214 research outputs found
Recognizing normal reproductive biology: A comparative analysis of variability in menstrual cycle biomarkers in German and Bolivian women
The idealized ānormalā menstrual cycle typically comprises a coordinated ebb and flow of hormones over a 28-day span with ovulation invariably shown at the midpoint. It's a pretty pictureābut rare. Systematic studies have debunked the myth that cycles occur regularly about every 28ādays. However, assumptions persist regarding the extent and normalcy of variation in other cycle biomarkers. The processes of judging which phenotypic variants are ānormalā is context dependent. In everyday life, normal is that which is most commonly seen. In biomedicine normal is often defined as an arbitrarily bounded portion of the phenotype's distribution about its statistical mean. Standards thus defined in one population are problematic when applied to other populations; population specific standards may also be suspect. Rather, recognizing normal female reproductive biology in diverse human populations requires specific knowledge of proximate mechanisms and functional context. Such efforts should be grounded in an empirical assessment of phenotypic variability. We tested hypotheses regarding cycle biomarker variability in women from a wealthy industrialized population (Germany) and a resource-limited rural agropastoral population (Bolivia). Ovulatory cycles in both samples displayed marked but nonetheless comparable variability in all cycle biomarkers and similar means/medians for cycle and phase lengths. Notably, cycle and phase lengths are poor predictors of mid-luteal progesterone concentrations. These patterns suggest that global and local statistical criteria for ānormalā cycles would be difficult to define. A more productive approach involves elucidating the causes of natural variation in ovarian cycling and its consequences for reproductive success and women's health
The Hypolipidemic and Anti-Inflammatory Activity of Boronated Aromatic Amino Acids in CF1 Male Mice
The boronated aromatic amino acids were shown to be potent hypolipidemic agents in mice lowering both
serum cholesterol and triglycerides after 16 days. Selective compounds were as effective as the clinical
standards. Furthermore, the compounds were effective anti-inflammatory agents reducing local and central pain
as well as suppressing LPS induced endotoxic shock in mice. These agents inhibited lysosomal and
proteolytic enzymes of the liver and macrophages as a part of their mechanism of action
The Synthesis and Antitumor Activity of the Sodium Salt and Copper (II) Complex of N-[(Trimethylamineboryl)-Carbonyl]-L-Phenylalanine Methyl Ester
Sodium N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine 2 and {N-[(trimethylamineboryl)-carbonyl]-L-phenylalanyl-
carbxylato}-bis-{N-[(trimethylaminebryl)-carbonyl]-L-phenylalanine} dicopper (II) 3 were
successfully synthesized. The agents blocked L1210 leukemic cell DNA and RNA syntheses by inhibiting
multiple enzyme activities for nucleic acid synthesis, e.g. PRPP amido transferase, IMP dehydrogenase, DNA
polymerase Ī±, thymidine kinase, and TMP kinase. The copper (II) complex 3 demonstrated improved ability
to inhibit L1210 partially purified DNA topoisomerase II compared to the parent compound while the sodium
salt was inactive at 100 Ī¼M
Cytotoxic Action of Carboxyborane Heterocyclic Amine Adducts
The heterocyclic carboxyborane amines were found to be potent cytotoxic agents in the murine L1210 lymphoid leukemia and human HeLa suspended carcinoma cells. These agents were observed to inhibit HeLa DNA topoisomerase II activity ~ 200 Ī¼M and L1210 topoisomerase II activity ā„ 100 Ī¼M. These agents did not cause DNA protein linked breaks themselves, but upon incubation for 14-24 hr did enhance the ability of VP-16 to cause cleavable complexes. The heterocyclic amineboranes inhibited DNA synthesis and caused DNA strand scission. They were additive with VP-16 in affording these results as well as inhibiting colony growth of L1210 cells after co-incubation for 1 hr. The agents inhibited in vitro PKC phosphorylation of both L1210 lymphoid leukemia and human topoisomerase II enzyme
The Pharmacological Activities of the Metabolites of N-[(Trimethylamineboryl)-Carbonyl]-L-Phenylalanine Methyl Ester
The metabolites of N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine methyl ester 1
proved to be active in a number of pharmacological screens where the parent had previously demonstrated potent activity. The proposed metabolites demonstrated significant activity as
cytotoxic, hypolipidemic, and anti-inflammatory agents. In cytotoxicity screens several of the
proposed metabolites afforded better activity than the parent compound against the growth of
suspended and solid tumor cell lines. Evaluation of in vivo hypolipidemic activity demonstrated
that the proposed metabolites of 1 were only moderately active and were generally less effective
than the parent compound. Interestingly, L-phenylalanine methyl ester hydrochloride 3, which
contains no boron atom, demonstrated equivalent hypolipidemic activity as the parent at 8
mg/kg/day in CF1 male mice. As anti-inflammatory agents the proposed metabolites
demonstrated variable capacities to reduce foot pad inflammation. These compounds were
similarly effective as the parent 1 at blocking local pain and were generally better than the parent
at protecting CF1 male mice from LPS induced sepsis
The Effects of Amine-Carboxyborane Related Derivatives on UMR-106 Bone Metabolism
The amine-carboxyboranes and related derivatives have been shown to be
potent anti-inflammatory and anti-osteoporosis agents. Their action in
part appears to be mediated by the modulation of cytokines, e.g. TNFĪ±
or IL-1. Previous studies have demonstrated that LPS induced
macrophages release of TNFĪ± maximally at 60 to 90 min. and IL-1 from 5
to 8 hr. The amine-carboxyboranes reduced significantly the release of
these cytokines but also blocked TNFĪ± high affinity binding to UMR-106
receptor at 90 min. at 10 Ī¼M, and IL-1 high affinity binding at 5 hr. at
12.5 Ī¼M. In addition, the agents suppressed IL-8 binding to CHO K1 high
affinity receptor at 24 hr. at 50 Ī¼M and IL-2 binding to HuT-8 receptors
at 25 Ī¼M at 90 min. and 5 hr. Correlation of metabolic events
associated with osteoporosis showed that at 90 min., when TNFĪ± receptor
binding was reduced by the agents, calcium uptake into UMR-106 cells was
reduced at 10 Ī¼M as well as the acid and alkaline phosphatases, and the
prostaglandin cyclo-oxygenase activities and adhesion of leukocytes and
macrophages to UMR-106 cell monolayers. At 5hr. when the agents reduced
IL-1 binding to UMR-106 receptors, calcitonin and 1,25-dihydrovitamin D3
binding was reduced by the agents as was acid and alkaline phosphatase,
and 5ā²-lipoxygenase activities and white blood cell adhesion. At this
time calcium uptake and proline incorporation was increased
significantly by the agents. At later times e.g. 18-48 hr. calcium
uptake was still increased, and NAG activity was inhibited in the
presence of the agents. These effects may be related more to the
inhibition of other cytokine receptor binding, e.g. IL-8. Thus, many of
the observed metabolic effects of amine-carboxyboranes as antiosteoporosis
agents can be correlated with their inhibition of cytokine
high affinity binding to target cell receptors
The Hypolipidemic Activity of Metal Complexes of Amine Carboxyboranes in Rodents
The metal complexes of amine-carboxyborane including copper, chromium, zinc, calcium amd cobalt were
effective hypolipidemic agents lowering both serum cholesterol and triglyceride levels significantly in mice at
8 mg/kg/day, I.P. after 16 days. The agents reduced acetyl CoA synthetase, ATP-dependent citrate lyase, acyl
CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase activities of rat liver and small
intestinal mucosa after 14 days treatment. The neutral cholesterol ester hydrolase activity was elevated by the
agents in both tissues. The metal complexes altered lipid levels in the bile of rats after treatment as well as
the bile acid composition after 14 days administration, orally. The agents blocked enterohepatic absorption of
cholesterol from rat isolated intestinal loops
- ā¦