Comparison of radioimmunoassay and gas-liquid chromatography analyses of progesterone concentrations in cow's milk.

Progesterone concentrations in milk were not significantly different when quantitated by different methods (RIA vs. GLC). There was a significant day effect (P less than 0.05) on milk progesterone level due apparently to gradually decreasing values as pregnancy advanced over days 30, 120 and 210. The means for the percent fat content were different (P less than 0.05) for all comparisons among four times of collection (immediately premilking, milking pool, immediately postmilking, and 3 hr postmilking). For progesterone concentration, the main effect of time and the three-way interaction (time times antiserum times purification method) were significant (P less than 0.005); all other main effects and interactions were not significant. Within each of 4 assay groups (2 antisera times 2 purifications), the concentration of progesterone was greater (P less than 0.05) for the samples which were collected immediately postmilking than for any of the other times of collection. The three-way interaction seemed due primarily to difference in progesterone determinations among the four assay groups in the samples which were taken immediately postmilking. Over all milk samples within each assay group, the percent fat content and the concentration of progesterone were positively correlated (r = 0.71, P less than 0.01).     

Nusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response.     

Ciclo di Accrescimento E Differenziazione Delle Gemme in Piante Perenni Nel Territorio di Bari

Summary

Growth cycle and buds differentiation in perennial plants growing in Bari's area. — V. The evolution of the wood ring in Rhammus Alaternus L. from December 1946 to March 1949.

In Rhamnus Alaternus L. the cambium awackens in March with the production of an early wood, characterized by large vessels and loose fibers. It keeps on dividing the following months, producing intermediary wood, whose vessels become narrower and narrower. In June the wood ring is almost complete and the cambial activity slows down. In July late wood is formed, with narrow tracheae and highly lignified fibers. From August to February cambial activity is very scarce and irregular, in the wood produced fibers being tangentially compressed.

In a young branch of R. A. cambium becomes suddenly active in February, that is one month before than in the stem, it goes on during the month of March-June, with an evident diminution in the size of the wood elements. This diminution of size instead of being regular, shows some oscillations, expecially during the month of May. In Sept. the cambium starts again dividing, but rather poorly and irregularly, forming some vessels a little wider than the preceeding ones, so that an incomplete false ring is formed only in some points of the branch. As a rule the autumn wood is a typical late wood. This scarce and irregular cambial activity goes on also during Oct.-Dec. In January is more active and forms rather wide vessels in comparison with those formed in the preceeding month. This new formed wood however does not show the characteristics of the early wood of a new ring.

Concluding, the characteristics of the cambial activity of A. R. are

In the stem: 1) March: early wood. 2) March-June: intermediary wood. 3) July: late wood, resting period. 4) At the end of Autumn a scarce production of late wood is sometimes possible.

In the young branch: 1) February: early wood. 2) March-June: intermediary wood, with positive and negative oscillations in the vessels width. 3) At the end of June the late wood is already differentiated. 4) July-August: resting period. 5) Spt.-Juan.: the cambium starts again dividing very scarcely and producing a transition wood between the two rings. This wood can be regarded neither as a true ring nor a false one, it represents rather the last phase of the late wood formation. 6) In the young branch of the female specimen the cambium starts dividing somewhat later than in the male one. 7) The wood ring width does not vary much in relation to the yearly amount of rainfall. The lack of relation between rainfall and ring width is particularly evident in 1948 (a rainy year). The, «Compleasance» of R. A. could show that this species is, in Puglia, in its own habitat. On the other hand it is rather peculiar that R. A. forms only one wood ring during one year, with production of early wood during the spring, and of late wood in the autumn, instead of producing a second autumn ring following a distint summer rest, as could be expected.     

Design,synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives

Abstract

A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in?vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC₅₀ values in the µM range. In addition, the in?vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.     

Bisphenol-A Impairs Insulin Action and Up-Regulates Inflammatory Pathways in Human Subcutaneous Adipocytes and 3T3-L1 Cells

Current evidence indicates that chemical pollutants may interfere with the homeostatic control of nutrient metabolism, thereby contributing to the increased prevalence of metabolic disorders. Bisphenol-A (BPA) is a lipophilic compound contained in plastic which is considered a candidate for impairing energy and glucose metabolism. We have investigated the impact of low doses of BPA on adipocyte metabolic functions. Human adipocytes derived from subcutaneous adipose tissue and differentiated 3T3-L1 cells were incubated with BPA, in order to evaluate the effect on glucose utilization, insulin sensitivity and cytokine secretion. Treatment with 1nM BPA significantly inhibited insulin-stimulated glucose utilization, without grossly interfering with adipocyte differentiation. Accordingly, mRNA levels of the adipogenic markers PPARγ and GLUT4 were unchanged upon BPA exposure. BPA treatment also impaired insulin-activated receptor phosphorylation and signaling. Moreover, adipocyte incubation with BPA was accompanied by increased release of IL-6 and IFN-γ, as assessed by multiplex ELISA assays, and by activation of JNK, STAT3 and NFkB pathways. Treatment of the cells with the JNK inhibitor SP600125 almost fully reverted BPA effect on insulin signaling and glucose utilization. In conclusion, low doses of BPA interfere with inflammatory/insulin signaling pathways, leading to impairment of adipose cell function.