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.

scholarly journals The Effect of Grapefruit Juice on the Pharmacokinetics of Tadalafil in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Xiuwei Shen ◽  
Fan Chen ◽  
Fengwei Wang ◽  
Peng Huang ◽  
Wenchao Luo
Keyword(s):  
Grapefruit Juice ◽  
Plasma Concentrations ◽  
Alkaline Condition ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Column Temperature ◽  
Group A ◽  
Group B ◽  
Experimental Group

We developed and validated a novel, sensitive, selective, and inexpensive high-performance liquid chromatography (HPLC) method for the determination of tadalafil in rats plasma and to investigate the effect of grapefruit juice on the pharmacokinetics of tadalafil in rats. The ZORBAX Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) chromatography column can be used to separate tadalafil and carbamazepine (internal standard, IS). A mixture of acetonitrile-0.2% trifluoroacetic acid-water (48 : 10 : 42, V/V/V) was used as the mobile phase with a flow rate of 1.0 mL/min. The column temperature was set at 35.0°C. The detection wavelength was set at 286 nm. The tadalafil was extracted by ethyl acetate from plasma at the alkaline condition. 12 healthy male Sprague-Dawley (SD) rats were randomly divided into two groups, Group A (experimental group, received grapefruit juice 5 mL/kg for 7 days) and Group B (control group, received normal saline for 7 days). All the rats were given a single dose of tadalafil (5 mg/kg) after the last administration. The main pharmacokinetic parameters were calculated by DAS 2.0 software. Under the conditions of this experiment, the plasma concentrations of tadalafil in the range of 10–2000 ng/ml had a good linear relationship. The intra- and interday precision for tadalafil in plasma were less than 15%, and the relative recovery rate was good at low, medium, and high QC levels. The Cmax of tadalafil in the control group and the experimental group was (725.89 ± 161.59) ng/mL and (1271.60 ± 179.31) ng/mL, t1/2 was (9.28 ± 2.07) h and (11.70 ± 1.47) h, AUC (0-t) was (7399.61 ± 696.85) ng·h/mL and (9586.52 ± 2048.81) ng·h/mL, and AUC(0-∞) was (7995.50 ± 707.23) ng·h/mL and (10639.43 ± 2235.94) ng·h/mL, respectively. Results show that the Cmax of tadalafil in group A was 75.17% higher than that in group B, the Vz/F was also reduced, and the t1/2 was increased by 2.42 h. The developed HPLC–DAD method for the determination of tadalafil in rats plasma was accurate, reproducible, specific, and it was found to be suitable for the pharmacokinetics of tadalafil and food-drug interactions. Grapefruit juice can inhibit the metabolism of tadalafil and increase the exposure of tadalafil in rats.

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 Hematological Features in Sheep with IgG and IgM Antibodies against Borrelia burgdorferi sensu lato

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 164
Author(s):  
Labrini V. Athanasiou ◽  
Victoria M. Spanou ◽  
Eleni G. Katsogiannou ◽  
Panagiotis D. Katsoulos
Keyword(s):  
Borrelia Burgdorferi ◽  
Rural Areas ◽  
Blood Analysis ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Igm Antibodies ◽  
Group A ◽  
Group B ◽  
Group D ◽  
Immunofluorescence Antibody

Exposure of sheep to Borreliaburgdorferi sensulato (s.I.) complex, the causative agent of Lyme borreliosis (LB), has been reported in tick-abundant areas worldwide, while no data have been reported in Greece. The aim of the study was to identify the hematological alterations in sheep with seropositivity against Borrelia burgdorferi (s.I.). Blood samples were obtained from 318 tick infested sheep for blood analysis and serological determination of IgG and IgM antibodies against B. burgdorferi by indirect immunofluorescence antibody (IFA) assay after exclusion of endo-ectoparasites and other tick-borne infections. A total number of 162 sheep met the inclusion criteria, allocated in four groups based on the presence or absence of IgG and/or IgM; sheep found negative for IgM and IgG (Group A), positive for IgM (Group B), positive for both IgM and IgG (Group C) and positive for IgG (Group D). Anemia, thrombocytopenia and normal or decreased leukocyte count, mainly due to lymphopenia were the main hematological features observed in seropositive sheep. The presence of these features raises the suspicion of Borrelia infection in tick infested sheep. The seropositivity of 23.58% in sheep raises concerns of Borrelia circulation, especially in rural areas and potential risk of transmission to humans.

scholarly journals Clinical Efficacy Of Ceftriaxone Versus Ciprofloxacin In Paediatric Enteric Fever

2018 ◽  
Vol 08 (02) ◽  
pp. 67-71
Author(s):  
Anila Farhat ◽  
Asma Shaukat ◽  
Tariq Mahmood Khan
Keyword(s):  
Enteric Fever ◽  
Research Study ◽  
Controlled Trial ◽  
Clinical Effectiveness ◽  
Randomized Controlled ◽  
Group A ◽  
The Mean ◽  
Group B ◽  
Objective Determination

Objective: Determination of the clinical effectiveness of ciprofloxacin versus ceftriaxone in children with enteric fever on the basis of defervescence within 72 hours of commencement of treatment. Duration and Place of Study: This randomized controlled trial was carried out from 15th May to 15th November 2017 in pediatrics units of Benazir Bhutto Shaheed Teaching Hospital Abbottabad and Jinnah International Hospital Abbottabad. Methodology: 90 children with uncomplicated enteric fever were admitted and divided randomly into two groups, Group A was administered I/V Ceftriaxone 75mg/kg OD and Group B was given I/V Ciprofloxacin 10mg/kg BD for seven days. Response to drug was taken as defervescence within 72 hours while continued fever after 72 hours was taken as no response. The data was analyzed by using SPSS Version 21.00. Results: In our research study 53(58.9%) children were male and 37(41.1%) patients were female. The mean age was 8.43±3.17 years encompassing 4 to 14 years, mean weight of the patients in kg was 29.54±10.8 kg. Efficacy of ceftriaxone group was 93.3% while in ciprofloxacin group 62.2% patients became afebrile in 72 hours. The proportion of achieving defervescence within 72 hours was higher with ceftriaxone than with ciprofloxacin Conclusion: Ceftriaxone is more efficacious in terms of achieving defervescence than ciprofloxacin in children having enteric fever.

scholarly journals The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2097
Author(s):  
Gennaro Nappo ◽  
Domenico Borzomati ◽  
Alessandro Zerbi ◽  
Paola Spaggiari ◽  
Ugo Boggi ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Randomized Study ◽  
Periampullary Cancer ◽  
Significant Prognostic Factor ◽  
Prognostic Role ◽  
R1 Resection ◽  
Group A ◽  
Group B

Background: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. Methods: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. Results. One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. Conclusions. The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.

Effects of chronic long-acting bromocriptine treatment on liveweight, voluntary food intake, coat growth and breeding season in non-pregnant red deer hinds

1988 ◽  
Vol 119 (3) ◽  
pp. 413-420 ◽  
Author(s):  
J. D. Curlewis ◽  
A. S. I. Loudon ◽  
J. A. Milne ◽  
A. S. McNeilly
Keyword(s):  
Food Intake ◽  
Breeding Season ◽  
Red Deer ◽  
Vehicle Group ◽  
High Dose ◽  
Group A ◽  
Long Acting ◽  
Group B ◽  
Voluntary Food Intake

ABSTRACT Seventeen red deer hinds were housed in individual pens and from 28 February until 11 November were injected each week with vehicle (group A; n = 6) or 5 (group B; n = 6) or 12·5 mg (group C; n = 5) of a long-acting formulation of bromocriptine. Liveweight and voluntary food intake (VFI) were recorded for each hind, and blood was collected for determination of progesterone, prolactin, tri-iodothyronine (T3) and cortisol concentrations by radioimmunoassay. Treatment with the high dose of bromocriptine was associated with a significant (P <0·05) reduction in VFI, with the effect being greatest between March and July. There was no treatment effect on liveweight, but there was a significant (P <0·01) interaction between time and treatment due to the faster rate of weight gain in control animals at the beginning of the experiment. Changes in liveweight could be explained by changes in VFI rather than by changes in the efficiency of utilization of intake. Termination of the breeding season was significantly (P <0·01) delayed by 54 days in group C hinds. Growth of the summer coat and subsequent winter coats was delayed by 1 and 3 months respectively in group C hinds, and in groups B and C the duration that animals were in summer coat was increased by about 1 month. The seasonal increase in prolactin concentrations was seen in all groups, but levels were significantly (P <0·05) lower in group C hinds. Concentrations of T3 and cortisol were not affected by bromocriptine. J. Endocr. (1988) 119, 413–420

Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma.

1995 ◽  
Vol 13 (8) ◽  
pp. 1958-1965 ◽  
Author(s):  
R J Motzer ◽  
P Lyn ◽  
P Fischer ◽  
P Lianes ◽  
R L Ngo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Plasma Concentrations ◽  
Advanced Renal Cell Carcinoma ◽  
Reversal Agent ◽  
Group A ◽  
Group B ◽  
Mdr Reversal

PURPOSE The reduced cardiac toxicity of the dextro-(d-) stereoisomer of verapamil (dexverapamil; Knoll Pharmaceuticals, Whippany, NJ) warrants its study as a potential multidrug-resistance (MDR) reversal agent. PATIENTS AND METHODS Twenty-three patients with advanced renal cell carcinoma (RCC) were treated with vinblastine at a dose of 0.11 mg/kg intravenous (IV) bolus injection on days 1 and 2 every 21 days. Dexverapamil was added to subsequent cycles after resistance had been demonstrated. Dexverapamil treatment was begun 18 hours before day 1 of vinblastine administration and was given orally every 6 hours for 12 doses. Patients in group A were treated with a dose of 120 mg/m2, and those in group B were treated with 180 mg/m2 plus dexamethasone; plasma concentrations achieved in patients were correlated with in vitro effects. RESULTS Toxicities included hypotension, asymptomatic bradycardia, and mild atrioventricular conduction delays, although one patient had dexverapamil discontinued for grade IV congestive heart failure. There were no partial or complete responses. The mean day-1 serum dexverapamil plus norverapamil plasma concentrations were 2,575 ng/mL (range, 697 to 6,015 ng/mL) for group A and 1,654 ng/mL (range, 710 to 4,132 ng/mL) for group B at the time of vinblastine administration. These concentrations were in the range of those that reversed vinblastine resistance in vitro. CONCLUSION The advantage of dexverapamil as an MDR reversal agent is its potential for achieving desired blood levels with substantially less toxicity than the racemic mixture of verapamil. Based on tolerability, it is a suitable drug for further study in clinical trials of malignancies other than RCC that attempt to achieve MDR reversal. The dose of 120 mg/m2 given orally every 6 hours, with dose escalation based on individual tolerance, represents a feasible schedule to be considered for such studies.

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 &gt;1.2 mg/L, sensitivity = 80%, specificity = 91%; and for group B at cysC &gt;1.4 mg/L, sensitivity = 87%, specificity = 100%) was numerically superior to that for SCR measurement (for group A at SCR &gt;8.0 mg/L, sensitivity = 67%, specificity = 100%; and for group B at SCR &gt;9.0 mg/L, sensitivity = 91%, specificity = 91%), using a reference value for normal GFR of CIN &gt; 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.

Hypokalemia alters sex hormone and gonadotropin levels: evidence that FSH may be required for luteinization

1998 ◽  
Vol 275 (6) ◽  
pp. E1037-E1045
Author(s):  
Francisco Tejada ◽  
Asunción Cremades ◽  
Manuel Avilés ◽  
Maria T. Castells ◽  
Rafael Peñafiel
Keyword(s):  
Luteinizing Hormone ◽  
Follicle Stimulating Hormone ◽  
Combined Treatment ◽  
Gonadotropin Releasing Hormone ◽  
Sex Hormone ◽  
Plasma Progesterone ◽  
Progesterone Secretion ◽  
Potassium Gradient ◽  
Deficient Mice ◽  
Estradiol Levels

Hypokalemia produced different effects on steroid sex hormone concentrations in plasma and ovary in the mouse. Estradiol levels were slightly increased, whereas circulating progesterone was markedly decreased in all estrous periods. The preovulatory surge of gonadotropins and the secondary surge of follicle-stimulating hormone (FSH) at estrus were also decreased, but basal levels of both gonadotropins were unaffected. Supplementation with luteinizing hormone (LH), FSH, or gonadotropin-releasing hormone (GnRH) at proestrus rapidly normalized plasma and ovarian progesterone levels at this stage of the estrous cycle. Plasma progesterone levels at diestrus were restored only by combined treatment, at the periovulatory stage, with LH and FSH or GnRH but not by LH or FSH alone. The results demonstrate a lack of steroidogenic activity in the corpus luteum of the potassium-deficient mice and, furthermore, that FSH plays an important role in luteinization in the hypokalemic mice. We conclude that alteration of the transcellular potassium gradient may affect the regulation of the periovulatory surge of gonadotropins and progesterone secretion, probably by altering the release of GnRH from the hypothalamus. In addition, the results suggest that FSH may play a certain role as a luteotropic hormone in mice.

Protein S secretion differences of missense mutants account for phenotypic heterogeneity

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 173-179
Author(s):  
Yolanda Espinosa-Parrilla ◽  
Tomio Yamazaki ◽  
Nùria Sala ◽  
Björn Dahlbäck ◽  
Pablo Garcı́a de Frutos
Keyword(s):  
Plasma Concentrations ◽  
Protein S ◽  
Phenotypic Heterogeneity ◽  
Protein S Deficiency ◽  
In Vitro Synthesis ◽  
Low Protein ◽  
S Deficiency ◽  
Group A ◽  
Group B

To elucidate the molecular background for the heterogeneity in protein S plasma concentrations observed in protein S deficient individuals, the in vitro synthesis of recombinant protein S missense mutants was investigated. Six different naturally occurring mutations identified in the protein S gene (PROS1) of thrombosis patients were reproduced in protein S cDNA by site directed mutagenesis. Two mutants, G441C and Y444C (group A), were associated with low total plasma concentration of protein S. Modestly low protein S was found in families with R520G and P626L (group B) mutants. T57S and I518M (group C), which was associated with marginally low protein S, did not segregate with protein S deficiency in the respective families, raising doubts as to whether they were causative mutations or rare neutral variants. The 6 protein S mutants were transiently expressed in COS 1 cells. The Y444C mutant showed the lowest level of secretion (2.5%) followed by the G441C mutant (40%). Group B demonstrated around 50% reduction in secretion, whereas group C mutants showed normal secretion. Pulse-chase experiments demonstrated impaired protein S processing with intracellular degradation and decreased secretion into the culture media of group A and B mutants. Interestingly, there was a good correlation between in vitro secretion and the concentration of free protein S in the plasma of heterozygous carriers. These results demonstrate impaired protein S secretion to be an important mechanism underlying hereditary protein S deficiency and that variations in protein secretion is a major determinant of the phenotypic heterogeneity observed in protein S deficiency. (Blood. 2000;95:173-179)

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