scholarly journals Bioavailability and Sustained Plasma Concentrations of CoQ10 in Healthy Volunteers by a Novel Oral Timed-Release Preparation

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 527 ◽  
Author(s):  
Alessio Martucci ◽  
Delia Reurean-Pintilei ◽  
Anamaria Manole
Keyword(s):  
Single Dose ◽  
Coenzyme Q10 ◽  
Plasma Concentrations ◽  
Antioxidant Properties ◽  
Sharp Decrease ◽  
Continuous Administration ◽  
Blood Concentrations ◽  
Mean Values ◽  
High Concentrations ◽  
Group B

Coenzyme Q10 (CoQ10) is a natural compound with potent antioxidant properties. Its provision through diet does not always allow adequate levels in the human body, and supplementation is often necessary. This bioavailability study intended to explore the plasma concentration levels of a novel CoQ10 oral preparation (COQUN®, Coenzyme Q10 Miniactives Retard 100 mg capsules) mimicking assumption on a regular basis. Twenty-four healthy adults tested a single dose of CoQ10 100 mg in one day to assess bioavailability. After a one week wash-out period, they were randomly assigned (1:1) to continuous administration for four weeks: Group A (n = 12) 100 mg once a day (OD); and Group B (n = 12) 100 mg twice a day (BID). During the single dose phase, Cmax was observed at 4 h, and the mean values of AUCt and Tmax were 8754 μg/mL·h and 4.29 h, respectively. The multiple dose phase showed increasing plasma levels up to 7 days after the start of administration, and sustained high concentrations during the all administration period. No relevant adverse events were reported. These results show that Miniactives® technology can release CoQ10 to allow high constant blood concentrations without a sharp decrease. This may be the first step of evidence for a potential new antioxidative treatment in human chronic diseases deserving high CoQ10 levels.

scholarly journals Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population

1998 ◽  
Vol 44 (6) ◽  
pp. 1334-1338 ◽  
Author(s):  
Douglas Stickle ◽  
Barbara Cole ◽  
Karl Hock ◽  
Keith A Hruska ◽  
Mitchell G Scott
Keyword(s):  
Correlation Coefficient ◽  
Cystatin C ◽  
Linear Correlation ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Inulin Clearance ◽  
Blood Concentrations ◽  
Group A ◽  
Group B

Abstract Measurement of blood concentrations of cystatin C (cysC), a cysteine protease inhibitor present in human plasma, has been suggested for use as an indicator of glomerular filtration rate (GFR) in a manner analogous to the use of plasma creatinine (SCR). In this study, cysC and SCR were measured in plasma from pediatric patients (4–19 years) with renal disease for whom a “gold standard” measurement of GFR via inulin clearance (CIN) was available. The data analyses were divided into two age groups: group A (4–12 years, n = 26) and group B (12–19 years, n = 34). For both age groups, the linear correlation coefficient of [cysC]−1 vs CIN (mL/min/1.73 m2) (r = 0.765 for group A and r = 0.869 for group B) was less than that of the linear correlation coefficient of [SCR]−1 vs CIN (r = 0.841 for group A and r = 0.892 for group B). As a single measurement for detection of abnormal GFR, however, the optimum receiver-operator characteristic point for cysC measurement (for group A at cysC >1.2 mg/L, sensitivity = 80%, specificity = 91%; and for group B at cysC >1.4 mg/L, sensitivity = 87%, specificity = 100%) was numerically superior to that for SCR measurement (for group A at SCR >8.0 mg/L, sensitivity = 67%, specificity = 100%; and for group B at SCR >9.0 mg/L, sensitivity = 91%, specificity = 91%), using a reference value for normal GFR of CIN > 90 mL/min/1.73 m2. However, these differences were not statistically significant. CysC measurement appears to be broadly equivalent to SCR measurement for estimation of GFR in pediatric patients.

scholarly journals Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies

2017 ◽  
Vol 31 (5) ◽  
pp. 589-598 ◽  
Author(s):  
Kim PC Kuypers ◽  
Patrick C Dolder ◽  
Johannes G Ramaekers ◽  
Matthias E Liechti
Keyword(s):  
Single Dose ◽  
Drug Use ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Cognitive Empathy ◽  
Reactivity Index ◽  
Emotional Empathy ◽  
Blood Concentrations ◽  
Trait Empathy ◽  
Moderating Role

Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.

CHANGES IN CONCENTRATIONS OF FOLLICLE-STIMULATING HORMONE, LUTEINIZING HORMONE, PROLACTIN AND PROGESTERONE IN THE PLASMA OF EWES DURING THE TRANSITION FROM ANOESTRUS TO BREEDING ACTIVITY

1977 ◽  
Vol 75 (1) ◽  
pp. 127-136 ◽  
Author(s):  
J. S. WALTON ◽  
JUDITH R. McNEILLY ◽  
A. S. McNEILLY ◽  
F. J. CUNNINGHAM
Keyword(s):  
Follicle Stimulating Hormone ◽  
Plasma Concentrations ◽  
Cyclic Activity ◽  
Plasma Progesterone ◽  
Progesterone Secretion ◽  
Group A ◽  
High Concentrations ◽  
Group B ◽  
Short Days

The plasma concentrations of FSH, LH, prolactin and progesterone were measured throughout anoestrus and during the resumption of cyclic activity in two groups of ewes. Group A was maintained under conditions of natural daylength throughout the experiment, whereas Group B was exposed to 6 h of light and 18 h of darkness, the change being made abruptly on the longest day. In those ewes kept on short days, oestrus and ovulation occurred 18·3 days (P < 0·05) and 23·4 days (P < 0·001) earlier than in the ewes under conditions of natural daylength. Ovulation preceded oestrus by 18·6 days and 23·1 days in Groups A and B respectively. The occurrence of ovulation was detected by the determination of plasma progesterone concentrations. In all ewes, progesterone levels were basal until the first ovulation when the pattern of secretion was typical of that seen during the oestrous cycle. In the 4 days before ovulation, the plasma progesterone concentration increased slowly to reach a maximum of 0·66 ± 0·12 (s.e.m.) ng/ml on day − 1. The first ovulation was associated with a substantial surge of LH. Similar release of LH, thought to be related to the increased progesterone secretion, was also observed on day −5. Sporadic release of LH was also found before this time in some animals. Plasma concentrations of FSH fluctuated randomly throughout anoestrus and during the transition to established oestrous cycles. These changes were not apparently related to ovulation. Throughout anoestrus, prolactin concentrations were raised but always declined before the time of ovulation. The fall in prolactin concentrations occurred sooner in the ewes on short days, pointing to a relationship with the decreased daylength. These data suggest that the return to oestrous cycles may be brought about by the removal of an antigonadotrophic effect exerted by high concentrations of prolactin in the blood during anoestrus.

LH pattern in ovariectomised rats after continuous blood withdrawal: effects of different substitutions

1982 ◽  
Vol 99 (1) ◽  
pp. 39-43
Author(s):  
H. Th. Schneider ◽  
K. Kraft ◽  
H. Breuer
Keyword(s):  
Plasma Concentrations ◽  
Nacl Solution ◽  
Volume Depletion ◽  
Sodium Potassium ◽  
Mean Values ◽  
Blood Withdrawal ◽  
Group A ◽  
Group B ◽  
Group D ◽  
Ovariectomised Rats

Abstract. Plasma concentrations of LH and of sodium, potassium, total protein and haemoglobin were measured in ovariectomised rats during continuous blood withdrawal up to 180 min; 0.45 ml blood samples were taken every 10 min, the total volume of blood removed not exceeding 9 ml. Four groups of animals were studied: group A received no substitution (controls), group B was substituted with 0.9% NaCl-solution, group C with 3.5% polypeptide solution (Haemaccel), and group D with a suspension of washed erythrocytes from the blood removed. During blood withdrawal, the mean values of LH concentrations as well as the amplitudes of the rhythmic LH pulses remained constant in all the animals. However, the rate of pulses was reduced in the control animals and in the group receiving 0.9% NaCl-solution during the period between 90 and 180 min; in contrast no change was observed in the groups C and D during the whole period. The results presented here show that the characteristic LH pattern in ovariectomised rats is not affected by volume depletion, provided the blood is replaced by a solution containing either a polypeptide or a suspension of washed erythrocytes.

Effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area on the secretion of prolactin and β-endorphin in rams

1992 ◽  
Vol 134 (3) ◽  
pp. 437-448 ◽  
Author(s):  
G. A. Lincoln ◽  
K.-I. Maeda
Keyword(s):  
Body Weight ◽  
Preoptic Area ◽  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Early Summer ◽  
Mediobasal Hypothalamus ◽  
Continuous Administration ◽  
Blood Concentrations ◽  
Micro Implants ◽  
Short Days

ABSTRACT In a previous study, we showed that the local administration of melatonin into the mediobasal hypothalamus (MBH), but not the preoptic area (POA), caused a premature increase in the secretion of FSH and growth of the testes in sexually inactive Soay rams exposed to long days. To extend these observations, we have now measured blood concentrations of prolactin and β-endorphin and the associated peripheral responses in the same animals, to establish whether the treatments produced multiple endocrine changes such as those which occur following exposure to short days. Groups of rams were initially exposed to alternating 16 weekly periods of long days (16 h light: 8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal cycles in the secretion of the pituitary hormones. The treatments were started at 10 weeks under long days, when the animals had a physiology characteristic of the early summer with high blood plasma concentrations of prolactin (associated with growth of the summer pelage), and low concentrations of β-endorphin (associated with low body weight). The animals were assigned at random to the following treatments: (i) micro-implants of melatonin in the MBH, (ii) microimplants of melatonin in the POA, (iii) empty implants in the MBH or POA to act as operated controls, and (iv) no surgery to act as unoperated controls (n=12 rams/treatment). The micro-implants consisted of 22-gauge stainless-steel needles with melatonin fused inside the tip. The implants were inserted bilaterally in the brain, and left in place for 12–14 weeks. The observations continued for a total of 28 weeks while the animals remained under long days. The administration of melatonin in the MBH induced a rapid decrease in plasma concentrations of prolactin while in the POA it induced a less marked but significant effect. The mean times to minimum concentrations of prolactin were 7·4±0·4, 17·3±2·8 and 26·0 ±0·3 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P<0·001, POA vs control P<0·01. In the MBH group, the concentrations of prolactin subsequently increased to a maximum 6 weeks after the end of melatonin treatment. The changes in prolactin were accompanied by changes in growth and moulting of the pelage; only animals in the MBH group showed a conspicuous moult associated with the change from low to high prolactin secretion. There was also a marked effect of melatonin when given into the MBH, but not the POA, on plasma concentrations of β-endorphin, which was correlated with differences between groups in the cycle in body weight. In conclusion, continuous administration of melatonin into the MBH acts like a long-duration melatonin signal and induces a full sequence of biological responses normally evoked by transfer to short days. This is used as evidence that melatonin acts within or close to the MBH to induce the multiple effects of photoperiod in the ram. Journal of Endocrinology (1992) 134, 437–448

Reduction of Isoflurane Minimal Alveolar Concentration by Remifentanil

1996 ◽  
Vol 85 (4) ◽  
pp. 721-728 ◽  
Author(s):  
E. Lang ◽  
A. Kapila ◽  
D. Shlugman ◽  
J. F. Hoke ◽  
P. S. Sebel ◽  
...  
Keyword(s):  
Whole Blood ◽  
Plasma Concentrations ◽  
Skin Incision ◽  
Computer Assisted ◽  
Minimal Alveolar Concentration ◽  
Blood Concentrations ◽  
Isoflurane Concentration ◽  
Arterial Blood ◽  
Opioid Receptor Agonist ◽  
High Concentrations

Background Remifentanil is a new micro-specific opioid receptor agonist currently under investigation. The interaction between opioids and volatile anesthetics is complex. Defining this interaction provides a basis for more rational dosing schemes when such combinations are used for anesthesia and allows the anesthetic potency of remifentanil relative to other opioids to be determined. Methods Two centers enrolled a total of 220 patients. Patients were randomized to receive a target concentration of remifentanil via a computer-assisted continuous infusion device of either 0.0, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 16.0, and 32.0 ng/ml initiated before the administration of isoflurane. Patients were also stratified by groups 18-30, 31-55, and 56-65 yr. After induction of anesthesia with isoflurane the initial patient in each dose group was assigned an age-adjusted isoflurane concentration. The isoflurane concentration for each subsequent patient was adjusted according to the up/down technique until a minimum of 12 patients were enrolled in each group. Arterial blood samples for remifentanil whole blood concentrations were obtained. The patient was observed for purposeful movement for up to 1 min after skin incision. The minimum alveolar concentration (MAC) of isoflurane (0 ng/ml remifentanil group) and MAC reduction of isoflurane by remifentanil were determined. Results The MAC of isoflurane alone was 1.3%. Remifentanil caused an exponential reduction in the MAC of isoflurane with 1.37 ng/ml remifentanil a 77% reduction and 32 ng/ml a 91% reduction of isoflurane MAC. Conclusion The MAC reduction of isoflurane by remifentanil is similar to that produced by other opioids. Although remifentanil was given at extremely high concentrations in the absence of isoflurane, it did not provide adequate anesthesia. A 50% isoflurane MAC reduction is produced by 1.37 ng/ml remifentanil whole blood concentration compared to previously published plasma concentrations of fentanyl of 1.67 ng/ml or sufentanil of 0.14 ng/ml.

Comparative Study of effectiveness of mobilization with movement (MWM) and End range mobilization (ERM) techniques in frozen shoulder

2018 ◽  
Vol 4 (4) ◽  
pp. 519-522
Author(s):  
Jeyakumar S ◽  
Jagatheesan Alagesan ◽  
T.S. Muthukumar
Keyword(s):  
Range Of Motion ◽  
Frozen Shoulder ◽  
Type I ◽  
Mean Values ◽  
Functional Activities ◽  
Group A ◽  
The Mean ◽  
Group B

Background: Frozen shoulder is disorder of the connective tissue that limits the normal Range of motion of the shoulder in diabetes, frozen shoulder is thought to be caused by changes to the collagen in the shoulder joint as a result of long term Hypoglycemia. Mobilization is a therapeutic movement of the joint. The goal is to restore normal joint motion and rhythm. The use of mobilization with movement for peripheral joints was developed by mulligan. This technique combines a sustained application of manual technique “gliding” force to the joint with concurrent physiologic motion of joint, either actively or passively. This study aims to find out the effects of mobilization with movement and end range mobilization in frozen shoulder in Type I diabetics. Materials and Methods: 30 subjects both male and female, suffering with shoulder pain and clinically diagnosed with frozen shoulder was recruited for the study and divided into two groups with 15 patients each based on convenient sampling method. Group A patients received mobilization with movement and Group B patients received end range mobilization for three weeks. The outcome measurements were SPADI, Functional hand to back scale, abduction range of motion using goniometer and VAS. Results: The mean values of all parameters showed significant differences in group A as compared to group B in terms of decreased pain, increased abduction range and other outcome measures. Conclusion: Based on the results it has been concluded that treating the type 1 diabetic patient with frozen shoulder, mobilization with movement exercise shows better results than end range mobilization in reducing pain and increase functional activities and mobility in frozen shoulder.

Studies of the oestrous cycle, oestrus and pregnancy in the koala (Phascolarctos cinereus)

Reproduction ◽  
2000 ◽  
pp. 49-57 ◽  
Author(s):  
SD Johnston ◽  
MR McGowan ◽  
P O'Callaghan ◽  
R Cox ◽  
V Nicolson
Keyword(s):  
Luteal Phase ◽  
Post Partum ◽  
Plasma Concentrations ◽  
External Genitalia ◽  
Oestrous Cycle ◽  
Phascolarctos Cinereus ◽  
Pregnant Females ◽  
Peripheral Plasma ◽  
The Mean ◽  
High Concentrations

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.

Pharmacokinetics and Safety Assessment of Anti-HIV Dapivirine Vaginal Microbicide Rings with Multiple Dosing

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Ex Vivo ◽  
Oral Treatment ◽  
Plasma Concentrations ◽  
Vaginal Ring ◽  
Vaginal Fluid ◽  
Cervical Tissue ◽  
Double Blind ◽  
Group A ◽  
Group B ◽  
Anti Hiv

Objectives: Self-administered vaginal rings are a promising method for delivery of topical anti-HIV microbicidesand might offer an adherence advantage over daily or coitally-dependent dosage forms such as gels. This trialassessed the safety and pharmacokinetic aspects of the Dapivirine Vaginal Ring-004 when worn as multiple rings oversequential periods of ring use by healthy, sexually-active, HIV-negative women.Methods: This double-blind trial was conducted among 48 women (18-40 years). Participants were randomlyassigned to two groups (A or B) and received (3:1) either the dapivirine or a placebo vaginal ring. Group A used tworings over a 56-day period and Group B used three rings over a 57-day period. Safety evaluations were conductedthroughout the trial. Dapivirine concentrations were measured in plasma, vaginal fluid and cervical tissue samplescollected during and after the 56 days (Group A) or 57 days (Group B) of vaginal ring use.Results: Ring-004 was safe and well tolerated in all participants. The pharmacokinetic profile demonstrated arapid increase in plasma and vaginal fluid concentrations and achieved concentrations in vaginal fluids and cervicaltissue well above the in vitro IC99 in cervical tissue (3.3 ng/mL) that were sustained for a 28 to 35-day ring use period(approximately 3000 times higher in vaginal fluids and 14 -1000 times higher in cervical tissue). Drug levels wereassociated with significant inhibitory activity of genital secretions against HIV ex vivo, a biomarker of pharmacodynamics.Individual plasma dapivirine concentrations did not exceed 553 pg/mL and were well below plasma concentrations atthe maximum tolerated dose for oral treatment (mean Cmax 2286 ng/mL).Conclusions: The consecutive use of several rings over a period of up to 57 days was safe and well tolerated, andPK data indicate that a single Ring-004 is likely to be protective for at least 35 days.

scholarly journals Preliminary Study on Pasta Samples Characterized in Antioxidant Compounds and Their Biological Activity on Kidney Cells

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1131 ◽  
Author(s):  
Federico Di Marco ◽  
Francesco Trevisani ◽  
Pamela Vignolini ◽  
Silvia Urciuoli ◽  
Andrea Salonia ◽  
...  
Keyword(s):  
Indoleacetic Acid ◽  
Antioxidant Properties ◽  
Antioxidant Compounds ◽  
Kidney Cells ◽  
Hek 293 ◽  
293 Cells ◽  
High Concentrations ◽  
Β Carotene ◽  
Egg Pasta

Pasta is one of the basic foods of the Mediterranean diet and for this reason it was chosen for this study to evaluate its antioxidant properties. Three types of pasta were selected: buckwheat, rye and egg pasta. Qualitative–quantitative characterization analyses were carried out by HPLC-DAD to identify antioxidant compounds. The data showed the presence of carotenoids such as lutein and polyphenols such as indoleacetic acid, (carotenoids from 0.08 to 0.16 mg/100 g, polyphenols from 3.7 to 7.4 mg/100 g). To assess the effect of the detected metabolites, in vitro experimentation was carried out on kidney cells models: HEK-293 and MDCK. Standards of β-carotene, indoleacetic acid and caffeic acid, hydroalcoholic and carotenoid-enriched extracts from samples of pasta were tested in presence of antioxidant agent to determine viability variations. β-carotene and indoleacetic acid standards exerted a protective effect on HEK-293 cells while no effect was detected on MDCK. The concentrations tested are likely in the range of those reached in body after the consumption of a standard pasta meal. Carotenoid-enriched extracts and hydroalcoholic extracts showed different effects, observing rescues for rye pasta hydroalcoholic extract and buckwheat pasta carotenoid-enriched extract, while egg pasta showed milder dose depending effects assuming pro-oxidant behavior at high concentrations. The preliminary results suggest behaviors to be traced back to the whole phytocomplexes respect to single molecules and need further investigations.

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