scholarly journals Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 313 ◽  
Author(s):  
Rihong Guo ◽  
Fang Chen ◽  
Cheng Mei ◽  
Zicun Dai ◽  
Leyan Yan ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Reproductive Performance ◽  
Luteal Phase ◽  
Low Dose ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
High Dose ◽  
Reproductive Hormone ◽  
Conception Rates

This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.

FSH secretory pattern and degree of concordance with LH in amenorrheic, fertile, and postmenopausal women

1993 ◽  
Vol 264 (5) ◽  
pp. E776-E781 ◽  
Author(s):  
A. D. Genazzani ◽  
F. Petraglia ◽  
C. Volpogni ◽  
G. D'Ambrogio ◽  
F. Facchinetti ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Luteal Phase ◽  
Follicle Stimulating Hormone ◽  
Plasma Concentrations ◽  
Gonadal Steroids ◽  
Reference Groups ◽  
Temporal Coupling ◽  
Secretory Pattern ◽  
Normal Controls ◽  
Fertile Women

Pulsatile secretion of gonadotropin was investigated in amenorrheic patients and in fertile and postmenopausal women to assess both follicle-stimulating hormone (FSH) episodic secretion and its temporal coupling with luteinizing hormone (LH). Three groups of amenorrheic patients were studied: hyperandrogenic (n = 20), hypogonadotropic (n = 51), and normogonadotropic (n = 31). Nineteen fertile women (during the follicular and luteal phases of the cycle) and sixteen postmenopausal women were investigated as reference groups. All subjects demonstrated the presence of a distinct pulsatile pattern with LH and FSH pulses/4 h as follows: hyperandrogenic 3.95 +/- 0.26 and 3.85 +/- 0.2, hypogonadotropic 3.76 +/- 0.26 and 3.9 +/- 0.16, normogonadotropic 3.5 +/- 0.2 and 3.9 +/- 0.17 LH and FSH pulses/4 h, respectively (means +/- SE). Normal controls showed 4.1 +/- 0.2 and 3.1 +/- 0.2 pulses/4 h for LH (P < 0.05) and 3.2 +/- 0.1 and 3.6 +/- 0.3 pulses/4 h for FSH, during follicular and luteal phases, respectively. Postmenopausal women showed 3.6 +/- 0.2 and 3.0 +/- 0.3 pulses/4 h for LH and FSH, respectively. Specific concordance (SC) index demonstrated that LH and FSH were significantly and simultaneously secreted in all groups. Conversely, LH and FSH were not temporally related during the luteal phase. In conclusion, we report a distinct FSH episodic secretion and its temporal linkage with LH pulses irrespective of plasma concentrations of gonadal steroids in secondary amenorrhea.

Effects of acetylsalicylic acid on pulmonary vascular tone and membrane permeability in blood-perfused dog lung

1993 ◽  
Vol 75 (6) ◽  
pp. 2561-2569 ◽  
Author(s):  
K. Kambara ◽  
M. Arakawa ◽  
T. Segawa ◽  
F. Ando ◽  
M. Ohno ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Extravascular Lung Water ◽  
Vascular Tone ◽  
Low Dose ◽  
Pressor Response ◽  
Plasma Concentrations ◽  
High Dose ◽  
Constant Flow ◽  
Lung Water ◽  
Pulmonary Vasoconstriction

We studied the effects of acetylsalicylic acid (ASA) on pressor response, microvascular filtration coefficient (Kf), extravascular lung water, and plasma concentrations of cyclooxygenase- and 5-lipoxygenase-derived products in 21 blood-perfused dog lungs with constant flow. The lungs were perfused for 1 h with an intrapulmonary injection of saline as vehicle (n = 5), a low dose of ASA [136 +/- 25 (SD) micrograms/ml perfusate; n = 5], a high dose of ASA (1,006 +/- 278 micrograms/ml perfusate; n = 6), or alloxan (1,000 mg; n = 5). Alloxan significantly increased Kf and extravascular lung water, whereas neither the low nor high dose of ASA increased Kf or extravascular lung water. The ASA-induced increase in vascular resistance did not correlate with the extent of the decrease in perfusate 6-keto-prostaglandin F1 alpha or the ratio of perfusate 6-ketoprostaglandin F1 alpha to thromboxane B2. Moreover, ASA did not enhance the generation of perfusate leukotrienes B4, D4, or E4. We conclude that pulmonary microvascular permeability is unaltered by ASA and that neither the decrease in plasma prostacyclin nor the increase in plasma sulfidopeptide leukotrienes may account for ASA-induced pulmonary vasoconstriction.

Effect of human recombinant superoxide dismutase on canine myocardial infarction

1990 ◽  
Vol 258 (2) ◽  
pp. H369-H380 ◽  
Author(s):  
B. S. Patel ◽  
M. O. Jeroudi ◽  
P. G. O'Neill ◽  
R. Roberts ◽  
R. Bolli
Keyword(s):  
Superoxide Dismutase ◽  
Infarct Size ◽  
Low Dose ◽  
Coronary Occlusion ◽  
Plasma Concentrations ◽  
Control Group ◽  
High Dose ◽  
Collateral Flow ◽  
Tetrazolium Chloride ◽  
Arterial Blood

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) “low-dose” h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) “high-dose” h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.

Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor

1992 ◽  
Vol 135 (1) ◽  
pp. 91-101 ◽  
Author(s):  
C. B. Gow ◽  
M. Wilkinson ◽  
M. J. Silvapulle ◽  
G. P. M. Moore
Keyword(s):  
Parathyroid Hormone ◽  
Growth Factor ◽  
Fluid Balance ◽  
Low Dose ◽  
Plasma Concentrations ◽  
Urine Volume ◽  
High Dose ◽  
Epidermal Growth ◽  
Higher Doses ◽  
Medium Dose

ABSTRACT The infusion of low doses of epidermal growth factor (EGF) into lactating ewes stimulates water intake and urine volume. The plasma concentrations and daily output of various electrolytes in milk and urine are also affected. We have investigated this further by recording the effects of EGF infusion on fluid balance, electrolyte profiles and plasma concentrations of glucose and parathyroid hormone (PTH) in non-pregnant, non-lactating ewes. Twenty-four animals (n= 8 per group) received infusions of 100 ml saline/day into the jugular vein for 10 days (days 1–10) followed by EGF at a dose rate of either 1 (low dose), 5 (medium dose) or 10 (high dose) μg/kg liveweight per day in 100 ml saline for 5 days (days 11–15). All ewes then received an infusion of 100 ml saline/day for 10 days (days 16–25). Most plasma and urine samples had undetectable concentrations of EGF-immunoreactive material during the periods of saline infusion. During EGF infusion, the highest amounts of EGF infusate excreted in urine were 1·6, 5·9 and 5·6% for ewes in low, medium and high dose groups respectively. Water intake increased by 17% (0·5 kg), 88% (2·5 kg) and 89% (2·3 kg) and urine volume increased by 29% (0·5 kg), 108% (2·2 kg) and 134% (2·1 kg) for the three groups respectively. Fluid balance and feed intake were not affected by EGF infusion, but the output of faecal dry matter was reduced in ewes receiving the two higher doses of EGF. All levels of EGF resulted in hypocalcaemia, increased plasma PTH concentrations and hypermagnesaemia. There was no effect of EGF on plasma concentrations of K+ and glucose or on daily urinary excretion of K+ and Mg2+. The only response to the low dose was a reduced plasma concentration of Na+ and an increased daily urinary urate excretion. The two higher doses increased the daily urinary excretion of Na+, PO43− and urate, but had no effect on the respective concentrations in plasma. Urinary Ca2+ excretion was reduced only during infusion of the medium dose of EGF. The responses of most variables were similar during infusion of the medium and high doses of EGF. All three doses of EGF induced polydipsic and diuretic responses in ewes, and infusions of 5–10 μg EGF/kg liveweight per day affected renal excretion of Ca2+, Na+ and PO3−4. We interpret the responses of the kidney and plasma PTH concentrations as a means of maintaining the homeostasis of plasma profiles of electrolytes. Journal of Endocrinology (1992) 135, 91–101

scholarly journals Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women

2021 ◽  
Author(s):  
Steve Pawsey ◽  
Edouard Gregory Mills ◽  
Elizabeth Ballantyne ◽  
Kirsteen Donaldson ◽  
Mary Kerr ◽  
...  
Keyword(s):  
Luteal Phase ◽  
Hormone Secretion ◽  
Reproductive Hormones ◽  
Controlled Study ◽  
Vasomotor Symptoms ◽  
Reproductive Hormone ◽  
Novel Therapy ◽  
Serum Progesterone ◽  
Hormone Levels ◽  
Healthy Women

Abstract Context The ideal therapy for endometriosis (EM) and uterine fibroids (UF) would suppress estrogenic drive to the endometrium and myometrium, whilst minimizing vasomotor symptoms and bone loss associated with current treatments. An integrated neurokinin-kisspeptin system involving Substance P and neurokinin B acting at the neurokinin (NK) receptors 1 and 3, respectively, modulates reproductive hormone secretion and represents a therapeutic target. Objective To assess the effects of the novel NK1,3 antagonist elinzanetant on reproductive hormone levels in healthy women. Design Randomized, single-blinded, placebo-controlled study. Participants/Intervention Thirty-three women attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3/4, 9/10, 15/16 and 21/22 to measure serum reproductive hormones. In cycle 2, women were randomized to receive once daily oral elinzanetant 40, 80, 120 mg or placebo (N=8 or 9 per group). Results Elinzanetant dose-dependently lowered serum luteinizing hormone, estradiol (120 mg median change across cycle: -141.4 pmol/L, P=0.038) and luteal phase progesterone (120 mg change from baseline on day 21/22: -19.400 nmol/L, P=0.046). Elinzanetant 120 mg prolonged the cycle length by median of 7.0 days (P=0.023). Elinzanetant reduced the proportion of women with a luteal phase serum progesterone concentration &gt;30 nmol/L (a concentration consistent with ovulation) in a dose-related manner in cycle 2 (P=0.002). Treatment did not produce vasomotor symptoms. Conclusions NK1,3 receptor antagonism with elinzanetant dose-dependently suppressed the reproductive axis in healthy women, with the 120 mg dose lowering estradiol to potentially ideal levels for UF and EM. As such, elinzanetant may represent a novel therapy to manipulate reproductive hormone levels in women with hormone driven disorders.

High-Dose Ascorbic Acid Decreases Cholesterolemic Factors of an Atherogenic Diet in Guinea Pigs

2007 ◽  
Vol 77 (2) ◽  
pp. 125-129
Author(s):  
Filis ◽  
Anastassopoulou ◽  
Sigala ◽  
Theodorou ◽  
Manouras ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Guinea Pigs ◽  
Low Dose ◽  
Plasma Concentrations ◽  
Atherogenic Diet ◽  
High Dose ◽  
Low Density ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Background: The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Methods: Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Results: Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). Conclusion: High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Pharmacokinetics of RO5072759 (GA101) In Patients with Relapsed/Refractory CD20+ Malignant Disease (Phase I/II Study BO20999)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1833-1833
Author(s):  
Georgina Meneses-Lorente ◽  
David Carlile ◽  
Joe Birkett ◽  
Michael K. Wenger ◽  
Guillaume Cartron ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Dose Escalation ◽  
Low Dose ◽  
Cell Lymphoma ◽  
Plasma Concentrations ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Serum Samples ◽  
Flat Dose

Abstract Abstract 1833 Background and Objective: GA101 is the first type II glycoengineered and humanized monoclonal anti-CD20 antibody to enter clinical trials. BO20999 is an open label multicenter, phase I/II study evaluating GA101 safety, tolerability and pharmacokinetics in patients with relapsed/refractory CD20+ NHL/CLL. Phase I results showed an end of treatment response rate (EOR) of 33% in NHL patients (Salles G. et al, Blood [ASH Annual Meeting Abstracts], Nov 2009; 114: 1704). Phase II results recently reported for indolent NHL showed an EOR of 55% and 17% for GA101 monotherapy given at a high dose (HD) and a low dose (LD), respectively supporting a possible dose-response relationship (Salles G. et al, Haematologica 2010; 95[suppl.2]:229, abs. 0558). Here within, we describe the results of analyses exploring GA101 exposure and response in indolent NHL patients. Study Population and Assessments: Phase I Study: 21 patients with CD20+B-lymphoproliferative disorders including [follicular lymphoma (fNHL), mantle cell lymphoma (MCL), diffused large B cell lymphoma (DLBCL), Waldenstrom's macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and lymphoplasmacytoid lymphoma received intravenous GA101 as a flat dose in a safety driven dose escalation 3+3 design (from 50 mg to 2000 mg). Phase II Study: 40 indolent NHL patients were randomized to receive low dose (LD) GA101 (n=18) or a high dose (HD) (n=22). GA101 was given on d1, d8, d22 and q21 days for a total of 9 infusions as a flat dose. In the LD cohort, GA101 was 400 mg; in the HD cohort, d1 and d8 were 1600 mg and subsequently 800 mg thereafter. Pharmacokinetic Assessments: GA101 serum samples were taken prior to and immediately after each infusion, for all eight cycles. Additional serum samples were taken between days 1–21 during cycle 1 and between days 1–25 during cycle 8. Serum levels of GA101 were measured by ELISA. Results: Phase I GA101 PK data: Although a high degree of variability was observed in the GA101 plasma concentrations, due in part to inter-individual differences, mean GA101 plasma concentration increased with dose. Phase II GA101 PK data: As anticipated, higher GA101 plasma concentrations were observed in the HD group compared to the LD group (Figure 1). In the HD group after cycle 2 mean Cmax and Cmin values plateaued whereas in the LD group both mean Cmax and Cmin values continued to increase between cycles 2 and 8. Given there were some responses (n=3) in the LD group, a dose of 400 mg has some biological effects; however target saturation appears incomplete, whereas the HD group indicates sustained target saturation. Responding patients from both dose groups appeared to have higher plasma concentrations compared to non-responding patients (Figure 2). Interestingly, responding patients showed increased plasma concentrations over time whereas there was a decrease in plasma concentrations in the non-responding patients. Moreover, further analysis in the HD group demonstrated that non-responding patients have the highest peak to trough concentration ratios indicating a higher rate of GA101 elimination compared to the responding patients (Figure 3). Overall, these data indicate that responding patients appear to eliminate GA101 slower compared to non-responding patients. Conclusions: Overall, GA101 plasma concentrations appeared to increase with dose in both Phase I (dose escalation) and Phase II parts of BO20999. Accumulation of GA101 levels in plasma was observed from 400/800 mg to 1200/2000 mg dose group which was consistent with target saturation. GA101 plasma profiles indicated that responding iNHL patients appeared to eliminate GA101 slower compared to non-responding iNHL patients. Disclosures: Wenger: Roche: Employment. Cartron:Roche: Consultancy, Honoraria; GSK: Honoraria. Morschhauser:Roche: Consultancy, Honoraria. Salles:Roche: Consultancy, Honoraria.

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