Disruption of maternal behavior by alcohol intoxication in the lactating rat: a behavioral and metabolic analysis

BACKGROUND: Preweanling rats exhibit clear behavioral signs of distress after interacting with an alcohol-intoxicated dam. Interestingly, behavioral reactivity of infants to the experience of alcohol in the nursing context decreases as a function of repeated alcohol administrations to the mother. In this study, maternal activities were examined when dams were exposed to repeated administrations of a subnarcoleptic alcohol dose. Maternal changes in alcohol metabolism were also analyzed as a function of repeated exposures to the drug. METHODS: During postpartum days 3, 5, 7, 9, 11, and 13, nursing dams received an intragastric administration of either 2.5 g/kg of alcohol or water. Maternal behaviors were evaluated (experiment 1). Blood alcohol levels (BALs) of the dams were determined on postpartum day 16 after all mothers received either an intragastric (experiment 2) or an intraperitoneal (experiment 3) dose of alcohol. The doses used (2.5 g/kg intragastrically and 1.5 g/kg intraperitoneally) were chosen because they promote similar peak BALs in dams naive to alcohol. RESULTS: Maternal behaviors were strongly affected by the state of intoxication. Nevertheless, these disruptions clearly subsided with progression of alcohol-related experiences (experiment 1). Chromatographic analysis of alcohol metabolism indicated the development of tolerance in dams that had prior experience with alcohol (experiment 2). Changes in BALs as a function of prior experience with alcohol seemed related to first-pass alcohol metabolism rather than hepatic oxidative processes of the drug (experiments 2 and 3). CONCLUSIONS: When the dam first experiences a moderate state of alcohol intoxication, maternal behaviors are uniformly disrupted. Subsequent exposures to alcohol lead to maternal metabolic tolerance. In conjunction with previous studies, these data indicate that infantile reactivity to alcohol is dependent on how the members of the dam/pup dyad express or perceive ethanol's postabsorptive effects.     

An outwardly rectifying anion channel in human leukaemic K562 cells

In this study, an outwardly rectifying anion channel was characterized in the cell line K562 obtained from a chronic human leukaemia. Ion channel activity was recorded in the cell-detached (inside-out) configuration with standard patch-clamp technology. In most of the K562 cells studied, the channel exhibited low spontaneous activity, an outwardly rectifying current/voltage relationship and single-channel conductances of 19 pS and 40 pS for inwards and outwards currents respectively. The channel had a low permeability for gluconate with a relative permeability P(gluconate)/ P(Cl) of 0.14 and was blocked by glibenclamide (50 micro M) or diphenylamine-2-carboxylate (DPC, 1 mM) added to the cytoplasmic side of the patch. These results are characteristic of the outwardly rectifying Cl channel (ORCC) found in other types of cells.     

Deoxycorticosterone stimulates the activity of nicotinamide adenine dinucleotide phosphate-diaphorase/nitric oxide synthase immunoreactivity in hypothalamic nuclei of rats

Mineralocorticoids (MC) play an important role in development of salt appetite. Part of this effect involves the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, in which MC treatment increases arginine vasopressin (AVP) synthesis and release. Since the AVP system is also modulated by nitric oxide (NO), we studied if deoxycorticosterone acetate (DOCA) treatment changed the number of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) active neurons and neuronal NO synthase (nNOS)-immunoreactive (IR) cells in the PVN and SON. After four injections of DOCA (10 mg/rat per day), rats developed a salt appetite and increased NADPH-d active and nNOS-IR neurons in both nuclei. A single DOCA injection did not change salt consumption or nNOS-IR cells, but increased the number of NADPH-d positive neurons in the PVN only. Therefore, while acute MC treatment stimulated the activity of pre-existing enzyme, chronic steroid treatment recruited additional neurons showing nNOS immunoreactivity/NADPH-d activity. These data suggest a role for NO produced in the PVN and SON in DOCA stimulatory effects on AVP mRNA and salt appetite.     

Peripheral lymphadenopathy as the initial manifestation of pericardial mesothelioma: a case report

Lymphadenopathy is an unusual initial presentation of malignant mesothelioma. We describe a case of extrathoracic lymphadenopathy as the only initial manifestation of primary pericardial malignant mesothelioma. The diagnosis of metastatic malignant mesothelioma was made by excisional biopsy of the supraclavicular lymph node and later confirmed by cytologic examination of pericardial fluid. The clinical and pathological features of this case, including positron-emission tomography (PET), immunohistochemistry, and electron microscopy, are discussed.     

Design,synthesis and cytotoxic evaluation of a library of oxadiazole-containing hybrids

The development of hybrid compounds led to the discovery of new pharmacologically active agents for some of the most critical diseases, including cancer. Herein, we describe a new series of oxadiazole-containing structures designed by a molecular hybridization approach. Penicillin derivatives and amino acids were linked to amino acid and aromatic moieties through the formation of a 1,2,4-oxadiazole ring. Alternatively, condensation between amino acid-derived hydrazides and an activated penicillanic acid led to a series of 1,3,4-oxadiazole penicillin-containing hybrids and non-cyclized diacylhydrazides. From the cytotoxicity assays it is highlighted that two 1,2,4-oxadiazoles and one 1,3,4-oxadiazole connecting a penicillin and aliphatic amino acids displayed a high degree of cytotoxic selectivity, ranging between being three and four times more potent against tumor cells than normal cells. The results give a very interesting perspective suggesting that these hybrid compounds can offer a novel antitumor scaffold with promising cytotoxicity profiles.

Synthesized hybrids of 1,2,4-oxadiazole and 1,3,4-oxadiazole connecting a penicillin and aliphatic amino acids displayed a high degree of cytotoxic selectivity.     

Polyfluoroalkylated antipyrines in Pd-catalyzed transformations

In the direct C–H arylation with arylhalogenides in the presence of Pd(OAc)₂, trifluoromethyl-containing antipyrine reacts very slowly and incompletely owing to the low nucleophilicity of its C4 center. However, it was effective in modifying polyfluoroalkyl-substituted 4-bromo- and 4-iodo antipyrines by the Suzuki and Sonogashira reactions. It was established that using Pd₂(dba)₃ as catalyst and XPhos as phosphine ligand was the optimal catalytic system for the synthesis of 4-aryl- and 4-phenylethynyl-3-polyfluoroalkyl-antipyrines. Moreover, iodo-derivatives as the initial reagents were found to be more advantageous compared to bromo-containing analogs. It was found that 4-phenylethynyl-5-CF₃-antipyrine has a moderate activity against the influenza virus A/Puerto Rico/8/34 (H1N1) and 4-iodo-5-CF₃-antipyrine reveals a weak activity against the vaccine virus (strain Copenhagen) and bovine diarrhea virus (strain VC-1).

Peculiarities of heterocyclic systems with electron-withdrawing groups (polyfluoroalkyl-containing antipyrines) in Pd-catalyzed C–H arylation and cross-coupling reactions.     

Neurotransmitter imbalance in serum of psoriatic patients in exacerbation stage with comorbid psychoemotional disorders

The role of psychological factors in the manifestation and exacerbation of psoriasis is well known. Acute and chronic stress, anxiety, and depression affect the reactions of innate and acquired immunity. The exacerbations of psoriatic lesions are accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. The role of inhibitory neurotransmitters in the serum of patients with psoriasis exacerbation with comorbid emotional disorders is assessed. Forty patients with psoriasis in the exacerbation stage were examined. Spielberger State‐Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI) scale were used to assess anxiety and depression parameters. We also evaluated the concentration of serotonin and gamma‐aminobutyric acid (GABA) in the serum. Patients with psoriasis had significant anxiety and depressive disorders. An imbalance in serotonin levels and a decrease in serum GABA levels in patients with psoriasis in the acute stage were noted. Only patients with anxiety disorder had increased serotonin levels. Our findings suggest that the imbalance of neurotransmitters in patients with psoriasis in the acute stage is important in predicting the development of the emotional well‐being.     

Secondary lymphoid tissue chemokine (CCL21) is upregulated in allergic contact dermatitis

Chemokines are important players in the development of allergic contact dermatitis (ACD). The participation of secondary lymphoid tissue chemokine (CCL21) is essential in the induction of the disease due to its expression in lymphatic vessels and in secondary lymphoid organs. Since there is no information about its participation during the effector phase of ACD, we studied this chemokine in patients already diagnosed with ACD, who were challenged with the relevant positive and negative (control) antigens. All patients showed a specific antigen-induced immune response characterized by early expression of inflammatory markers in blood endothelial cells followed by dermal accumulation of mononuclear cells with an important increase in infiltration of CXCR3+ but not of CCR7+ cells. In situ hybridization and immunohistochemistry showed low levels of CCL21 in lymphatic vessels at 2 h, whereas they were significantly increased at 10 and 48 h in all positive patch tests. In contrast, very low expression of this chemokine was observed in skin biopsies from the control site at 48 h. In addition, Langerin+ cells, which were present in dermis from positive patch tests at 2 h, were diminished in number at 10 and 48 h, but a significant number of those cells was still present in dermal areas of the control site at 48 h. We demonstrate for the first time that CCL21, a constitutively expressed chemokine, is strongly upregulated in human lymphatic vessels during a Th1/Tc1 allergic inflammatory response. This can provide the signal required for CCR7+ cells to leave the skin through CCL21-positive lymphatic vessels.