Effects of live high, train low hypoxic exposure on lactate metabolism in trained humans

2004 ◽  
Vol 96 (2) ◽  
pp. 517-525 ◽  
Author(s):  
Sally A. Clark ◽  
Robert J. Aughey ◽  
Christopher J. Gore ◽  
Allan G. Hahn ◽  
Nathan E. Townsend ◽  
...  
Keyword(s):  
Ph Regulation ◽  
Whole Body ◽  
Hypoxic Exposure ◽  
Protein Abundance ◽  
Lactate Metabolism ◽  
Hypoxia Exposure ◽  
Before And After ◽  
Resting Muscle

We determined the effect of 20 nights of live high, train low (LHTL) hypoxic exposure on lactate kinetics, monocarboxylate lactate transporter proteins (MCT1 and MCT4), and muscle in vitro buffering capacity (βm) in 29 well-trained cyclists and triathletes. Subjects were divided into one of three groups: 20 consecutive nights of hypoxic exposure (LHTLc), 20 nights of intermittent hypoxic exposure [four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia (LHTLi)], or control (Con). Rates of lactate appearance (Ra), disappearance (Rd), and oxidation (Rox) were determined from a primed, continuous infusion of l-[U-14C]lactic acid tracer during 90 min of steady-state exercise [60 min at 65% peak O2 uptake (V̇o2 peak) followed by 30 min at 85% V̇o2 peak]. A resting muscle biopsy was taken before and after 20 nights of LHTL for the determination of βm and MCT1 and MCT4 protein abundance. Ra during the first 60 min of exercise was not different between groups. During the last 25 min of exercise at 85% V̇o2 peak, Ra was higher compared with exercise at 65% of V̇o2 peak and was decreased in LHTLc ( P < 0.05) compared with the other groups. Rd followed a similar pattern to Ra. Although Rox was significantly increased during exercise at 85% compared with 65% of V̇o2 peak, there were no differences between the three groups or across trials. There was no effect of hypoxic exposure on βm or MCT1 and MCT4 protein abundance. We conclude that 20 consecutive nights of hypoxia exposure decreased whole body Ra during intense exercise in well-trained athletes. However, muscle markers of lactate metabolism and pH regulation were unchanged by the LHTL intervention.

DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo
Keyword(s):  
Thyroid Function Test ◽  
Normal Subjects ◽  
Adrenal Function ◽  
Function Test ◽  
Before And After ◽  
Adrenal Response ◽  
Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

scholarly journals DETERMINATION OF l-HISTIDINE IN NANOGRAM AMOUNTS AND THE QUESTION OF ITS OCCURRENCE IN MAST CELLS

1972 ◽  
Vol 20 (11) ◽  
pp. 917-922 ◽  
Author(s):  
DAVID I. WILKINSON ◽  
DAVID GLICK
Keyword(s):  
Mast Cells ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Peritoneal Mast Cells ◽  
Before And After ◽  
Chromatographic Detection ◽  
Rat Peritoneal Mast Cells ◽  
Rate Limiting

In an attempt to clarify the question of whether histidine is stored in the mast cell for coversion to histamine or whether the rate of conversion is rapid enough to prevent accumulation of histidine so that the rate-limiting step is the histidine uptake, it was found that no histidine was demonstrable in rat peritoneal mast cells by either quantitative analysis or paper chromatographic detection. Microadaptation of Hassall's method, based on conversion of l-histidine by histidase to urocanic acid and measurement of the latter by its absorbance at 277 nm, was made to permit determination of histidine in nanogram amounts in the presence of histamine. This adaptation was found reliable when compared with the o-phthalaldehyde method in estimation of l-histidine in serum and in insulin hydrolysate, and then it was applied to analysis of mast cells before and after l-histidine uptake in vitro. The adaptation should be generally useful in microanalysis of l-histidine in histologically and cytologically defined samples.

scholarly journals Hot-Stage Microscopy for Determination of API Particles in a Formulated Tablet

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Michal Šimek ◽  
Veronika Grünwaldová ◽  
Bohumil Kratochvíl
Keyword(s):  
Active Pharmaceutical Ingredient ◽  
Assessment Method ◽  
Hot Stage Microscopy ◽  
Tablet Disintegration ◽  
Before And After ◽  
In Vitro Assessment ◽  
Active Substances ◽  
Good Agreement

Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets.

Detection of allergen-induced airway hyperresponsiveness in isolated mouse lungs

2006 ◽  
Vol 291 (3) ◽  
pp. L466-L472 ◽  
Author(s):  
Martin Witzenrath ◽  
Birgit Ahrens ◽  
Stefanie M. Kube ◽  
Armin Braun ◽  
Heinz G. Hoymann ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Ex Vivo ◽  
Whole Body ◽  
Strongly Correlated ◽  
Ex Vivo Model ◽  
Isolated Lungs ◽  
Spontaneously Breathing

Airway hyperresponsiveness (AHR) is a hallmark of bronchial asthma. Important features of this exaggerated response to bronchoconstrictive stimuli have mostly been investigated in vivo in intact animals or in vitro in isolated tracheal or bronchial tissues. Both approaches have important advantages but also certain limitations. Therefore, the aim of our study was to develop an ex vivo model of isolated lungs from sensitized mice for the investigation of airway responsiveness (AR). BALB/c mice were sensitized by intraperitoneal ovalbumin (Ova) and subsequently challenged by Ova inhalation. In vivo AR was measured in unrestrained animals by whole body plethysmography after stimulation with aerosolized methacholine (MCh) with determination of enhanced pause ( Penh). Twenty-four hours after each Penh measurement, airway resistance was continuously registered in isolated, perfused, and ventilated lungs on stimulation with inhaled or intravascular MCh or nebulized Ova. In a subset of experiments, in vivo AR was additionally measured in orotracheally intubated, spontaneously breathing mice 24 h after Penh measurement, and lungs were isolated further 24 h later. Isolated lungs of allergen-sensitized and -challenged mice showed increased AR after MCh inhalation or infusion as well as after specific provocation with aerosolized allergen. AR was increased on days 2 and 5 after Ova challenge and had returned to baseline on day 9. AHR in isolated lungs after aerosolized or intravascular MCh strongly correlated with in vivo AR. Pretreatment of isolated lungs with the β2-agonist fenoterol diminished AR. In conclusion, this model provides new opportunities to investigate mechanisms of AHR as well as pharmacological interventions on an intact organ level.

A proinflammatory tumor that activates protein degradation sensitizes rats to catabolic effects of endotoxin

2005 ◽  
Vol 289 (4) ◽  
pp. E527-E533 ◽  
Author(s):  
Michelle L. Mackenzie ◽  
Nathalie Bedard ◽  
Simon S. Wing ◽  
Vickie E. Baracos
Keyword(s):  
Protein Degradation ◽  
Nitrogen Balance ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Ring Finger ◽  
Whole Body ◽  
Proteolytic Pathway ◽  
Before And After ◽  
Muscle Protein Degradation

Chronic or acute inflammation may participate in the etiology of cancer cachexia. To investigate the interaction between tumor and a secondary inflammatory stimulus on muscle wasting, rats with and without tumors (Yoshida ascites hepatoma) received low doses of endotoxin (LPS, 400 μg/kg sc) or saline. Nitrogen balance was measured 24 h before and after LPS/saline. Epitrochlearis muscle was used to measure in vitro protein metabolism, and gastrocnemius muscle was used for quantification of the mRNA for components of the ubiquitin proteolytic pathway. The YAH reduced muscle mass ( P = 0.002), increased muscle protein degradation ( P = 0.042), and elevated mRNA expression of components of the ubiquitin proteolytic pathway ( P < 0.01) including ubiquitin, ubiquitin-conjugating enzyme E214k, and ubiquitin ligases muscle RING Finger 1 and atrogin-1. Although the selected low dose of LPS had no impact on protein metabolism in control rats, LPS in rats bearing YAH caused weight loss ( P = 0.0007), lowered nitrogen balance ( P = <0.0001), and increased muscle protein degradation ( P = 0.0336). In conclusion, the presence of a tumor can potentiate whole body and muscle-specific catabolic losses of protein in response to a stimulus that is not catabolic in healthy animals. This effect might be dependent on the inflammatory nature of the tumor.

scholarly journals Evaluation of physicochemical and antioxidant properties of nanosized copolymeric micelles loaded with kaempferol

Pharmacia ◽  
2020 ◽  
Vol 67 (2) ◽  
pp. 49-54
Author(s):  
Krassimira Yoncheva ◽  
Nadia Hristova-Avakumova ◽  
Vera Hadjimitova ◽  
Trayko Traykov ◽  
Petar Petrov
Keyword(s):  
Antioxidant Activity ◽  
Propylene Oxide ◽  
Encapsulation Efficiency ◽  
Antioxidant Properties ◽  
In Vitro Release ◽  
Before And After ◽  
Poly Propylene ◽  
Vitro Release

The study was focused on the evaluation of two copolymers as micellar carriers for kaempferol delivery. The copolymers comprised identical hydrophilic blocks of poly(2-(dimethylamino)ethyl methacrylate and different hydrophobic blocks of either poly(ε-caprolactone) (PDMAEMA9-b-PCL70-b-PDMAEMA9) or poly(propylene oxide) (PDMAEMA13-b-PPO69-b-PDMAEMA13). The calculation of Flory-Huggins parameters and determination of encapsulation efficiency showed that PDMAEMA-b-PCL-b-PDMAEMA copolymer possessed higher capacity for kaempferol loading. The diameter of the micelles before and after lyophilization was not changed, suggesting that the micelles could be lyophilized and redispersed before administration. The in vitro release of kaempferol from PDMAEMA-b-PPO-b-PDMAEMA micelles was faster than the release from PDMAEMA-b-PCL-b-PDMAEMA micelles, probably due to the higher affinity of kaempferol to this copolymer. Further, the higher affinity resulted in a retention of antioxidant activity of kaempferol in the presence of DPPH and KO2 radicals. Thus, PDMAEMA-PCL-PDMAEMA was considered more appropriate carrier because of the higher encapsulation efficiency and preservation of antioxidant activity of the drug.

Letrozole suppresses plasma oestradiol (E2) levels more completely than anastrozole in postmenopausal women with breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 552-552 ◽  
Author(s):  
J. M. Dixon ◽  
L. Renshaw ◽  
O. Young ◽  
J. Murray ◽  
E. J. Macaskill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Complete Inhibition ◽  
Whole Body ◽  
Adjuvant Hormone Therapy ◽  
Case Methods ◽  
Highly Sensitive ◽  
Before And After ◽  
Estrogen Receptor Positive

552 Background: Letrozole (L) is a more potent aromatase inhibitor in vitro than anastrozole (A). One study in 12 patients showed that in patients L provides more complete inhibition of whole body aromatase and suppression of estrone sulphate levels than A but L did not significantly suppress E2 levels more than A possibly because of the small size of the study and the difficulty of measuring E2 in postmenopausal women (Geisler et al, JCO, 20, 751, 2002). The current aim was to conduct a much larger study to determine whether 2.5mg L suppresses E2 significantly more than 1mg A and if so in what proportion of patients this is the case. Methods: 54 postmenopausal women with invasive estrogen receptor positive breast cancer were randomised as part of their adjuvant hormone therapy to receive either: 12 weeks of L followed by 12 weeks of A (L→A) or 12 weeks of A followed by 12 weeks of L (A→L). Blood for hormones were taken at the same time of the day before and after 12 weeks of each drug. E2 was measured by a highly sensitive radioimmunoassay (Dowsett et al, Cancer Res 1987;47:1957–61) with a formal detection limit of 3pmol/l. In this study we also quantified values by extrapolation below this limit. Results: 27 patients had L→A and 27 A→L. Baseline E2 levels varied from 3 to 91 pmol/l with a median of 26 pmol/l. Only 1of 54 (2%) patients had an E2 value ≥ 3pmol/l after L compared with 20 of 54 (37%) after A(p <0.000005). After extrapolation, mean E2 level after A was 2.91 (SEM 0.18) pmol/l with a median of 2.70 pmol/l and after L was 1.76 (SEM 0.10) pmol/l with a median of 1.70 pmol/l (p<0.0001). Mean residual estradiol was 9.2% of baseline with A and 5.6% with L. Conclusions: This study has demonstrated unequivocally that the more complete inhibition of aromatase achieved by 2.5mg of letrozole than 1mg of anastrozole results in a greater degree of suppression of E2, the most bioactive oestrogen. [Table: see text]

DETERMINATION OF PA INHIBITOR 1 (PA INHIBITOR ACTIVITY AND PA INHIBITOR 1 ANTIGEN) IN PLASMA BEFORE AND AFTER VENOUS OCCLUSION

1987 ◽  
Author(s):  
I Juhan-Vague ◽  
J Valadier ◽  
M C Alessi ◽  
J Ansaldi ◽  
M F Ailluad ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Venous Occlusion ◽  
Inhibitor Activity ◽  
Post Surgery ◽  
In Vitro Activation ◽  
Before And After ◽  
High Level ◽  
Good Preparation

PA Inhibitor activity (PAIact-Verheijen’s method-U/ml) and PA Inhibitor 1 antigen (PAIlAg- Kruithof’s radioimmunoassay -ng/ml) were evaluated, on blood samples before (B) and after (A) venous occlusion (VO) (10 min) in order to analyse, in B-VO samples, the ratio (R=PAIlAg/PAIact) ' between the immunological and enzymatic material, and the change of PAIlAg levels after VO.The B-VO values (m ± SD) were determined from 111 plasmas : -86 with normal ( 12U/ml) PAIact levels = 3.7 ± 2.5 ; PAIlAg = 17.4 ± 10.1 ; R = 7.1 ± 6.2 (range 1.5 - 24 )-25 with high PAIact levels (15 post surgery, 10 obese patients)= 30.9± 19.3; PAIlAg = 75.3 ± 44.7 ; R = 2.7 ± 1.5 (range 1.3- 4.4). The correlation between the 2 dosages was r = 0.82 (p 0.01). In the 2 kinds of patients with high PAIact levels, a parallel high PAIlAg level was found. As the range of the ratio R was very large, patients were divided in 2 Groups : GrI : Normal R ( 7), n=81 (normal PAIact : n=57 ; high PAIact : n=24) and GrII : high R, n=30. The results for PAIact/PAIlAg/R were = GrI :12.6± 16.3/ 31.5±34.4/ 3.2 ± 1.5. GrII : 2.6±4.1/ 27.9 ±30.1/ 13.8±6.1. In GrII the platelet origin of inactive PAIlAg from in vitro activation of platelets could be demonstrated (high level of BTG lug/ml) in 50 % of cases. No in vitro platelet activation could be demonstrated in GrI. These results point out the necessity of a good preparation of the plasma (mainly 0-4°) for PAIlAg determination.The B and A-VO values were analysed from 60 subjects. Plasmas with in vitro activation of platelet determined by BTG levels had been discarded. No platelet activation occured with the VO. The results were not corrected with the PCV. PAIlAg B-VO/A-VO = 19.2 ± 15.1/ 26.9 ± 18.3. 36 subjects (60 % of total) had an increase in PAIlAg A-VO 20 % (mean increase = 62 %) . There was no correlation between basal values of PAIlAg and the increase after VO, and between PAIlAg increase and t-PA-Ag release. It is concluded that a weak increase of PAIlAg may occur after VO ; this increase is not parallel with t-PA release. The physiopathological significance of this increase of PAIlAg as yet to be evaluated.

scholarly journals PENENTUAN PROFIL ELUSI IODIUM-125 SEBAGAI PERUNUT UNTUK TUJUAN RADIOIMMUNIASSAY (RIA)

2016 ◽  
Vol 17 (2) ◽  
pp. 59
Author(s):  
Maiyesni Maiyesni ◽  
Mujinah Mujinah ◽  
Dede Kurniasih ◽  
Witarti Witarti ◽  
Triyatno Triyatno ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
Elution Profile ◽  
Alkaline Ph ◽  
Dose Calibrator ◽  
Purity Level ◽  
Before And After ◽  
Preliminary Study ◽  
Iodine 125

Manfaat iodium-125 (125-I) sudah banyak diketahui. 125-I  dapat digunakan antara lain sebagai perunut dalam teknik Radioimmunoassay (RIA) untuk deteksi dini berbagai penyakit kanker, menentukan kesuburan hewan ternak serta cemaran mikotoksin di dalam pangan secara invitro.  125-I  yang dibutuhkan dalam teknik ini disamping harus mempunyai kemurnian radiokimia > 95%,  konsentrasi radioaktifitas   juga tinggi, sehingga volume  125-I  haruslah sekecil mungkin. Dengan demikian perlu dipelajari profil elusi 125-I dari kolom reduktor Jones saat proses peningkatan kemurnian  radiokimia. Penelitian ini bertujuan untuk menentukan volume optimal  eluat dengan efisiensi dan kemurnian radiokimia yang dapat diterima. Pada penelitian ini kondisi kolom yang dipilih adalah kolom dengan pH basa. Kolom reduktor Jones yang mengandung  125-I dielusi dengan larutan  NaOH 0,01N secara  fraksinasi volume 1 ml. Radioaktifitas  masing-masing fraksi diukur menggunakan  dose calibrator. Penentuan kemurnian radiokimia dilakukan pada fraksi yang memiliki radioaktifitas  tertinggi dan fraksi gabungan  dengan  metode kromatografi kertas. Radioaktifitas  tertinggi ditunjukkan pada  fraksi kedua  yaitu  16,59  mCi dengan efisiensi 33,95% dan fraksi gabungan yaitu 50,19 mCi dengan efisiensi 92,26%. Kemurnian radiokimia 125-I bulk, fraksi kedua dan fraksi gabungan berturut-turut adalah 41,50, 97,5  dan  98,50%.  Volume optimal eluat adalah 7 ml serta  pH 125-I sebelum dan sesudah fraksinasi adalah 10 -11.  Determination of  Elution Profile the Iodine-125 as a tracer for Radioimmunoassay (RIA). The benefits of the Iodine-125 (125I ) isotope was well known. 125I are used as radiotracer in Radioimmunoassay (RIA) technique for early detection of cancer, determine of hormone content which related with fertility of livestock and also for contamination detection of mycotoxins on food by in vitro.  125I which is needed in this technique not only must have high radiochemical purity above 95% but also high radioactivity concentration, so that  125I volume which is use must as little as possible. Therefore, 125I elution profile for increasing radiochemical purity using a reductor Jones column should be studied. Aim of this study is to determine the optimum volume of eluate which have efficiency and radiochemical purity that can be accepted. The preliminary study was conducted to determine the optimal conditions of reductor Jones  column. Reductor Jones column is conditioned on neutral and alkaline pH. At this elution study, the columns conditions selected is alkaline pH. Reductor Jones column which containing 125I eluted with NaOH 0,01 N solution by fractionated in 1mL. The radioactivity of each fraction is measured with dose calibrator.  Determination of the radiochemical purity of carried out on the fraction which have the highest radioactivity and the combined fractions using paper chromatography. Highest radioactivity is shown in the second fraction at 16,59 mCi with efficiency 33,95%  and combined fractions at 50,19 mCi with efficiency 92,26%. The radiochemical purity of 125-I bulk, second fraction and combined fractions are 41,50%, 97,5 % dan  98,50%, respectively.  Optimum fraction is 7 mL and pH of 125-I before and after fractination are 10-11. By studying the elution profile can be known that the optimal volume is the smallest total volume of eluent with efficiency and radiochemical purity level that can be accepted. 

Effect of Maintained Hypoxic Exposure on the Crayfish Orconectes Rusticus: II. Modulation of Haemocyanin Oxygen Affinity

1982 ◽  
Vol 98 (1) ◽  
pp. 139-149
Author(s):  
P.R. H. WILKES ◽  
B. R. McMAHON
Keyword(s):  
Oxygen Affinity ◽  
Respiratory Alkalosis ◽  
Hypoxic Exposure ◽  
Protein Levels ◽  
Ambient Oxygen ◽  
Before And After ◽  
Acid Base Status ◽  
Oxygen Carrying Capacity

Haemolymph Na+, Cl−, K+, Mg2+, Ca2+, Cu2+ and protein levels, in vivo postbranchial acid-base status (total CO2, pH and PCOCO2), in vitro haemolymph buffer value, Bohr value and oxygen affinity were measured before and after a 3½-week period in which control crayfish were maintained at normoxia and experimental crayfish were maintained at an ambient oxygen tension of 50-55 torr. Analysis of haemolymph Cu2+ and protein levels in control and experimental crayfish indicated no increase in haemocyanin and therefore oxygen carrying capacity of the haemolymph. Although the Bohr value was not significantly different between control and experimental crayfish, the haemocyanin oxygen affinity was elevated in the hypoxic crayfish by two mechanisms. The first was dependent upon the haemolymph H+ concentration, i.e. a Bohr shift resulting from a respiratory alkalosis. The second mechanism was independent of haemolymph H+ concentration in that at a given pH haemolymph from experimental crayfish had a significantly higher oxygen affinity. The decrease in p50 probably cannot be attributed to a specific cation effect.

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