Stereocomplexes based on poly(lactic acid) and insulin: formulation and release studies.

Diastereoisomeric complexes of insulin with D-poly(lactic acid) (D-PLA) or stereocomplexes of D- and L-PLA entrapping insulin were discovered. The complexes were spontaneously formed when insulin and D-PLA were mixed together in acetonitrile solution. Complexes of insulin-D-PLA formed a microparticulate precipitate after a few hours in the solution. The porous 1-3 microm precipitate, which contained both insulin and D-PLA, was insoluble in solvents that dissolve isotactic PLA, and had an additional transition temperature at 169 degrees C. When suspending these particles in buffer solution of pH 7.4, 37 degrees C, insulin was constantly released for a few weeks. L-PLA or D,L-PLA did not form a precipitate with insulin, which indicates stereospecificity to the complex formation. Microparticulates were also obtained when L-PLA was added to the D-PLA-insulin solution. In this case two types of complexes, D-PLA-insulin and D-PLA-L-PLA complexes, were formed. These macromolecular stereocomplexes may form the onset of the development of a new generation of controlled release systems for peptides and proteins, by molecular complexation with enantiomeric polymers.

Midwifery co-management of hyperemesis gravidarum.

Hyperemesis gravidarum is an infrequent, yet significant, maternal complication of pregnancy. Beginning with the frequently experienced nausea and vomiting of pregnancy, symptoms can progress to hyperemesis, a debilitating condition affecting maternal and fetal well-being. A basic understanding of the pathophysiology of the disease process and an awareness of the therapeutic interventions that are available will facilitate midwifery planning for either the collaborative care or the potential referral to medical management, both of which may be required with this clinical entity. The diagnosis and initial management of hyperemesis is within the purview of midwifery care. As certain critical features of duration and severity evolve, medical collaboration and ultimate hospitalization may be required. For those few individuals requiring the most intense level of care, the critical support and encouragement afforded by midwifery participation will contribute to timely resolution of this debilitating condition. This article discusses the continuum from differential diagnosis to ultimate care of the woman who has excessive nausea and vomiting of pregnancy. Collaboration among health care providers will allow all to exercise their respective skills in achieving the optimum in safe therapy and support for their patients.

Scope of practice: freedom within limits.

"Scope of practice" has a variety of meanings amongst midwives, other health professionals, health organizations, and consumers of midwifery care. For some, it refers to the Standards for the Practice of Midwifery; for others, it encompasses the legal base of practice; still others equate it with the components of the clinical parameters of practice. Because "scope of practice" is dynamic and parameters of practice can be impacted by many variables, succinctly defining "scope of practice" is difficult. This article provides a comprehensive discussion of the concept "scope of practice." Clinical scenarios are provided as case exemplars. The aim of this paper is to provide both new and experienced midwives with a substantive definition of the concept "scope of practice."

Structural requirements for binding of anandamide-type compounds to the brain cannabinoid receptor.

In order to establish the structural requirements for binding to the brain cannabinoid receptor (CB1), we have synthesized numerous fatty acid amides, ethanolamides, and some related simple derivatives and have determined their Ki values. A few alpha-methyl- or alpha, alpha-dimethylarachidonoylalkylamides were also examined. In the 20:4, n-6 series, the unsubstituted amide is inactive; N-monoalkylation, at least up to a branched pentyl group, leads to significant binding. N,N-Dialkylation, with or without hydroxylation on one of the alkyl groups, leads to elimination of activity. Hydroxylation of the N-monoalkyl group at the omega carbon atom retains activity. In the 20x, n-6 series, x has to be either 3 or 4; the presence of only two double bonds leads to inactivation. In the n-3 series, the limited data reported suggest that the derived ethanolamides are either inactive or less active than comparable compounds in the n-6 series. Alkylation or dialkylation of the alpha carbon adjacent to the carbonyl group retains the level of binding in the case of anandamide (compounds 48, 49); however, alpha-monomethylation or alpha,alpha-dimethylation of N-propyl derivatives (50-53) potentiates binding and leads to the most active compounds seen in the present work (Ki values of 6.9 +/- 0.7 to 8.4 +/- 1.1 nM). We have confirmed that the presence of a chiral center on the N-alkyl substituent may lead to enantiomers which differ in their levels of binding (compounds 54, 57 and 55, 56).