Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi’s sarcoma (KS) cells. However, the mechanism of the anti-KS activity achieved with these preparations remains unclear. The results of clinical studies using commercial hCG preparations in human KS are also highly contradictory. The apparent controversy between different studies may be due to the fact that pro- and anti-KS components are present in varying proportions in different hCG preparations. As certain hCG preparations could not only lack the ability to control KS but also contain some contaminant KS growth factor(s), we suggest a cautious use of crude hCG for the treatment of KS.
Semen samples were obtained by masturbation from 6 chimpanzees and the spontaneously liquefied fraction and the remaining coagulum were studied separately. When semen was collected once or twice a week, large intra-individual variations were observed for all measures. The liquefied fraction represented 26.5 +/- 3.2% (weighted mean +/- s.d.) of the total ejaculate but contained 51.3 +/- 3.8% of all emitted spermatozoa. Fructose concentration was higher in the coagulum than in the liquefied fraction (29.3 +/- 3.0 mumol/ml vs 12.0 +/- 2.7 mumol/ml, P less than 0.001) whereas acid phosphatase was less concentrated in the coagulum than in the liquefied fraction (3.5 +/- 0.3 x 10(3) IU/ml vs 13.0 +/- 0.9 x 10(3) IU/ml, P less than 0.001). L-Carnitine and citrate concentrations did not differ between the two fractions of the ejaculate. When semen collection was repeated every hour for 5 h, the ejaculate volume increased from 2.6 +/- 0.7 to 4.7 +/- 0.6 ml (P less than 0.001), whereas total sperm count decreased from 1278 +/- 872 x 10(6) to 587 +/- 329 x 10(6) (P less than 0.05) between the 1st and the 6th ejaculate. In the spontaneously liquefied fraction, the sperm count decreased from 984 to 369 x 10(6). The 6 successive ejaculates gave a total of 20.2 +/- 7.6 ml and 4278 +/- 2884 x 10(6) spermatozoa. The increase of the ejaculate volume was essentially due to an increase of the volume of the coagulum which closely correlated with total amount of fructose (from seminal vesicles) (r = 0.913, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the results of clinical studies using commercial hCG preparations KS remain highly contradictory. More particularly, some hCG preparations could have a paradoxical growth effect on KS. Such discrepant results may be explained by the fact that the anti-KS activity is not associated with hCG itself but with one or more factors that are co-purified with the hormone. We found here that crude urine from first trimester pregnant women, the current source for commercial hCG, had a growth stimulatory effect on KS cells. By contrast, urine from last trimester pregnant women, from non-pregnant young women, from menopausal women and from men exhibited neither a growth stimulatory nor a growth inhibitory effect on KS cells. The amplitude of this pregnancy urine-associated pro-KS activity/hCG unit was higher than that achieved with clinical-grade hCG preparations. Partial co-purification of pregnancy-associated factors during the extraction procedure of commercial hCG from urine may explain the pro-KS activity achieved with some hCG preparations. We, therefore, suggest a cautious use of hCG purified from pregnancy urine for the treatment of KS.
Apoptosis in human placental villi is reported to increase until close to delivery. However, the involvement of the apoptotic process in the initiation of labor, and more particularly in relation to the decrease in placental perfusion during uterine contractions, remains unknown. The purpose of the study was to examine the reactivity of the apoptotic machinery in term placentae obtained before or after the onset of labor and after in vitro incubations. The incidence of apoptotic nuclei (< 1%) as evidenced by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, and the histological distribution of immunoreactive Bcl-2, Bax, and Bcl-x proteins, were similar in placentae collected after delivery and before the onset of labor and in placental explants maintained overnight at 4 degrees C in a minimal salt-Hepes medium. By contrast, 28% of nuclei contained fragmented DNA when placental explants were incubated overnight at 37 degrees C. This marked increase was associated with a decrease in the intensity of the Bcl-2 immunostaining and an increase in the intensity of Bax and Bcl-x immunostaining. In conclusion, the present study clearly evidences the presence of an active apoptotic machinery in term placental cells that is not involved in normal parturition.
Human chorionic gonadotrophin (hCG) is known to possess thyroid-stimulating activity. The aim of the present study was to assess the role of hCG in stimulating the maternal thyroid gland in the early stages of normal gestation.Thirty euthyroid healthy women were investigated prospectively. In each, conception had been assisted by in vitro fertilization techniques, which allowed for the precise determination of gestational age. Women were subdivided into single (n = 17) and twin (n = 13) pregnancies. Serum intact hCG and its free alpha and beta subunits, TSH and free T4 concentrations were measured at 6, 8, 9, 10, 11, 15, 19, 22 and 32 weeks.In twin pregnancies compared with single pregnancies, peak hCG concentrations (9-11 weeks) were significantly higher (mean +/- SE 171,000 +/- 12,500 vs 65,500 +/- 7600 U/l; P < 0.001), and also much more prolonged. Human CG concentrations above 75,000 U/l lasted for less than 1 week in single, compared with up to 6 weeks in twin pregnancies. Free beta-hCG subunit concentrations paralleled those of intact hCG in both groups. The ratios of free beta-hCG subunit/total hCG were similar in single and twin pregnancies, and did not vary with gestation time. Concerning thyroid function, twin pregnancy was more frequently associated with a lowering of TSH, which was also more profound than in single pregnancies. Furthermore, while free T4 levels remained normal in single pregnancies, they were transiently supranormal (up to 52 pmol/l) in four twin pregnancies.In twin pregnancies the placenta produces larger amounts of hCG for a prolonged period of time than in single pregnancies. Both the amplitude and duration of hCG production (i.e. the global exposure of the thyroid gland to hCG) are responsible for increased thyroidal stimulation, leading more frequently to increased free T4 and suppressed TSH levels. The results emphasize the role of hCG in stimulating maternal thyroid function in the first trimester of pregnancy. Even though the production of a variant hCG molecule with potent thyrotrophic activity cannot be excluded, this hypothesis is not required to explain the data. Clinicians should be aware of the frequent occurrence of significant but transient biochemical hyperthyroidism associated with hCG stimulation in the early stages of gestation, particularly in twin pregnancies.
