Pre-Clinical and Clinical Pharmacology of 17alpha-Hydroxyprogesterone caproate (17-OHPC): An Agent for the Prevention of Preterm Birth.

Preterm birth (PTB), birth prior to 37 weeks of gestational age, is a major cause of early childhood mortality and morbidity in the United States. 17alpha-hydroxyprogesterone caproate (17-OHPC) has recently been documented to reduce the incidence of preterm birth. A complete understanding of the pharmacokinetics of 17-OHPC will help in improving clinical outcome. The goal of this dissertation research was to evaluate the preclinical and clinical pharmacology of 17-OHPC in order to optimize the use of this drug in preventing preterm birth.Studies in human liver microsomes and human hepatocytes indicate that 17-OHPC is metabolized by CYP3A. Significant transplacental transfer of 17-OHPC (cord blood to maternal plasma ratio of 0.3) has been observed in pregnant subjects. Studies were performed in fetal hepatocytes to evaluate the metabolism of 17-OHPC. Fetal hepatocytes demonstrate the ability of human fetal liver to metabolize 17-OHPC to fetal specific metabolites, with oxidation being the major metabolic pathway. Further, 17-OHPC and/or its metabolites inhibit bile salt transport in both adult and fetal hepatocytes. To understand the clinical pharmacology of 17-OHPC, pregnant women who received 17-OHPC for clinical reasons were studied and blood samples collected periodically. Wide-interindividual variation was observed in the pharmacokinetics of 17-OHPC in pregnant subjects. The half life of 17-OHPC was 9 days and plasma concentrations of 17-OHPC did not achieve steady state. The race and body mass index of the pregnant subjects affect the plasma levels of 17-OHPC. In conclusion, since CYP3A is involved in the oxidative metabolism of numerous commonly used drugs; 17-OHPC may be involved in clinically relevant metabolic drug interactions with co-administered CYP3A inhibitors or inducers. Since 17-OHPC crosses the placental barrier and reaches the fetus, use of higher doses of 17-OHPC should be approached with caution. The clinical effectiveness of 17-OHPC in preventing preterm birth has been observed in only 33% of the patients. Given the wide interindividual variability, modification of the starting dose based on BMI and race alongwith monitoring of plasma levels and adjustment of subsequent doses accordingly may be needed to improve therapeutic outcomes in the treatment of preterm birth with 17-OHPC

Pharmacokinetics of 17-hydroxyprogesterone caproate in multifetal gestation

To define the pharmacokinetic (PK) parameters of 17-hydroxyprogesterone caproate (17-OHPC) in multifetal gestation

A STUDY OF ANISOTROPIC MAGNETORESISTANCE IN A-FENIMNBSI ALLOYS

Longitudinal and transverse magnetoresistivity measurements have been performed on a-Fe40-xNi40MnxB12Si8 alloys (0 less-than-or-equal-to x less-than-or-equal-to 5.5) in fields up to 40 kG, at 4.2 K, 100 K, 200 K, and 300 K. Above technical saturation, all the alloys exhibit a negative slope, i.e. the resistivity decreases as a function of the magnetic field. The high-field magnetoresistivity slope becomes more and more negative with increasing Mn concentration. Assuming that the negative slope of magnetoresistance is caused by the suppression of spin waves, the temperature and composition dependence of magnetoresistivity of the present series could be qualitatively understood. The spin-wave contribution to the zero-field resistivity has been estimated using a simplified approach. Furthermore, the ferromagnetic anisotropy of resistivity (FAR) has been calculated and the results are analysed in the light of a two-current conduction model generalized to weak ferromagnets and amorphous alloys

The enhancement of fe hyperfine field with mn addition in A-FE(80-X-Y)NIYMNXB12SI8 alloys

Amorphous Fe(80-x-y)Ni(y)Mn(x)B12Si8 alloys with 0 less-than-or-equal-to x less-than-or-equal-to 1 and 20 less-than-or-equal-to y less-than-or-equal-to 50, have been studied using Mossbauer spectroscopy at 77 K. It has been found that the sharp rise in the alloy magnetic moment for certain specific values of x and y can be best explained if both mu-Fe and mu-Ni increase for those particular samples. However, the increase in mu-Ni (approximately 80%) is much larger than that in mu-Fe (approximately 5%)

Temporal variations in patterns of Escherichia coli strain diversity and antimicrobial resistance in the migrant Egyptian vulture

Aims: Multiple antimicrobial resistance in Escherichia coli of wild vertebrates is a global concern with scarce assessments on the subject from developing countries that have high human-wild species interactions. We studied the ecology of E. coli in a wintering population of Egyptian Vultures in India to understand temporal changes in both E. coli strains and patterns of antimicrobial resistance. Methods and Results: We ribotyped E. coli strains and assessed antimicrobial resistance from wintering vultures at a highly synanthropic carcass dump in north-west India. Both E. coli occurence (90.32%) and resistance to multiple antimicrobials (71.43%) were very high. Clear temporal patterns were apparent. Diversity of strains changed and homogenized at the end of the Vultures’ wintering period, while the resistance pattern showed significantly difference inter-annually, as well as between arrival and departing individuals within a wintering cycle. Significance of study: The carcass dump environment altered both E. coli strains and multiple antimicrobial resistance in migratory Egyptian Vultures within a season. Long-distance migratory species could therefore disseminate resistant E. coli strains across broad geographical scales rendering regional mitigation strategies to control multiple antimicrobial resistance in bacteria ineffective

EFFECT OF MN AND NI ON THE ELECTRICAL-RESISTIVITY OF AMORPHOUS FE(80-X-Y)NIYMNXB12SI8 ALLOYS

Electrical resistivity studies have been carried out on a-Fe(80-x-y)NiyMnxB12Si8 alloys (0 100 K). In the Mn containing alloys, however, we do not find evidence for the presence of two such terms of opposite signs. It was also found that the presence of Ni increases the positive temperature coefficient of resistivity, but the increase was stronger in Mn containing alloys