot plants consisted of: anaerobic reactor, anoxic reactor, aerobic reactor and a clarifier. All the reactors were completely mixed. Both plants were fed with settled domestic waste water at a sludge loading of 400 and 250 g COD/kg sludge.day respectively. The results are given below:sludge loading (g COD/kg sludge.day)400400250ratio Anaerobic : Anoxic : Aerobic1: 1:2,71:1:4,11:1:2,7P-removal (%)802875N-removal (%)505065COD-removal (%)858585 It has been shown that there is no significant difference between the results at the two different sludge loadings. Remarkable is the difference between the ratio 1:1:2,7 in combination with the internal recirculation flow anoxic-anaerobic of 160 % and the ratio 1:1:4,1 with a recirculation flow of 30 %. During the start-up at a sludge loading of 250 g COD/kg sludge.day and an internal recirculation flow of 30 %, bulking sludge developed almost immediately. The Premoval was completely disturbed. Increasing the internal recirculation flow to 160% had a positive effect on settling properties and P-removal. This investigation has pointed out that a completely mixed system is suitable for biological P-removal, without negatively affecting the nitrification. Important factors in the process are the ratio anaerobic:anoxic:aerobic and the recirculation flows.


2019 ◽  
Vol 19 (9) ◽  
pp. 699-703
Author(s):  
Shihao Zhou ◽  
Qiong Zhan ◽  
Xiaomei Wu

Background: This study aimed to explore the clinical effect of levetiracetam in the treatment of children with epilepsy. Methods: 136 children with epilepsy were selected from January 2017 to December 2017. According to the random number table method, they were divided into the experimental group and the conventional group, with 68 cases in each group. The conventional group was treated with valproate, while the experimental group was treated with levetiracetam. The effective rate, the cognitive function and the frequency of clonic seizures in the two groups were compared. Results: There was no significant difference in the total effective rate between the two groups (P>0.05). There was no significant difference in attention, executive ability, abstract and orientation scores between the two groups before treatment (P>0.05). After treatment, the focus of attention (106.54±6.56), executive ability (105.76±6.77), abstract and directional score (106.65±6.57) were significantly higher than that of the conventional group. The difference in the two groups was statistically significant (P<0.05). After 3 months of treatment, the frequency of myoclonic seizures (9.22±0.95) and the frequency of tonic-clonic seizures (11.68±1.36) were found to be significantly lower than those of the conventional group, and the difference between the two groups was statistically significant (P<0.05). Conclusion: Levetiracetam is effective in the treatment of children with epilepsy. It can effectively improve the cognitive function of the patients, reduce the frequency of myoclonic seizures and tonic-clonic seizures, and has a high promotion value.


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