Timing between ejaculations changes paternity success

It is believed that when two male rats copulate with a single female, the last one that ejaculates fathers significantly more pups than the first one. To determine the effects of order and elapsed time between two males copulating with the same female, albino Wistar (W) and pigmented Long-Evans (LE) male rats copulated with a W female. Paternity was confirmed by the pups' pigmentation. Three groups were made according to the elapsed time between the first male's ejaculation and the placement of the female with the second male; T0 (0-min group); T5 (5-min group); and T10 (10-min group). Male order was counterbalanced in each group. The results showed that the second male had the advantage in T0, but the first males had the advantage in T5 and T10. These data indicate that in a two-male situation, the advantage in paternity for a second male occurs only during copulations following the first few minutes of a first male's ejaculation. After 5 min, a second male has no advantage in fathering pups.     

HLA class II molecules on monocytes regulate T cell proliferation through physical interaction in the CD3 activation pathway

HLA class II molecules are involved in the OKT3-induced T cell activation, since monoclonal antibodies (mAb) to monomorphic determinants of class II antigens are able to inhibit T cell proliferation. This effect involves several of the events leading to T cell activation and proliferation, i.e. interleukin (IL) 1, IL 6 and IL2 secretion and IL2 receptor expression. The main target of the inhibition is represented by monocytes, and the interference of anti-class II mAb in the direct interaction of monocytes with T cells is likely to play a relevant role in the inhibition mechanism. To test this hypothesis, we investigated in the present study the effect of anti-class II mAb on the proliferation of T cells stimulated with mAb OKT3 in the presence of paraformaldehyde-treated monocytes. We show that the inhibition of proliferation is specific and dose dependent, and seems to involve particular class II epitopes. Addition of fixed monocytes to inhibited T cell cultures restores proliferation to a moderate extent, only if monocytes are added within the first 12 h of culture, suggesting that class II antigens or spatially related molecules deliver signals concurrently with the mitogenic stimulus. The blocking capability of anti-class II mAb was not restricted to the CD4+ or the CD8+ T cell subsets, suggesting that, under inhibitory conditions, these mAb affect other structures on the T cell surface, relevant to the monocyte-T cell interaction.     

Olfactory conditioned partner preference in the female rat

Paced copulation induces conditioned place preference in female rats. The authors examined whether associating almond-scented males with paced copulation induces conditioned partner preference. The paired group received 4 paced copulations with almond-scented males and 4 nonpaced copulations with unscented males sequentially at 4-day intervals. The unpaired group received the opposite order of association, whereas the randomly paired group received random associations. A 4th group received a single pairing. On the final test, females were placed into an open field with 2 males, 1 scented and 1 unscented. Females in the paired group solicited the scented male more frequently, and most chose the scented male for their 1st ejaculation. Thus, an odor paired with paced copulation elicits conditioned partner preference in female rats.     

CD40 expressed on human melanoma cells mediates T cell co-stimulation and tumor cell growth

CD40 is a 50 kDa molecule, a member of the tumor necrosis factor/nerve growth factor receptor family. It is expressed on B cells, monocytes, dendritic cells and various malignant cells. While the critical relevance of this molecule in T cell-dependent B cell activation is already established, the biological role of CD40-CD154 interaction in non-hematopoietic cells is still unknown. Here we show that CD40 is functionally expressed on human melanoma-derived cell lines. No correlation between surface CD40 expression and the origin of the cell line, primary versus metastatic, was observed. Melanoma cells were shown to be able to co-stimulate TCR-triggered human T cells; moreover, because they do not express CD80 or CD86 co-stimulatory structures, the involvement of additional pathways have to be postulated. We have identified CD40 as one of the molecules involved in melanoma cell-mediated co-stimulation of anti-CD3-triggered human CD4(+) T lymphocytes. In addition, a CD40-dependent pathway, able to enhance tumor cell proliferation at low serum concentrations, in vitro, has been shown to be functional in human melanoma cell lines.     

Back to the future: identification and classification of polymyalgia rheumatica and polymyalgia rheumatica-like syndromes following cancer immunotherapy with checkpoint inhibitors

Polymyalgia rheumatica (PMR) and PMR-like syndromes are among the most frequent rheumatologic immuno-related adverse events (IRAEs) induced by cancer immunotherapy with “checkpoint inhibitors” (ICIs). Our short communication addresses two key methodological issues laid bare by published literature : 1) how to diagnose PMR and PMR-like syndromes following ICI therapy, 2) how PMR/PMR-like syndromes following ICI therapy are described as adverse drug reactions (ADRs).     

Morgagni-Larrey diaphragmatic hernia: report of a case

The Authors presents a Morgagni-Larrey's diaphragmatic hernia case, observed during subocclusive manifestation. They emphasize the utility to perform always the surgical intervention, also in the asintomatic cases.     

Characterization of the Solubility and Solid-State Properties of Saccharin Salts of Fluoroquinolones

Saccharinates salts of the fluoroquinolone antibiotics norfloxacin, ciprofloxacin, ofloxacin, and enrofloxacin were obtained as pure crystalline anhydrous solids with sweet taste. The products were characterized by one- (¹³C) and two-dimensional (¹H–¹³C) dimensions solid state Nuclear Magnetic Resonance and infrared spectroscopy showing ionic interactions between the saccharine amide and the fluoroquinolone piperazine. Several intermolecular bindings were also identified. Thermal behavior and powder X-ray diffraction provided complementary evidences of salt formation. The series of products showed improved properties with respect to water solubility. A solubility model was developed. These salts would be a good way forward to developing more suitable formulations of these APIs. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3788–3801, 2009