INHIBIN BIOACTIVITY IN HUMAN TESTICULAR EXTRACTS

1987 ◽  
Vol 115 (2) ◽  
pp. R9-R12 ◽  
Author(s):  
B.J.B. Simpson ◽  
C.G. Tsonis ◽  
F.C.W. Wu

ABSTRACT Inhibin bioactivity was measured in human testicular extracts by a sensitive sheep pituitary cell bioassay. The relationship between testicular inhibin bioactivity, daily sperm production (DSP) and plasma concentrations of FSH, LH, testosterone and oestradiol were examined. The mean level of testicular inhibin bioactivity was 4.4 ±1.3 U/g (mean ± SD) with a significantly lower value in those who received radiotherapy (3.2 ± 1.4 U/g) than in the untreated group (4.8 ± 1.1 U/g). In contrast to the rat, human testicular inhibin bioactivity was not significantly correlated to FSH or DSP. These findings suggest that inhibin may have a complex role in normal and/or pathological testicular function.

2009 ◽  
Vol 103 (2) ◽  
pp. 249-255 ◽  
Author(s):  
Jie Cao ◽  
Ying Zhang ◽  
Wei Chen ◽  
Xiujuan Zhao

Epidemiological studies suggest that a diet high in flavonoids protects against chronic diseases such as CVD and cancer. The objective of the present study was to evaluate the relationship between the intake of quercetin, kaempferol, isorhamnetin, apigenin and luteolin and their corresponding plasma concentrations, and further to explore whether these flavonoids can serve as biomarkers of their intake. Flavonoid intake and their plasma concentrations were analysed in ninety-two subjects consuming their habitual diet. Flavonoid intake was estimated with 7-d dietary records using available data on the flavonoid content of food. Plasma flavonoid concentrations were quantified by HPLC. In addition, we undertook a dietary intervention study to investigate plasma apigenin concentration after the consumption of celery leaf. The mean intake estimates of quercetin, kaempferol, isorhamnetin, apigenin and luteolin amounted to 13·58, 14·97, 12·31, 4·23 and 8·08 mg/d, respectively. The corresponding mean plasma concentrations were 80·23, 57·86, 39·94, 10·62 and 99·90 nmol/l. The mean 7 d intake of five flavonoids was positively correlated to their corresponding plasma concentrations, with correlation coefficients ranging from 0·33 to 0·51 (P < 0·05). In the dietary intervention study, the plasma apigenin concentration rose after celery leaf ingestion, and fell within 28 h to below the limit of detection (2·32 nmol/l). The present results suggest that quercetin, kaempferol, isorhamnetin, apigenin and luteolin are bioavailable from the diet. The levels of fasting plasma flavonoids seem to be suitable biomarkers of short-term intake. The combination of plasma flavonoids with their intake may prove useful when the possible health-protective effects of flavonoids are studied.


Reproduction ◽  
2001 ◽  
pp. 239-247 ◽  
Author(s):  
EJ Peirce ◽  
WG Breed

The plains rat, Pseudomys australis, and the spinifex hopping mouse, Notomys alexis, show marked differences in the size of their testes and in the number of spermatozoa within the epididymides. In the present study, the dynamics of sperm production and the duration of sperm transit along the male excurrent ducts were compared between these two species. The durations of the cycle of the seminiferous epithelium, spermatogenesis and sperm transit were determined by tracking cells using autoradiography after [(3)H]thymidine incorporation. Daily sperm production was determined from counts of testicular spermatids after homogenization and further estimates of sperm transit were obtained by dividing sperm reserves within the various regions of the extratesticular ducts by the daily sperm production of the attached testis. In the plains rat, the mean duration of the cycle of the seminiferous epithelium was 11.2 days, the duration of spermatogenesis was 45 days, daily sperm production was 2.6 x 10(7) spermatozoa per gram of testis and epididymal transit of spermatozoa took approximately 9 days (caput 0.8 days; corpus 1.5 days; cauda 6.5 days). In contrast, in the hopping mouse, the mean duration of the cycle of the seminiferous epithelium was 14 days, the duration of spermatogenesis was 56 days and daily sperm production per gram of testis was < 1.0 x 10(7). Epididymal transit of spermatozoa was completed in about 4 days (caput + corpus < 1 day; cauda 3 days); however, spermatozoa may be stored for an additional 1.5-2.0 days in the vas deferens. These results indicate that, in addition to small testes, the hopping mouse shows a low efficiency of sperm production, a relatively long duration of spermatogenesis and rapid passage of spermatozoa through the epididymis, all of which contribute to low epididymal sperm counts. These data are considered in relation to interspecific differences in sperm competition.


1981 ◽  
Vol 88 (2) ◽  
pp. 255-262 ◽  
Author(s):  
R. GHANADIAN ◽  
C. M. PUAH

The relationship between the concentrations of oestradiol, testosterone, dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol in circulating blood and prostatic tissues was studied in patients with benign prostatic hypertrophy (BPH) and carcinoma of the prostate. All steroids were measured by radioimmunoassay. In patients with BPH the tissue concentrations of oestradiol, testosterone, DHT and 5α-androstane-3α,17β-diol expressed per kg wet weight were 228·6 ± 7·4 (s.e.m.) pmol, 1·29 ± 0·06 nmol, 25·61 ± 1·15 nmol and 1·43 ± 0·10 nmol respectively. The corresponding values for carcinomatous tissues were 380·1 ± 19·4 pmol, 7·20 ± 1·10 nmol, 12·32 ± 1·56 nmol and 1·99 ± 0·32 nmol. Significant differences (t-test) were found between the mean concentrations of oestradiol (P <0·001), testosterone (P <0·001), DHT (P <0·001) and 5α-androstane-3α,17β-diol (P <0·05) in prostatic tissues of these two groups of patients. Significant negative correlations were observed between the tissue concentrations of oestradiol and DHT (r = −0·49, P <0·05) and between oestradiol and 5α-androstane-3α,17β-diol (r = −0·44, P <0·05) in BPH but not in malignant tissues. The plasma concentrations of oestradiol, testosterone, DHT and 5α-androstane-3α,17β-diol in patients with BPH were 147·4 ± 6·9 pmol/l,18·4 ± 1·2 nmol/l,2·6 ± 0·2 nmol/l and 0·84 ± 0·04 nmol/l respectively. The corresponding values for patients with carcinoma of the prostate were 145·5 ± 17·0 pmol/l, 17·3 ± 2·4 nmol/l, 2·0 ± 0·3 nmol/l and 0·56 ± 0·06 nmol/l respectively. The mean plasma 5α-androstane-3α,17β-diol was found to be significantly higher in patients with BPH (P <0·01) than with carcinoma. No significant correlations were found between the tissue concentrations of these steroids and the corresponding plasma values, which suggested that their metabolism and accumulation in prostatic tumours are independent of their plasma concentrations.


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.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2907-2907
Author(s):  
William C. Oliver ◽  
Gregory A. Nuttall ◽  
Sheldon Goldstein ◽  
Mark H. Ereth ◽  
Jeffrey L. Winters ◽  
...  

Abstract A device that would provide a rapid evaluation of hemostasis would greatly aid physicians in making scientific decisions regarding transfusion therapy; especially with perioperative bleeding. We performed a prospective in-vitro study with reconstituted, recalcified whole blood (n = 6) separated into samples containing specific deficiencies in platelets, plasma, lyophilized platelets and lyophilized plasma such that the concentrations of the specific platelet or plasma were 0%, 10%, 30%, 50%, and 100%. The whole blood was obtained from consenting healthy volunteers. Samples from the various concentrations of the reconstituted blood were subjected to the following point of care coagulation tests: activated clotting time (ACT), thromboelastogram (TEG), laboratory prothrombin time (PT), laboratory activated partial thromboplastin time (APTT) and Signature+ PT. ACT’s were performed for each of four celite doses (1.5 mg, 3.0 mg, 6.0 mg and 12 mg celite). The four dose celite ACT’s were performed in duplicate and the mean recorded. The TEG was performed in duplicate, and the mean was recorded. The signature+ PT was performed in duplicate, and the mean recorded. The laboratory PT, aPTT, Platelet Count and Fibrinogen were performed once each. ACT values were analyzed within each of the three preparations using analysis of variance. This assessed the strength of the relationship between blood constituent concentration and ACT, and determined whether this relationship differed across varying amounts of celite. Other coagulation parameters including TEG (mA), PT and APTT were analyzed using analysis of variance with a single term for blood constituent concentration. This model determined the strength of the relationship between these coagulation parameters and blood constituent concentration. In addition, the kaolin activated TEG and the signature+ PT was evaluated to determine the strength of the relationship between these tests and the variations in platelet and plasma concentrations. There was a significant correlation between the plasma, platelets and lyophilized plasma concentrations and ACT results (all p < 0.001). There was a significant correlation between plasma platelets and lyophilized plasma and the TEG MA and angle (all p < 0.028). There was a significant correlation between laboratory PT and APTT and plasma, platelets, and lyophilized plasma, lyophilized platelets (all p < 0.001). There was a significant correlation between the Signature+ PT and plasma, lyophilized platelets, and lypholized plasma and platelets (all p < 0.005), (figure 1). A better point of care coagulation device that is based on in-vitro additions of various therapies, and comparison of their effects on coagulation tests may provide better treatment of the bleeding patient. The Signature+ PT could provide the endpoint for such a device whereas the ACT was nonspecific and had a small change in results with large changes in plasma concentration. The additional benefit of lypholized plasma to behave similarly to human plasma may allow such a device to be built. Figure Figure


Zygote ◽  
2016 ◽  
Vol 24 (5) ◽  
pp. 783-793 ◽  
Author(s):  
Nathália L.M. Lara ◽  
Ivan C. Santos ◽  
Guilherme M.J. Costa ◽  
Dirceu A. Cordeiro-Junior ◽  
Antônio C. G. Almeida ◽  
...  

SummaryThe spiny rat (Proechimys guyannensis) is a neotropical rodent that is used in biomedical research, particularly research related to chronic resistance to epilepsy and infectious diseases. To our knowledge, there are few reports concerning the reproductive biology of this species. Therefore, besides providing basic biometric and morphometric data, in the present study we investigated testis function and spermatogenesis in adult spiny rats. The mean testis weight and gonadosomatic index obtained were 1.63 ± 0.2 g and 1.15 ± 0.1% respectively. Based on the development of the acrosomic system, 12 stages of the seminiferous epithelium cycle were characterized. Stages VI and VII presented the highest frequencies (~17–19%), whilst stages II to V showed the lowest frequencies (~2–4%). The most advanced germ cell types labelled at 1 h or 20 days after BrdU injections were respectively preleptotene/leptotene spermatocytes at stage VII and elongated spermatids at stage III. The mean duration of one cycle was 7.5 ± 0.01 days and the entire spermatogenic process lasted 33.7 ± 0.06 days (~4.5 cycles). The seminiferous tubules (ST) occupied ~96 ± 1% of the testis parenchyma, whereas Leydig cells comprised only 1.5 ± 0.4%. The number of Sertoli cells (SC) per testis gram and the SC efficiency (spermatids/SC) were respectively 78 × 106 ± 11 × 106 and 7.9 ± 1. The daily sperm production per testis gram (spermatogenic efficiency; daily sperm production (DSP)/g/testis) was 78 × 106 ± 8 × 106. To our knowledge, this spermatogenic efficiency is among the highest found for mammals investigated to date and is probably related to the very short duration of spermatogenesis and the very high ST percentage and SC number obtained for this species.


CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 274-274
Author(s):  
Azmi Nasser ◽  
Shamia L. Faison ◽  
Tesfaye Liranso ◽  
Toyin Adewole ◽  
Maurizio Fava ◽  
...  

Abstract:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) under investigation as a treatment for attention-deficit/hyperactivity disorder (ADHD). One concern for any new drug is prolongation of the QT interval, which is associated with increased risk for potentially very harmful ventricular cardiac arrhythmias such as torsades de pointes (TdP). The objective of this study was to assess the effects of SPN-812 at a supratherapeutic dose (1800 mg once daily [QD]) on cardiac repolarization (QTc) in healthy adults.Method:This study was a Phase 1, double-blind (except for the positive control moxifloxacin), randomized, 3-period, 6-sequence crossover design in healthy adult male and female subjects evaluating the electrocardiographic effects of SPN-812. Subjects were randomized to receive a sequence of all 3 treatments – placebo, 400 mg moxifloxacin (positive control), and 1800 mg SPN-812 (supratherapeutic dose). Treatment was given for 2 consecutive days (separated by a washout of at least 4 days). The primary endpoint was based on concentration-QTc effect modeling, evaluating the relationship between plasma concentrations of SPN-812 and its metabolite 5-hydroxyviloxazine glucuronide (5-HVLX-gluc) with the placebo-adjusted change from baseline in QTcI, ΔΔQTcI (QT interval corrected for HR based on the individual-specific QT interval correction method). Secondary endpoints included time point change from baseline in QTcI, QTcF, HR, PR, and QRS; evaluation of the relationship between the plasma concentration of viloxazine and 5-HVLX-gluc and the placebo-adjusted change from baseline in HR, PR, QRS, and QTcF; evaluation of the relationship between the plasma concentration of moxifloxacin and ΔΔQTcI to demonstrate assay sensitivity; and changes in ECG morphology. Safety endpoints included assessment of adverse events and other parameters.Results:The relationship between ΔΔQTcI and viloxazine plasma concentration demonstrated a negative slope (p=0.0012). Predicted mean ΔΔQTcI (2-sided 90% CI) for SPN-812 was -9.7 ms (-11.3, -8.1) at the mean Cmax of 12.4 μg/mL. The relationship of 5-HVLX-gluc and ΔΔQTcI similarly demonstrated a predicted negative slope (p=0.0007) with a predicted mean ΔΔQTcI (2-sided 90% CI) of -9.2 ms (-10.8, -7.8) at the mean Cmax of 10.0 μg/mL. Assay sensitivity was confirmed. Concentration-effect modeling demonstrated no relationship between plasma concentrations of viloxazine and 5-HVLX-gluc and other ECG parameters. The secondary time point analyses demonstrated no effect of SPN-812 on QTcI or other ECG intervals. SPN-812 produced no changes in ECG T wave or U wave morphology.Conclusions:Data from this Phase 1 thorough QT study demonstrate that a supratherapeutic dose of SPN-812, 1800 mg QD, has no effect on cardiac repolarization or other ECG parameters, and is thus not associated with a risk for cardiac arrhythmias such as TdP.Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.


Author(s):  
Mariusz Piechota ◽  
Maciej Banach ◽  
Robert Irzmański ◽  
Małgorzata Misztal ◽  
Jacek Rysz ◽  
...  

AbstractThe aim of this study was to find the relationship between N-terminal brain natriuretic propeptide (NT-proBNP), procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations in septic patients. This was a prospective study, performed at Medical University Hospital No. 5 in łódź. Twenty patients with sepsis and severe sepsis were included in the study. N-terminal brain natriuretic propeptide, procalcitonin and C-reactive protein concentrations, and survival were evaluated. In the whole studied group (128 measurements), the mean NT-proBNP, procalcitonin and C-reactive protein concentrations were, respectively: 140.80±84.65 pg/ml, 22.32±97.41 ng/ml, 128.51±79.05 mg/l. The correlations for the NT-proBNP level and procalcitonin and C-reactive protein levels were 0.3273 (p<0.001) and 0.4134 (p<0.001), respectively. NT-proBNP levels correlate with PCT and CRP levels in septic patients. In the survivor subgroup, the mean NT-proBNP plasma concentrations were significantly lower than in the non-survivor subgroup.


Reproduction ◽  
1994 ◽  
Vol 100 (1) ◽  
pp. 315-321 ◽  
Author(s):  
L. Johnson ◽  
G. K. Carter ◽  
D. D. Varner ◽  
T. S. Taylor ◽  
T. L. Blanchard ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document