Erythrocyte cation fluxes during the menstrual cycle in normal female subjects

1987 ◽  
Vol 73 (2) ◽  
pp. 223-226 ◽  
Author(s):  
J. C. Monaghan ◽  
D. A. Willcocks ◽  
M. J. Sinosich ◽  
G. S. Stokes

1. Studies of erythrocyte cation transport mechanisms in vitro were performed on eight normotensive, premenopausal female subjects at the mid-points of the follicular and luteal phases of their menstrual cycles. Concurrent plasma concentrations of 17β-oestradiol, progesterone, aldosterone and renin activity were measured. 2. Ouabain-resistant, frusemide-resistant rubidium influx (an index of passive potassium diffusion) was significantly lower in the luteal than the follicular phase. 3. In further studies in four of the eight subjects, the mean rate constant of the rubidium influx measurement was also lower in the luteal than in the follicular phase. 4. There were no changes in Na+-K+ co-transport, sodium pump activity or intracellular cation concentrations throughout the cycle. 5. There was a tenfold fall in the mean plasma 17β-oestradiol/progesterone ratio, as well as increases in plasma aldosterone concentration and renin activity between the mid-follicular and mid-luteal phases. 6. We conclude that changes in plasma oestrogen/progesterone ratio during the menstrual cycle may be associated with alterations in passive potassium diffusion.

1982 ◽  
Vol 62 (2) ◽  
pp. 183-191 ◽  
Author(s):  
K. E. L. McColl ◽  
A. M. Wallace ◽  
M. R. Moore ◽  
G. G. Thompson ◽  
A. Goldberg

1. The timing of onset of attacks of acute intermittent porphyria (AIP) in relation to the menstrual cycle has been studied in three patients experiencing frequent attacks. Nineteen of their 27 admissions in attack for which no exogenous precipitating causes could be identified were during the 7 days before the onset of menstruation. 2. Haem biosynthesis has been monitored throughout a complete menstrual cycle in six normal females and compared with that in male control subjects. In the females, there was marked fluctuation in the activity of the rate-controlling enzyme of haem biosynthesis, δ-aminolaevulinate (ALA) synthase, which was monitored in peripheral leucocytes. The fluctuation did not show any clear association with menstruation and no association was found between the enzyme activity and ovarian or adrenal steroid production as monitored by measurement of plasma concentrations of androstenedione, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, oestradiol and progesterone. The activity of uroporphyrinogen I (URO) synthase, the enzyme which is deficient in AIP, was monitored in peripheral erythrocytes of four of the normal female subjects and was similar to that found in four male control subjects. The urinary excretion of ALA and porphobilinogen (PBG) was also similar in the male and female subjects and there was no association with the phase of the menstrual cycle or activity of the enzymes studied. 3. Studies of haem biosynthesis have been made throughout a complete menstrual cycle in a 26 year old female with latent AIP. The activity of leucocyte ALA synthase showed more marked fluctuation than in the normal female subjects and was highest at the time of menstruation. No association was apparent between the activity of ALA synthase and plasma concentrations of androstenedione, DHA and DHAS. The fluctuation in activity of erthrocyte URO synthase was similar to that of the normal subjects. The urinary excretion of ALA and PBG was normal throughout and showed no correlation with fluctuations in enzyme activity. 4. The human menstrual cycle modifies haem biosynthesis in normal subjects as well as in subjects with latent and manifested AIP. 5. The human female menstrual cycle modifies haem biosynthesis in peripheral blood cells as well as in the liver.


2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Iris H. Chen ◽  
David P. Nicolau ◽  
Joseph L. Kuti

ABSTRACT Combination therapy may enhance imipenem/cilastatin/relebactam’s (I/R) activity against Pseudomonas aeruginosa and suppress resistance development. Human-simulated unbound plasma concentrations of I/R at 1.25 g every 6 h (h), colistin at 360 mg daily, and amikacin at 25 mg/kg daily were reproduced alone and in combination against six imipenem-nonsusceptible P. aeruginosa isolates in an in vitro pharmacodynamic model over 24 h. For I/R alone, the mean reductions in CFU ± the standard errors by 24 h were −2.52 ± 0.49, −1.49 ± 0.49, −1.15 ± 0.67, and −0.61 ± 0.10 log10 CFU/ml against isolates with MICs of 1/4, 2/4, 4/4, and 8/4 μg/ml, respectively. Amikacin alone also resulted in 24 h CFU reductions consistent with its MIC, while colistin CFU reductions did not differ. Resistant subpopulations were observed after 24 h in 1, 4, and 3 I/R-, colistin-, and amikacin-exposed isolates, respectively. The combination of I/R and colistin resulted in synergistic (n = 1) or additive (n = 2) interactions against three isolates with 24-h CFU reductions ranging from −2.62 to −4.67 log10 CFU/ml. The combination of I/R and amikacin exhibited indifferent interactions against all isolates, with combined drugs achieving −0.51- to −3.33-log10 CFU/ml reductions. No resistant subpopulations were observed during I/R and colistin combination studies, and when added to amikacin, I/R prevented the emergence of amikacin resistance. Against these six multidrug-resistant P. aeruginosa, I/R alone achieved significant CFU reductions against I/R-susceptible isolates. Combinations of I/R plus colistin resulted in additivity or synergy against some P. aeruginosa, whereas the addition of amikacin did not provide further antibacterial efficacy against these isolates.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Furong Qiu ◽  
Jian Jiang ◽  
Yueming Ma ◽  
Guangji Wang ◽  
Chenglu Gao ◽  
...  

The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the meanCmaxof midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC0–12,Cmax, andt1/2of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A.


2021 ◽  
Vol 36 (4) ◽  
pp. 662-662
Author(s):  
Ott S ◽  
Gonzalez L ◽  
Redell J ◽  
Duran J ◽  
Schatz P ◽  
...  

Abstract Objective Few studies have addressed serum levels of hypothalamic hormones, as a consequence of sports-related concussion, in concussed, female adolescent athletes. Methods Female athletes, ages 14–18, were assigned to two study groups: 1) 18 diagnosed with a sports-related concussion (SRC) and evaluated within 7 days of injury, and 2) 18 healthy participants matched on age, education, and sport. Participants self-reported menstrual cycle status, with Days 1–15 of the menstrual cycle corresponding to the Follicular phase and days >15 to the Luteal phase. Blood samples were drawn for Plasma concentration measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), adrenocorticotropin hormone (ACTH), prolactin, growth hormone (GH) and progesterone. Using progesterone plasma concentration, <=2 ng/mL corresponding to the Follicular phase and > 2 ng/mL corresponding to the Luteal phase. Results Across both groups, there was agreement between self-reported and progesterone plasma concentrations menstrual cycle Follicular (71.4%) or Luteal phase (52.9%) [X2(1) = 2.33, p = 0.13, phi = 0.25] in identifying menstrual cycle phases. Within the non-concussed controls, there was 90% agreement for Follicular phase and only 33.3% agreement for Luteal phase [X2(1) = 1.55, p = 0.30, phi = 0.29], and for the concussed athletes there was 54.5% agreement for Follicular phase and 75% agreement for Luteal phase [X2(1) = 1.66, p = 0.35, phi = 0.30] Conclusions We provide preliminary evidence of disruption of the hypothalamic–pituitary-axis (HPA) following mTBI as there was a 90% agreement between self-reported follicular phase and follicular phase determined by Progesterone levels for non-concussed females as compared to 54% agreement between the same measures for concussed females.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S284-S285
Author(s):  
Handan Noyan ◽  
Andaç Hamamcı ◽  
Zeynep Fırat ◽  
Ayşegül Sarsılmaz Oygen ◽  
Alp Üçok

Abstract Background The menstrual cycle is a favorable model for examining the influence of ovarian hormones on cognition, emotion and brain functions. Ovarian hormones have substantial effects on task-related brain activity, but their impacts on functional connectivity at rest have been investigated by a few studies conducted with healthy individuals and these pre-existing findings are inconsistent. As for schizophrenia, different influences of ovarian hormones were reported. For instance, the estrogen hypothesis of schizophrenia has suggested that estrogen plays a neuroprotective role in the pathophysiology of this disorder. The present study investigates resting state functional connectivity (RS-FC) alterations related to menstrual cycle phase and/or hormone levels in patients with schizophrenia and healthy controls and aims to contribute to the understanding of the effects of ovarian hormones on the pathogenesis of schizophrenia and brain functions. Methods The study was conducted with 13 women with schizophrenia (the mean of age: 32 ± 7.67) and 13 healthy women (the mean of age: 30.08 ± 7.27). Resting state functional Magnetic Resonance Imaging (fMRI) scanning, as well as hormonal and clinical assessments, were applied to each participant twice, during two menstrual cycle phases: early follicular (Days 2–6; low estrogen/progesterone) and mid-luteal (Days 20–22; high estrogen/progesterone). The serum hormone levels of estradiol, progesterone, prolactin (only in the patients), follicle-stimulating and luteinizing were assessed. The clinical assessment interviews included the Brief Psychiatric Rating Scales, the Clinical Global Impression (only for the patients), the Global Assessment of Functioning and the Calgary Depression Rating Scale for Schizophrenia (for both groups). Results Our findings revealed that no cycle phase-related alterations existed in RS-FC in both groups. However, specific correlations between each hormone and RS-FC were found in both cycle phases for two groups. In the patients, estrogen was positively correlated with the auditory network (AN) connectivity in the left amygdala at the early follicular phase. In the controls, the positive correlations to progesterone were found in the precuneus for the connectivity of the posterior default mode network (DMN) and the left-frontoparietal network (FPN) during the early follicular phase. Also, progesterone was negatively correlated with the executive control network (ECN) connectivity in the right superior frontal gyrus at the mid-luteal phase in the controls. Furthermore, the patients had lower progesterone levels during the mid-luteal phase compared to the controls (p<0.05). The severity of the psychotic symptoms of the patients didn’t change between the cycle phases. Discussion To our knowledge, this is the first study to examine the influence of the menstrual cycle on the brain’s RS-FC in schizophrenia. Our results indicated that the effects of the menstrual cycle on RS-FC were more prominent in the controls rather than the patients with schizophrenia; and that the findings for the patient group may be associated with the additional mechanisms responsible from schizophrenia. This might imply that differentiating the menstrual cycle effects is difficult in a complex disorder such as schizophrenia. The results obtained from the controls are consistent with the previous findings indicating that the menstrual cycle effects might be associated with the connectivity of the DMN and cognition-related networks. Moreover, our results suggested that estrogen might have a modulating effect on the intrinsic functional connectivity changes in the patients, while progesterone, might mediate to that in the controls.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Md. Akil Hossain ◽  
Hae-chul Park ◽  
Kyunghun Jeong ◽  
Yang ho Jang ◽  
Dae Gyun Kim ◽  
...  

The pharmacokinetics of marbofloxacin in pigs after intravenous (i.v.), intramuscular (i.m.), and peroral (p.o.) administration and pharmacokinetic/pharmacodynamic indices of this drug against Korean local isolates ofActinobacillus pleuropneumoniaewere determined in this study. Marbofloxacin (2.50 mg/kg of body weight) was administered, and blood samples were collected with designated time intervals. Plasma-extracted marbofloxacin was injected into the LC-MS/MS system. The in vitro and ex vivo antibacterial activities of marbofloxacin were evaluated against 20 isolates ofA. pleuropneumoniae. The mean peak plasma concentrations (Cmax) after i.v., i.m., and p.o administration were2.60±0.10,2.59±0.12, and2.34±0.12 µg/mL at0.25±0.00,0.44±0.10, and1.58±0.40 h, respectively. The area under the plasma concentration-time curves (AUC0–24) and elimination half-lives were24.80±0.90,25.80±1.40, and23.40±5.00 h·μg/mL and8.60±0.30,12.80±1.10, and8.60±0.00 h, for i.v., i.m., and p.o. administration, correspondingly. The AUC0–24/MICs of marbofloxacin after i.v., i.m., and p.o. administration were253.86±179.91,264.1±187.16, and239.53±169.75 h, respectively. TheCmax/MIC values were26.58±18.84,26.48±18.77, and23.94±16.97, and T>MICs were42.80±1.01,36.40±1.24, and38.60±1.18 h, after i.v., i.m., and p.o. administration, respectively. Thus, marbofloxacin dosage of 2.50 mg/kg of body weight by i.v., i.m., and p.o. administration with 24 h dosing interval will provide effective treatment for the infection of pig byA. pleuropneumonia.


1994 ◽  
Vol 86 (2) ◽  
pp. 227-231 ◽  
Author(s):  
J. D. M. Albano ◽  
S. K. Campbell ◽  
A. Farrer ◽  
J. G. B. Millar

1. Urinary kallikrein excretion was measured in healthy male subjects and in healthy pre- and post-menopausal females. 2. Urinary kallikrein excretion was shown to be constant throughout a 24 h period. Individual male subjects showed little fluctuation in urinary kallikrein excretion; within-subject variance accounted for 1.65% of the total. 3. Female subjects with ovulatory menstrual periods excreted significantly more kallikrein than post-menopausal females and males. 4. Pre-menopausal females showed a much greater within-subject variation in urinary kallikrein excretion and this could be related to the stage of the menstrual cycle, with significantly greater urinary kallikrein excretion in the luteal phase than in the follicular phase. 5. Plasma renin activity and plasma aldosterone concentration also showed a menstrual variation, with concentrations in the luteal phase being significantly higher than those in the follicular phase. 6. The rise in urinary kallikrein excretion in the luteal phase could be abolished by oral administration of the aldosterone antagonist spironolactone. 7. Urinary kallikrein excretion in post-menopausal females was similar to the range found in males, and showed no cyclic changes over a 4 week period. 8. Gender and menstrual status should be taken into account in studies of the physiological role of tissue kallikreins.


2011 ◽  
Vol 55 (3) ◽  
pp. 1194-1198 ◽  
Author(s):  
Rina P. M. Wong ◽  
Sam Salman ◽  
Kenneth F. Ilett ◽  
Peter M. Siba ◽  
Ivo Mueller ◽  
...  

ABSTRACTDesbutyl-lumefantrine (DBL) is a metabolite of lumefantrine. Preliminary data fromPlasmodium falciparumfield isolates show greater antimalarial potency than, and synergy with, the parent compound and synergy with artemisinin. In the present study, thein vitroactivity and interactions of DBL were assessed from tritium-labeled hypoxanthine uptake in cultures of the laboratory-adapted strains 3D7 (chloroquine sensitive) and W2mef (chloroquine resistant). The geometric mean 50% inhibitory concentrations (IC50s) for DBL against 3D7 and W2mef were 9.0 nM (95% confidence interval, 5.7 to 14.4 nM) and 9.5 nM (95% confidence interval, 7.5 to 11.9 nM), respectively, and those for lumefantrine were 65.2 nM (95% confidence interval, 42.3 to 100.8 nM) and 55.5 nM (95% confidence interval, 40.6 to 75.7 nM), respectively. An isobolographic analysis of DBL and lumefantrine combinations showed no interaction in either laboratory-adapted strain but mild synergy between DBL and dihydroartemisinin (sums of the fractional inhibitory concentrations of 0.92 [95% confidence interval, 0.87 to 0.98] and 0.94 [95% confidence interval, 0.90 to 0.99] for 3D7 and W2mef, respectively). Using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry assay and 94 day 7 samples from a previously reported intervention trial, the mean plasma DBL was 31.9 nM (range, 1.3 to 123.1 nM). Mean plasma DBL concentrations were lower in children who failed artemether-lumefantrine treatment than in those with an adequate clinical and parasitological response (ACPR) (P= 0.053 versusP> 0.22 for plasma lumefantrine and the plasma lumefantrine-to-DBL ratio, respectively). DBL is more potent than the parent compound and mildly synergistic with dihydroartemisinin. These properties and the relationship between day 7 plasma concentrations and the ACPR suggest that it could be a useful alternative to lumefantrine as a part of artemisinin combination therapy.


2001 ◽  
Vol 13 (3) ◽  
pp. 151 ◽  
Author(s):  
Takeshige Otoi ◽  
Aya Ooka ◽  
Masako Murakami ◽  
N.W. Kurniani Karja ◽  
Tatsuyuki Suzuki

The present study was conducted to examine the effects of the stage of the oestrous cycle on the meiotic competence of canine oocytes and also to investigate the relationship between the stage of the oestrous cycle and the relative size distribution of oocytes obtained from bitches at three stages of the cycle (anoestrus, follicular phase and dioestrus). Only healthy-looking cumulus–oocyte complexes were used for in vitro maturation and these were divided into three groups based on diameter (<110, 110 to <120 and ≥120 µm). The mean diameter of oocytes from ovaries at anoestrus, the follicular phase and dioestrus was 103.6, 119.2 and 107.7 µm, respectively. The percentage of large oocytes (120 µm) collected at the follicular phase was higher (P<0.01) than that collected at dioestrus and the percentage of oocytes ≥120 µm collected from ovaries at dioestrus was higher (P<0.01) than that collected at anoestrus. After culture for 72 h, significantly more oocytes reached metaphase II (MII) in the follicular phase than in the other stages (P<0.01), and more oocytes reached MII in dioestrus than in anoestrus (P<0.05). In the ≥120 µm group, the frequency of oocytes that resumed meiosis in the follicular phase was higher (P<0.05) than in the other stages. However, in the smaller diameter (<120 µm) groups, there were no significant differences between ovaries at different stages of the oestrous cycle with respect to the proportion of oocytes reaching each stage of meiosis. Thus, the oestrous cycle stage influences maturation frequency. Moreover, oocytes demonstrated a size-related ability to undergo meiotic maturation, irrespective of the stage of the oestrous cycle. These results suggest that the effects of the stage of the oestrous cycle may result from differences in the distribution of large oocytes.


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