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T Rabe

Publications and source records attributed to T Rabe.

118 records · Page 7Linked to original sources

Inhibition of human placental progesterone synthesis by aminoglutethimide in vitro.

Aminoglutethimide (AG) is an inhibitor of P-450 linked steroid hydroxylation reactions including the cholesterol side chain cleavage, which is the rate-limiting step by which the synthesis of pregnenolone and also progesterone can be controlled. d,1-AG is a weak inhibitor of the cholesterol side chain cleavage of human term placenta in vitro. The inhibitory potency of AG was greater in tests with mitochondrial preparations than in organ culture tests. The cholesterol side chain cleavage enzyme in mitochondria from a human term placenta showed a 10% residual activity in the presence of 300 microM AG. A 50% inhibition was obtained using 90 microM AG. Due to large unknown quantities of unlabeled cholesterol a Ki for AG could not be determined. In organ culture tests, the progesterone concentration in culture medium of a human term placenta decreased to 50% of control values with rising amounts of AG (3-300 microM) and increased to 60-70% of control values with higher AG concentrations (up to 3 mM). The slow AG-dose dependent decrease of progesterone in the incubation medium of early human pregnancy can be explained by an inhibition of progesterone degradation by means of hydroxylation. The increase of progesterone at higher AG (300-3000 microM) concentrations could be the result of the fact that degradation is inhibited more than progesterone is formed. AG (100 microM) showed no inhibition of mitochondrial 3 beta-hydroxysteroid dehydrogenase and cytoplasmic 20 alpha-hydroxysteroid dehydrogenase, both isolated from a human term placenta.

20-Hydroxysteroid Dehydrogenases↗

[Aminoglutethimide - a new drug for the after care in breast cancer].

Aminoglutethimide is an inhibitor of various steroid hydroxylation reactions in the adrenal gland, the ovary, the testis and the placenta; furthermore, the extraglandular estrogen synthesis is inhibited by blocking the aromatase in the subcutaneous fatty tissue.

Aminoglutethimide↗

New assays for the enzymatic conversion of cholesterol to pregnenolone.

Cholesterol side chain cleavage is determined by means of separation of (26-C14)-cholesterol and its radioactively labeled side chain (1-C14)k-isocaproic acid. Alumina minicolumn assay (AMCA): adsorption of cholesterol from an aqueous phase by aluminium oxide, while isocaproic acid can percolate through the column. In modification of a previously described technique (1), cholesterol is quantitatively eluted by ethanol. Filter assay (FA): retention of cholesterol by a membrane filter (pore size less than or equal to 0.1 um) while isocaproic acid can pass the filter. Two-phase scintillation assay (TPSA): pH-dependent partition of isocaproic acid between an organic scintillation mixture and an aqueous phase. The TPSA can be applied for all enzymatic reaction in which the polarity of the radioactive residue which is split off depends on pH values or when the total charge of a polar molecule is changed to an apolar state by cleaving one non-radioactive group (e.g. steroid sulfates) and vice versa. The criteria or reliability of the test systems are described. Bovine adrenal mitochondria were incubated and the side chain cleavage of (26-C14)-cholesterol was studied by the new tests systems and compared to the conversion rates of (4-C14)-cholesterol to its metabolites are determined by thin layer chromatography. A good agreement of all tests was found.

Aldehydes↗

Malaria in the highlands of Madagascar after five years of indoor house spraying of DDT.

The central region of Madagascar is a vast area of highlands (altitude 700-2000 m). Malaria transmission has re-established itself here since the last epidemic of 1985-90 and has caused the deaths of 40,000 persons according to the Minister of Health. To combat the main malaria vector in the region, Anopheles funestus, annual programmes of indoor house spraying of DDT were carried out between December 1993 and January 1998 in most rural areas at altitude 1000-1500 m. A parasitological and serological study was then conducted in the highland schools to evaluate the impact of the programme and set up a database on the region. Using a cluster-sampling method 2 independent selections were conducted (one of 130 sites, the other of 40 sites). During the study, 13,462 schoolchildren were examined, 71% living in sprayed villages. Parasite prevalence among schoolchildren declined as altitude increases, from 11% at 700-900 m to 0.4% at > 1500 m. Below 1500 m, the impact of the spraying on the prevalence of the parasite was very clear (an average decrease of from 20% to 2.7% below 1000 m and of from 4.5% without spraying to 0.8% at 1000-1500 m). Geographical analysis of the data showed that the marginal regions remained the most affected by malaria (especially outside spraying zones), and persistence of 'pockets of transmission' at 1000-1500 m, essentially in areas where spraying has never been used. In 9 schools, anti-Plasmodium antibodies were sought by indirect immunofluorescence on thick smears of parasitized red blood cells. The seroprevalence ranged from 22% to 63%, which suggests that the parasite is still circulating in the region. Even though our data show that vector control continues to be very successful in the Madagascan highlands, rapid reinfection could occur and must be monitored following spraying. To this end, the Minister for Health, with the support of the Italian Co-operation, has placed the region under epidemiological surveillance since 1997. An alert system for the timely detection of the sources of epidemics and the targeting of the antivectoral campaign is also in operation. Our study suggests that this strategy should be reinforced by the spraying of DDT in the marginal zones in order to consolidate the results obtained at higher altitudes.

Adolescent↗

[Malaria in Antananarivo: evaluation of a post-epidemic situation].

Antananarivo has a population of close to one million inhabitants and is located in the highlands of Madagascar. The capital was, until some years ago, thought to be a malaria transmission-free zone. However, between 1985 and 1990, several malaria cases occurred in the suburbs of Antananarivo, along the Ikopa river (the Betsimitatatra Plain), suggesting that local transmission was occurring. Numerous malaria cases have since been reported by health workers each year, but there is insufficient epidemiological information about the cause and origin of the transmission, because cases are rarely confirmed by parasitological examination. The National Malaria Control Management in Madagascar has, after four years of intensive DDT spraying campaigns in the highlands, stopped this specific method of control. Epidemiological follow-up studies will be carried out to evaluate the effects on malaria transmission of this cessation of control measures. The transmission of malaria in Antananarivo was studied from 1995 to 1996. Patients from nine health centers in various suburbs of Antananarivo were included in the study, with the presence of fever used as the sole inclusion criterion. Children randomly selected from schools in the same area were included in a second study group. A blood sample was obtained from each participant to determine the parasite index and the prevalence of antibodies against P. falciparum. The splenic index was also determined. A second assessment was performed for the school children six months later, using the same markers of malaria infection. Nine hundred and thirty two patients from the health center group were referred for participation in the study. This represented 10% of all patients and 74% of the patients with fever. The school group included 1,545 children. The splenic index was similarly low (0.5%) in the health center and school groups, as was the overall parasite index (2.6% for the health center group and 0.8% in the school group). The prevalence of antibodies against P. falciparum was also low, but with a seasonal variation: 2.5% in June 1995 and 11.6% in January 1996. Almost all the cases confirmed by parasitological examination were due to the patient having stayed in an area with hyperendemic malaria or having been in contact with an individual who had been to an area with a high level of transmission. Our findings confirm that Antananarivo is now in a post-epidemic situation. Malaria cases are mostly associated with a history of travel in areas with high levels of malaria transmission, particularly the coastal regions of Madagascar. Nevertheless, a low level of transmission may persist and lead to further outbreaks of malaria in the future, due to the presence in the area of Anopheles arabiensis.

Adolescent↗