Effects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans

1988 ◽  
Vol 119 (4) ◽  
pp. 474-480 ◽  
Author(s):  
Charles Mallo ◽  
Radwan Zaidan ◽  
André Faure ◽  
Jocelyne Brun ◽  
Guy Chazot ◽  
...  

Abstract. An oral preparation of melatonin was administered daily at 22.00 h to 6 healthy volunteers during summer on 4 consecutive days (days 1–4). The daily dose was 8 mg of melatonin as a single. Three 24-h melatonin, cortisol and prolactin profiles were determined in plasma by radioimmunological methods: 1) before treatment (day 0); 2) the first day after the 4-day treatment had been stopped (day 5), 3) the third day after withdrawal of this treatment (day 7). For the melatonin rhythm, an advanced phase was observed at day 7 vs day 0, whereas the amplitude and the mesor were not modified, whatever the day. For the prolactin profile, a significant increase as compared with the control day (day 0) was detected only at day 7 between 19.00 and 21.00 h. No modification was recorded for the plasma cortisol secretion. These results suggest that melatonin, when administered at a high dose over a short period, can influence the endocrine rhythms, and especially its own endogenous secretion. This effect must be investigated over several days after the treatment has ended.

1985 ◽  
Vol 110 (4) ◽  
pp. 546-552 ◽  
Author(s):  
E. Domański ◽  
E. Stupnicka ◽  
F. Przekop ◽  
E. Wolińska-Witort

Abstract. It has previously been observed that sheep subjected to repeated and prolonged stress stimuli showed biphasic cortisol responses. On the first and second day of stimulation an elevation was observed, while on the subsequent days and on the day after the stimulation a marked suppression of plasma cortisol level and a disappearance of its circadian rhythm was noted. It was hypothesized that these changes in the secretion of the hormone were caused by the alteration of catecholaminergic systems in the CNS. To verify this suggestion chemical lesions of the catecholergic systems of the diencephalon were carried out by the infusion of 6-hydroxydopamine (6-OHDA) into the third cerebral ventricle and animals treated in this fashion were subjected to repeated and prolonged electrical mild footshocking (applied during 3 days). The pretreated animals lost the circadian rhythm in cortisol secretion on the days before as well as during and after the electrical stimulation. The animals pretreated with 6-OHDA showed a significant rise of the plasma cortisol level during stimulation. This rise, as the highest daily concentration, occurring within about 1 h after the beginning of footshocking, was significantly accelerated in time with respect to the physiological acrophase, occurring in the early morning hours at the end of prestimulatory days. On the other hand, the pretreated animals did not show the decrease of plasma cortisol levels on the day after the stimulation, observed in normal non-pretreated ones. It is suggested that the absence of the suppression of plasma cortisol concentration in the animals pretreated with 6-OHDA on the day after the stimulation may be due to the blockade of the ventral noradrenergic bundle innervating the medial basal hypothalamus, while disappearance of the circadian rhythm of cortisol secretion was due to the disturbance in the function of retinohypothalamic projection.


VASA ◽  
2010 ◽  
Vol 39 (4) ◽  
pp. 344-348 ◽  
Author(s):  
Jandus ◽  
Bianda ◽  
Alerci ◽  
Gallino ◽  
Marone

A 55-year-old woman was referred because of diffuse pruritic erythematous lesions and an ischemic process of the third finger of her right hand. She was known to have anaemia secondary to hypermenorrhea. She presented six months before admission with a cutaneous infiltration on the left cubital cavity after a paravenous leakage of intravenous iron substitution. She then reported a progressive pruritic erythematous swelling of her left arm and lower extremities and trunk. Skin biopsy of a lesion on the right leg revealed a fibrillar, small-vessel vasculitis containing many eosinophils.Two months later she reported Raynaud symptoms in both hands, with a persistent violaceous coloration of the skin and cold sensation of her third digit of the right hand. A round 1.5 cm well-delimited swelling on the medial site of the left elbow was noted. The third digit of her right hand was cold and of violet colour. Eosinophilia (19 % of total leucocytes) was present. Doppler-duplex arterial examination of the upper extremities showed an occlusion of the cubital artery down to the palmar arcade on the right arm. Selective angiography of the right subclavian and brachial arteries showed diffuse alteration of the blood flow in the cubital artery and hand, with fine collateral circulation in the carpal region. Neither secondary causes of hypereosinophilia nor a myeloproliferative process was found. Considering the skin biopsy results and having excluded other causes of eosinophilia, we assumed the diagnosis of an eosinophilic vasculitis. Treatment with tacrolimus and high dose steroids was started, the latter tapered within 12 months and then stopped, but a dramatic flare-up of the vasculitis with Raynaud phenomenon occurred. A new immunosupressive approach with steroids and methotrexate was then introduced. This case of aggressive eosinophilic vasculitis is difficult to classify into the usual forms of vasculitis and constitutes a therapeutic challenge given the resistance to current immunosuppressive regimens.


Author(s):  
Najat F. Mohammed Salih ◽  
Gazwa D. Al-Nakeeb

This study aimed to compare the histological changes in the neonatal kidney after their mothers exposed to different doses of silver nanoparticles colloidal solution (AgNPs) during the three stages of pregnancy. Pregnant Swiss albino mice (n=60) were randomly divided into three treated groups. They were intraperitoneally injected with AgNPs for 7 days during each stage of the gestational period. The newborn mice were sacrificed immediately after the birth, and the kidneys were being collected for histopathological analysis. The results showed that the AgNPs caused histological changes in the neonatal kidneys; vacuolation of some renal vesicles and cortical tubules, cystic tubular dilation, glomerular tuft shrinkage, and focal tubular necrosis in the first week-dose exposed pregnant. Disintegrating of immature glomeruli, distention of Bowman’s space of mature glomeruli, tubular necrosis, loss of renal parenchyma, medullar tubules containing hyaline casts, and subcapsular haemorrhage in the second week-dose exposed pregnant. Massive hypercellularity in the deeper part of the renal cortex, cortical and medullary tubules dilation, atrophy of subcapsular immature tubules, cortical cyst formation, glomerular tuft necrosis, dilation of Bowman’s space with evidence of crescent formation, and medullar portion replaced by scant loose connective tissue containing few numbers of tubules the third week-dose exposed pregnant. The results showed that the AgNPs has more negative effects on the kidney development at the third week-high dose and comparing the histological changes in the neonatal kidney were appeared in a time-depended manner and in a dosedepended manner. More researches must be carried out to obtain better understanding of AgNPs toxicity on fetal development and its ability as a teratogenic agent to induce external and internal abnormalities in the fetus.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1264.2-1265
Author(s):  
O. Krichevskaya ◽  
T. Dubinina ◽  
E. Ilinykh ◽  
S. Glukhova ◽  
A. Demina

Background:NSAIDs remain the first-line drugs in treatment of AS. During pregnancy, COX-2 non-selective NSAIDs are allowed for intake up to 32 weeks, but the question of the dose-dependent effect of NSAIDs on fetal organogenesis in the 1st trimester and on fetal kidney function and the increased risk of bleeding in childbirth when taken in the second half of pregnancy continues to be discussed. At the same time, data on the effectiveness of NSAIDs, including their low and medium doses, during pregnancy are extremely small.Objectives:to describe the frequency of using NSAIDs during pregnancy, to determine relationship between the dose of NSAIDs, adherence to therapy with the activity of AS.Methods:50 pregnancies were followed in 49 pregnant women with confirmed AS (modified New York criteria, 1984). The average age of the pts was 31.6 ± 4.9 years, the duration of the disease was 134.4 ± 85.8 months. The visits were conducted at 10-11, 20-21, and 31-32 weeks of pregnancy. The BASDAI in the month of conception and in the trimesters (trim.) of pregnancy was: 1,4[0,6; 3,3]; 2,3[1,2; 4,4]; 2,8[1,4; 4,2] and 2,2[1,6; 4,0], respectively. The level of nocturnal back pain according to the NRS in the first, second and third trim. was: 3.2±2.0; 5.4±2.5 and 5.2±2.6, respectively. The drug of choice was ibuprofen at a maximum daily dose of 1200 mg, its withdrawal - no later than 32 weeks of pregnancy.Adherence to NSAID therapy was defined as the ratio of the actual dose taken to the prescribed dose; an indicator of less than 80% was regarded as non-adherence to therapy. The total dose of NSAIDs was determined by the NSAID intake index (M. Dougados, 2001). The” actual daily dose” of ibuprofen was the sum of the doses of ibuprofen taken, divided by the number of actual days of taking the drug. The “average daily dose” was defined as the sum of the ibuprofen doses taken, divided by the number of days in the trimester.Results:At the time of conception and in the first, second and third trim. of pregnancy, NSAIDs were taken 23 (46%), 20 (40%), 30 (60%) and 21 (43.8%) women, respectively. The NSAID intake index, the actual and average daily dose of ibuprofen are shown in the Table 1.month of conceptiontrim. 1trim. 2trim. 3the actual daily dose, mg-700[425; 800]800[400; 1000]750[400; 1200]the average daily dose, mg-158[87,9; 307,7]355,1[138,5; 685,7]580[320; 1200]NSAIDs intake index28,6 [16,7; 50]5,8 [2,9; 11,8]15,5 [4,7; 30,9]24,4 [9,5; 50]The index of NSAID intake in the first trim. was lower than before pregnancy and in the second half of gestation (p<0.05 compared to the month of conception, II and III trim.). The average daily dose of ibuprofen was also lower in the first trim. than in the second and third trim. (p<0.05), while the actual daily dose in the second trim. was higher than in the first and third trim. (p<0.05 in all cases).There was no correlation between BASDAI AS activity, the level of nocturnal pain and the ibuprofen intake index, likewise the fact of NSAID withdrawal throughout pregnancy. In addition, there were no differences in BASDAI levels and back pain in women with a subjective need for NSAIDs, who did and did’t take ibuprofen.50% of women were committed to NSAID therapy in the first trim., 43.5% in the second trim., and 67.4% in the third trim. In pts with non-adherence to NSAID therapy, the BASDAI level was higher than in those who followed the recommendations of the rheumatologist throughout pregnancy: in the first trim. – 3.8[3.4; 4.7] and 1.7[0.8; 2.2]; in the second trim. - 3[2.3; 4.6] and 1.4[0.8; 2.7]; in the third trim. - 3.1[2.1; 4.0] and 1.7[1.1; 4.0], p<0.05 in all cases. However, women with adherence > 80% were initially less active and NSAIDs were prescribed “on demand”, which increased their compliance.Conclusion:intake of ibuprofen in low doses does not affect the activity of AS. Due to the ongoing discussion about the effect of NSAIDs on neonatal outcomes, further international studies are required for development an optimal treatment regimen during pregnancy with a possible extension of the indications for the appointment of TNF inhibitors (BASDAI<4).Disclosure of Interests:None declared.


2020 ◽  
Vol 499 (3) ◽  
pp. 3738-3748
Author(s):  
R H Østensen ◽  
C S Jeffery ◽  
H Saio ◽  
J J Hermes ◽  
J H Telting ◽  
...  

ABSTRACT The Kepler spacecraft observed the hot subdwarf star PHL 417 during its extended K2 mission, and the high-precision photometric light curve reveals the presence of 17 pulsation modes with periods between 38 and 105 min. From follow-up ground-based spectroscopy, we find that the object has a relatively high temperature of 35 600 K, a surface gravity of $\log g / {\rm cm\, s^{-2}}\, =\, 5.75$ and a supersolar helium abundance. Remarkably, it also shows strong zirconium lines corresponding to an apparent +3.9 dex overabundance compared with the Sun. These properties clearly identify this object as the third member of the rare group of pulsating heavy-metal stars, the V366-Aquarii pulsators. These stars are intriguing in that the pulsations are inconsistent with the standard models for pulsations in hot subdwarfs, which predicts that they should display short-period pulsations rather than the observed longer periods. We perform a stability analysis of the pulsation modes based on data from two campaigns with K2. The highest amplitude mode is found to be stable with a period drift, $\dot{P}$, of less than 1.1 × 10−9 s s−1. This result rules out pulsations driven during the rapid stages of helium flash ignition.


1988 ◽  
Vol 97 (4) ◽  
pp. 376-380 ◽  
Author(s):  
Bruce N. Benjamin ◽  
Henley Harrison ◽  
Paul A. Gatenby ◽  
Kaye Cameron ◽  
Robert Kitchen ◽  
...  

Ten patients received lymphoblastoid alpha-interferon (Wellferon) in a crossover study so that Wellferon and standard microsurgical laryngeal laser therapy could be compared to laser therapy alone. Wellferon was administered initially at an intravenous high dose of 15 megaunits/m2 for 5 days followed by a daily dose of 2 megaunits/m2 subcutaneously for 6 months. Dosage was adjusted according to predefined toxicity. One patient was withdrawn from the study. Of the others, all but one received over 75 % of the planned total dose. At follow-up of the nine assessable patients, complete remission was achieved in two of them, partial remission in four, and no response in the remainder. The two complete remissions were sustained for 2 years, but the four partial remissions were not sustained. Thus, a role for alpha-interferon in the kind of regimen used here remains to be established.


2000 ◽  
Vol 34 (5) ◽  
pp. 619-621 ◽  
Author(s):  
Jessica L Goren ◽  
Gary M Levin

OBJECTIVE: To report a case in which bipolar depression was resistant to usual therapies, requiring dosages of bupropion >450 mg/d and to review the literature on mania associated with bupropion and propose a potential theory of a dose-related threshold associated with bupropion and mania. CASE SUMMARY: A 44-year-old white man with a 25-year history of bipolar affective disorder presented with depression resistant to usual therapies. Bupropion therapy was initiated and the dosage was titrated to 600 mg/d. After exceeding the maximum recommended daily dose (450 mg/d), he experienced a manic episode attrib uted to high-dose bupropion. DISCUSSION: Due to increased risk of seizures, current prescribing guidelines state that the total daily dose of bupropion is not to exceed 450 mg/d. Since bupropion is the agent least likely to cause a manic switch in bipolar disorder, this agent seemed a logical choice to treat the patient's depression. Due to a lack of response, the bupropion dosage was titrated to a maximum of 600 mg/d. Since the patient did not switch into mania until the dosage exceeded 450 mg/d, we speculate that this adverse reaction is a dose-related phenomenon. Scientific literature supports this theory. CONCLUSIONS: A switch into mania is a potential risk associated with antidepressant drug use in bipolar affective disorder. Bupropion is believed to be associated with a decreased risk compared with other antidepressant therapies. However, our case report as well as others support the theory that this decreased risk may be due to dosages not exceeding the recommended daily dose (450 mg/d). Doses of bupropion >450 mg/d should be used with caution in depressed patients with bipolar affective disorder.


2003 ◽  
Vol 47 (3) ◽  
pp. 1072-1080 ◽  
Author(s):  
Spotswood L. Spruance ◽  
Terry M. Jones ◽  
Mark M. Blatter ◽  
Mauricio Vargas-Cortes ◽  
Judy Barber ◽  
...  

ABSTRACT Oral valacyclovir is better absorbed than oral acyclovir, increasing acyclovir bioavailability three- to fivefold. This provides the opportunity to explore whether high systemic acyclovir concentrations are effective in the treatment of cold sores (herpes labialis). Two randomized, double-blind, placebo-controlled studies were conducted. Subjects were provided with 2 g of valacyclovir twice daily for 1 day (1-day treatment), 2 g of valacyclovir twice daily for 1 day and then 1 g of valacyclovir twice daily for 1 day (2-day treatment), or a matching placebo and instructed to initiate treatment upon the first symptoms of a cold sore. In study 1, the median duration of the episode (primary endpoint) was reduced by 1.0 day (P = 0.001) with 1-day treatment and 0.5 days (P = 0.009) with 2-day treatment compared to placebo. Similarly, the mean duration of the episode was statistically significantly reduced by 1.1 days with 1-day treatment and 0.7 days with 2-day treatment compared to placebo. The proportion of subjects in whom cold sore lesion development was prevented and/or blocked was increased by 6.4% (P = 0.096) with 1-day treatment and 8.5% (P = 0.061) with 2-day treatment compared to placebo. The time to lesion healing and time to cessation of pain and/or discomfort were statistically significantly reduced with valacyclovir compared to placebo. In study 2, results similar to those in study 1 were obtained. AEs were similar across treatment groups. These studies provide evidence supporting a simple, 1-day valacyclovir treatment regimen for cold sores that is safe and effective. The 1-day valacyclovir regimen offers patients a unique and convenient dosing alternative compared to available topical therapies.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Hamid Ullah Wani ◽  
Saad Al Kaabi ◽  
Manik Sharma ◽  
Rajvir Singh ◽  
Anil John ◽  
...  

Background. Lamivudine is the most affordable drug used for chronic hepatitis B and has a high safety profile. With the daily dose of 100 mg there is progressive appearance of resistance to lamivudine therapy. In our study we used 150 mg of lamivudine daily as a standard dose which warrants further exploration for the efficacy of the drug. Aims of the Study. To assess the efficacy of lamivudine 150 mg daily on resistance in patients with chronic hepatitis B. Methods. This retrospective study consists of 53 patients with chronic hepatitis B treated with 150 mg of lamivudine daily. The biochemical and virological response to the treatment were recorded at a 1-year and 2-, 3-, 4-, and 5-year period and time of emergence of resistance to the treatment was noted. Results. The mean age of the patients was 54 years with 80% being males. The resistance to lamivudine 150 mg daily at 1 year and 2, 3, and 5 years was 12.5%, 22.5%, 37.5%, and 60%, respectively, which is much less compared to the standard dose of 100 mg of lamivudine. Conclusions. Lamivudine is safe and a higher dose of 150 mg daily delays the resistance in patients with chronic hepatitis B.


Author(s):  
Roy Gomel ◽  
Simchon Faigler ◽  
Tsevi Mazeh ◽  
Michał Pawlak

Abstract This is the third of a series of papers that presents an algorithm to search for close binaries with massive, possibly compact, unseen secondaries. The detection of such a binary is based on identifying a star that displays a large ellipsoidal periodic modulation, induced by tidal interaction with its companion. In the second paper of the series we presented a simple approach to derive a robust modified minimum mass ratio (mMMR), based on the observed ellipsoidal amplitude, without knowing the primary mass and radius, assuming the primary fills its Roche lobe. The newly defined mMMR is always smaller than the actual mass ratio. Therefore, a binary with an mMMR larger than unity is a good candidate for having a massive secondary, which might be a black hole or a neutron star. This paper considers 10,956 OGLE short-period ellipsoidals observed towards the Galactic Bulge. We re-analyse their modulation and identify 136 main-sequence systems with mMMR significantly larger than unity as candidates for having compact-object secondaries, assuming their observed periodic modulations reflect indeed the ellipsoidal effect. Obviously, one needs follow-up observations to find out the true nature of these companions.


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