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Biomedical subjects

G Scheffler

Publications and source records attributed to G Scheffler.

At least 19 recordsLinked to original sources
PubMed1996

Metabolism of reproductive steroids during the ovarian cycle in two species of callitrichids, Saguinus oedipus and Callithrix jacchus, and estimation of the ovulatory period from fecal steroids.

Gonadal steroids were measured in daily fecal samples providing comparative data on steroid metabolism in two genera of New World primates. Circulating bioactive LH and progesterone concentrations and fecal progesterone, pregnanediol, estradiol, and estrone concentrations were measured by collecting blood and daily fecal samples from four captive common marmoset females and four cotton-top tamarin females for 30 days. High recoveries (> 80%) of labeled steroids that were added directly to the feces before extraction were recovered from feces of both species. Because of the presence of complex steroid conjugates, only one fifth the amount of estradiol was measured without solvolysis as compared to the amount measured with solvolysis. In tamarins, steroids were metabolized rapidly, with all postovulatory increases occurring within two days after the circulating LH peak (an increase of 2 SD higher than mean follicular levels). In marmosets, steroid excretion was slower; increased steroid levels occurred 2-4 days after the LH peak except in the case of estrone, which did not consistently increase after the LH peak. Circulating estrone and estradiol both contributed to the high excretion of estradiol in the feces from both species. The timing in the delay in excretion of fecal steroids was used to accurately determine the ovulatory period to within a 2-day window. This degree of accuracy is possible when the duration of the delay to the LH peak is known for a given species. Additionally, steroid concentrations were highly correlated between frozen and lyophilized fecal samples (0.81 +/- 0.07 SEM), indicating that fluid removal from the feces did not effectively alter steroid profiles.

Animals↗
PubMed1995

The relationship of cortisol levels to social environment and reproductive functioning in female cotton-top tamarins, Saguinus oedipus.

Cortisol levels were examined in 17 cotton-top tamarin monkeys (Saguinus oedipus) to determine: (1) if first-morning void urine sampling could be used as a noninvasive method for monitoring cortisol excretion, (2) if capture and bleeding were associated with changes in urinary cortisol levels, (3) the relative cortisol levels in reproductively active and reproductively suppressed females, and (4) the relationship between cortisol levels and changes in social condition in cotton-top tamarins. Mean urinary cortisol levels during ovarian cycling did not differ between captured and bled females and undisturbed females. Mean cortisol levels were significantly lower in females who were housed in their natal groups and reproductively suppressed than in the same females when they were removed and placed adjacent to a novel male and ovarian cycling began. For all females, mean cortisol levels were higher during the periovulatory period than during the nonperiovulatory period of the ovulatory cycle, with mean cortisol levels higher in newly cycling females than in long-term cycling females. No differences were found in mean cortisol levels between long-term cycling females and prepubertal females and postpubertal natal females. Cortisol levels from long-term cycling females were much lower than during the first two to three ovarian cycles occurring in newly cycling female tamarins, during the last part of pregnancy, and during the first 6 weeks postpartum. These data provide evidence that (1) suppression of ovarian cycling in postpubertal females remaining in their natal family is not associated with stress-induced changes in cortisol levels, (2) cortisol levels are not strictly tied to reproductive condition, and (3) social change may be reflected in cortisol elevation.

Animals↗
PubMed1995

Synthesis and antitumor activity of two ifosfamide analogs with a five-membered ring.

Two ifosfamide (CAS 3778-73-2) analogs with a five-membered ring, i.e. the oxazaphospholidine derivatives 6 and 7, were synthesized and their cytotoxic activity in vitro, acute toxicity and antitumor activity in vivo determined in comparison with the oxazaphorinane ifosfamide 1. The observed low biological activity gives evidence that both, the six-membered oxazaphosphorinane ring and the two N-2-chloroethyl-side chains are necessary for the generation of the ultimate alkylator, i.e. the ifosfamide mustard 5.

Animals↗
PubMed1994

Behavioral effects of an antiandrogen in adult male rhesus macaques (Macaca mulatta).

This study was designed to determine how to suppress behavioral effects of androgens with a pure non-steroidal antiandrogen, Hydroxyflutamide (OHF). The major dependent variable was yawning behavior of castrated adult male rhesus macaques. Injections of testosterone propionate (TP) increased yawning frequency and cessation of TP injections produced a decrease in yawning frequency. A similar decrease was observed with simultaneous injections of TP and OHF. It has been found that the dose of OHF injected subcutaneously should be 80 times that of TP to block the effects of either physiological or supraphysiological doses of TP.

Androgen Antagonists↗
PubMed1994

Social and reproductive influences on plasma cortisol in female marmoset monkeys.

Subordinate female common marmosets (Callithrix jacchus) undergo ovulation suppression and exhibit low plasma cortisol levels compared to the dominant, breeding female. To determine whether this cortisol difference is mediated by the differential reproductive consequences of social status, we monitored plasma progesterone and cortisol in 32 adult female marmosets while they were housed in heterosexual pairs, during the first 3 days of heterosexual group formation, and while animals were housed in established social groups. Cortisol levels prior to group formation were significantly higher in females exhibiting cyclic ovulatory activity than in anovulatory females but were not predictive of social status. Subsequently, when animals were housed in established social groups, dominant (cyclic) females had significantly higher cortisol levels than did subordinate (anovulatory) females. Cortisol levels differed between the pre and postgroup formation conditions only in animals that underwent a corresponding onset or termination of ovulatory cyclicity. Cortisol differences between dominant and subordinate female marmosets therefore appear to be associated with differences in reproductive function rather than with social status per se.

Animals↗
PubMed1987

The endocrinology of puberty and reproductive functioning in female cotton-top tamarins (Saguinus oedipus) under varying social conditions.

Sexual maturation and fertility were assessed in fourteen cotton-top tamarin (Saguinus oedipus) females under various social conditions. Six tamarin females (20-28 mo of age) showed a suppression of fertility while living with their families. Hormonal profiles demonstrated low, acyclic levels of urinary luteinizing hormone (LH) and estrone-conjugates (E1C). A rapid onset of ovarian and pituitary cyclicity occurred when four of the six females were removed from their families and paired with an unrelated male. In one female, an ovulatory LH peak occurred as early as eight days after pairing and resulted in conception and full-term pregnancy. Two of the six females were housed in total isolation for 30 days following their removal from the family and prior to pairing. Gradual increases in hormone concentrations occurred during isolation; however, there was no ovarian cyclicity until each female was paired with an unrelated male. In all six females, conception occurred before or as a result of the third ovulatory cycle. Partial isolation of a 36-mo-old female resulted in elevated LH and E1C levels, but cyclicity was not observed until the female was paired with an unrelated male. These findings indicate that removal of a female from the family alone does not initiate ovarian cycling. Sexual maturation, or puberty, occurs in female tamarins living with their families between 15 and 17 mo of age when mean LH and E1C levels began to increase. However, when a female is removed and paired at 9 mo of age with an unrelated male, elevated levels of LH and E1C may be seen by 10 and 11 mo of age. Our findings indicate that a suppression of fertility occurs in cotton-top tamarins living with their families, but that reproductive suppression does not affect the process of sexual maturation. Both removal from the family environment and stimulation by an unrelated male tamarin were necessary to induce normal reproductive activity. An acceleration of puberty occurred when a female tamarin was removed from her family early in development and paired with a male.

Animals↗
PubMed1984

Chemical characterization of ASTA Z 7557 (INN mafosfamide, CIS-4-sulfoethylthio-cyclophosphamide), a stable derivative of 4-hydroxy-cyclophosphamide.

The primary metabolite of cyclophosphamide (CP, 1), i.e. 4-hydroxy-CP 2, has high pharmacological activity, but it is a very unstable compound. Chemical approaches to the stabilization involved in the substitution of the hydroxy group at the C 4-position, especially by a sulfoalkylthio-moiety. Within this new class of compounds ASTA Z 7557 (2-(bis-(2-chloroethyl]-amino-cis-4-[2-sulfoethyl)-thio)-tetrah ydr o-2H-1,3, 2-oxaza-phosphorine-r-2-oxide cyclohexylamine salt, i.e. cis-4-sulfoethylthio-CP, cis-13) was chosen for further evaluation. Cis-13 was synthesized by condensation of compound 2 and 2-mercapto-ethanesulfonic acid cyclohexylamine salt 14 in aqueous acetone yielding the cis-isomer with high stereoselectivity. It is a white crystalline powder, m.p. 126-134 degrees C, stable at room temperature, with a solubility of 16% in water. The stereochemistry was confirmed by NMR-data and X-ray diffraction. In 0.07 M phosphate buffer at pH 7 and 37 degrees C cis-13 isomerizes to the epimer trans-13, equilibrating at a cis-trans-ratio of 59 to 41 within less than 5 minutes. Simultaneously a rapid initial hydrolysis occurs to 2 and 14 followed by a time period with lower degradation due to the decomposition of 2. The rate of release of 2 increases with decreasing concentration and especially by addition of an oxidant. It could be retarded by addition of the corresponding thiol mesna, sodium 2-mercapto-ethanesulfonate 15, or of another thiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗
PubMed1983

Cyclic excretion of urinary oestrogens in female tamarins (Saguinus oedipus).

Urine was collected from 6 female cotton-top tamarins (Saguinus o. oedipus) and urinary oestrone and oestradiol concentrations were measured by radioimmunoassay. Oestrone was excreted at 50-fold higher concentrations than oestradiol. Five females showed patterns of regular oestrone cyclicity, with a mean peak-to-peak oestrone cycle of 23.6 +/- 1.2 days. Levels of oestradiol tended to vary with levels of oestrone excretion, but peaks were less pronounced and more variable. The sixth female, diagnosed as having 'wasting marmoset syndrome', had very low levels of excreted oestrogens, suggesting infertility. We suggest that urinary oestrone provides a good index to ovarian cyclicity in female cotton-top tamarins.

Animals↗
PubMed1983

[Synthesis of 14C-azelastine hydrochloride].

The synthesis of 4-(p-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone hydrochloride (14C-azelastine hydrochloride, Asta A 5610) is described Starting material was 14C-phthalic anhydride.

Carbon Radioisotopes↗
PubMed1982

[Synthesis and structure of new basic enol ethers].

Synthesis of new basic enol ethers with valuable pharmacological properties is described. The structure of these compounds is elucidated by 1H- and 13C-NMR-spectroscopy; the stereochemistry of the double bond is determined by use of the intramolecular nuclear Overhauser effect. An X-ray analysis of an isolated diastereomer confirms the proposed constitution.

Bridged-Ring Compounds↗
PubMed1982

[Synthesis of 4-ureidooxycyclophosphamide (author's transl)].

The synthesis of 4-ureidooxycyclophosphamide, a potential cytostatic, whose cis/trans-isomers can be stereoselectively obtained from 4-hydroxycyclophosphamide and hydroxyurea in DMF in DMF or water, is described. These compounds are remarkably stable at room temperature. For the first time, the two epimers from a derivative of 4-hydroxycyclophosphamide can be NMR-spectroscopically compared with each other.

Chemical Phenomena↗
PubMed1979

Effect of a low protein diet during pregnancy of the rhesus monkey. II. Physiological adaptation of the infant.

Heart rate, respiratory rate, and ability to maintain body temperature were evaluated in six infants born to rhesus monkeys that had been fed a low protein diet throughout pregnancy. All infants were kept in incubations equipped with a "servo" control thermal unit that maintained the infants' skin temperature at 37.0 C (98.6 F). The thermal units were disconnected and the infants were exposed to room temperature (approximately 27 C) for 6-hr periods each day after 24 hr of age in order to determine the efficiency of thermal control mechanism. The thermal servo control units were "on" for a longer period of time in experimental animals than in control animals during the first 24 hr of life. Infants from mothers fed the low protein diets were also less able to maintain their own body temperatures after exposure to room temperature. This function was seriously compromised in two of the six experimental infants. The compromised temperature control mechanism seen in these infant monkeys is a serious and potentially lethal side-effect of protein-calorie malnutrition during pregnancy. The possible relationship of inadequate maternal nutrition to the inefficient thermal mechanism of certain "high risk" human newborns should be reevaluated.

Adaptation, Physiological↗
PubMed1979

Acrolein, the causative factor of urotoxic side-effects of cyclophosphamide, ifosfamide, trofosfamide and sufosfamide.

The urotoxicity of oxazaphosphorine cytostatics is not based on their alkylating activity but on the presence of acrolein, which is spontaneously formed in the urine from the primary metabolites eliminated via the kidneys. Thus, acrolein proved to be the causative factor in the urotoxicity of oxazaphosphorines. The mechanism of action of the uroprotector sodium 2-mercaptoethane-sulfonate (mesnum, Mitexan) is mainly based on the formation of a non-toxic additive compound with acrolein.

Acrolein↗
PubMed1976

Mating in the rhesus monkey (Macaca mulatta) after conception and its relationship to oestradiol and progesterone levels throughout pregnancy.

Behavioural and hormonal data were collected throughout pregnancy in captive rhesus monkeys. Heterosexual pairs observed in daily time-limited mating tests showed two distinct periods of increased sexual interaction, as measured by the incidence of ejaculation. One period was coincident with the preovulatory oestradiol peak, while the other occurred between the 6th and 10th weeks of pregnancy. The positive relationship found during the menstrual cycle between the ratio of circulating oestradiol: progesterone and degree of sexual activity continued for the first 8 weeks of pregnancy. However, sexual activity ceased in the second half of pregnancy despite a continued high oestradiol: progesterone ratio.

Animals↗
PubMed1975

Multiple ejaculations during prolonged sexual tests and lack of resultant serum testosterone increases in Male Stumptail Macaques (M. arctoides).

The sexual behavior of four male and four female adult stumptail macaques was observed in standardized 3-hr heterosexual pair tests. The males achieved from 11 to 19 ejaculations during a single test, thus apparently exceeding any other primate studied under laboratory conditions for the ability to display multiple ejaculatory patterns in relatively short periods of time. The stage of the menstrual cycle was not found to be related to the performance of the male or female, although this variable was not analyzed in depth. Progressive increases in the interejaculatory interval (IEI) occurred for all four males for the initial two to four ejaculations of the series, and then either a plateau or a transient decrease in this measure occurred. Since the data varied considerably for IEI as well as for other quantitative measures of sexual behavior for a given pair, individual data rather than group averages are presented. Blood samples drawn immediately before and after behavioral testing as well as at comparable intervals 1 week prior to behavioral testing were analyzed for testosterone concentration by radioimmunoassay for each male. Serum testosterone values were not found to be influenced by multiple ejaculations. Instead, decreased levels of serum testosterone were encountered on the second blood sample of the day for most males, regardless of whether sexual behavior occurred. The possibility that the decreases were related to stress effects of handling is discussed. Because of this complication, it could be only tentatively concluded that repeated copulation to ejaculation over a 3-hr period did not result in appreciable changes in testosterone levels.

Animals↗