Stressful stimuli during pregnancy induce complex effects that influence the development of offspring. These effects can be prevented by environmental manipulations during the early postnatal period. Repeated restraint during the last week of pregnancy was used as a model of prenatal stress, and adoption at birth was used to change the postnatal environment. No differences were found in various physical landmarks, except for testis descent, for which all prenatally stressed pups showed a 1-day delay in comparison with control rats, regardless of the postnatal adoption procedure. Levels of dopamine (DA) D(2) and glutamate (Glu) N-methyl-D-aspartate (NMDA) receptors were differentially regulated in different forebrain regions of cross-fostered adult offspring. Increased concentrations of cortical D(2) receptors detected in stressed pups, raised by a gestationally stressed biological mother, were not detected when the pups were raised by a control mother. Control pups raised by a foster mother whether gestationally stressed or not had higher levels of NMDA receptors in cortical areas. These findings suggest that the normal expression of DA and Glu receptors is influenced by in utero experience and by lactation. The complex pattern of receptor changes reflects the high vulnerability of DA and Glu systems to variations both in prenatal and in postnatal environment, particularly for cortical D(2) receptors and NMDA receptors in cerebral cortex and nucleus accumbens. In contrast, testis descent appears to be more susceptible to prenatal than to postnatal environmental events.

Objectives: To assess the epidemiological features of 76 KPC producing K. pneumoniae isolates (KPC-Kp) recovered in 3 hospitals of Buenos Aires, Argentina, during 2015-2017. Methods: Antimicrobial susceptibilities were determined according to CLSI. Molecular typing of KPC-Kp was performed by PFGE-XbaI and MLST. Plasmid encoded genes involved in carbapenem, fosfomycin and colistin resistance were detected by PCR and sequencing. Also mgrB inactivation was investigated in those colistin resistance isolates. Genetic platforms involved in horizontal spread of bla KPC were investigated by PCR mapping.Results: Besides β-lactams, high resistance rates were observed for gentamycin, quinolones and trimethoprim-sulfamethoxazole. KPC-Kp ST258 corresponded to

Prenatal stress greatly influences the ability of an individual to manage stressful events in adulthood. Such vulnerability may result from abnormalities in the development and integration of forebrain dopaminergic and glutamatergic projections during the prenatal period. In this study, we assessed the effects of prenatal stress on the expression of selective dopamine and glutamate receptor subtypes in the adult offsprings of rats subjected to repeated restraint stress during the last week of pregnancy. Dopamine D2-like receptors increased in dorsal frontal cortex (DFC), medial prefrontal cortex (MPC), hippocampal CA1 region and core region of nucleus accumbens (NAc) of prenatally stressed rats compared to control subjects. Glutamate NMDA receptors increased in MPC, DFC, hippocampal CA1, medial caudate-putamen, as well as in shell and core regions of NAc. Group III metabotropic glutamate receptors increased in MPC and DFC of prenatally stressed rats, but remained unchanged in all other regions examined. These results indicate that stress suffered during the gestational period has long lasting effects that extend into the adulthood of prenatally stressed offsprings. Changes in dopamine and glutamate receptor subtype levels in different forebrain regions of adult rats suggest that the development and formation of the corticostriatal and corticolimbic pathways may be permanently altered as a result of stress suffered prenatally. Maldevelopment of these pathways may provide a neurobiological substrate for the development of schizophrenia and other idiopathic psychotic disorders.

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Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ß-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6-and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4µg/mL). Bactericidal activity (i.e. a mean decrease ≥3 log 10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5-and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log 10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2-and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

The characterization of the functional interactions between the metabotropic glutamate receptors (mGluR) and the dopaminergic (DR) receptors in the corticostriatal projections may provide a possible interpretation of synaptic events in the basal ganglia. It has been suggested that presynaptic D2-type receptor located on glutamatergic corticostriatal neurons regulates the release of glutamate. In a first approach we have studied the cellular distribution of the D4R and the mGluRs in cerebral cortex and striatum employing immunocytochemistry. D4R positive neurons were particularly numerous in medial prefrontal cortex mainly occupying layers II and III. An even distribution was found on small round-shaped neurons in the striatum. Group I mGluR1alpha-like immunoreactivity (mGluR1alpha-LI) was found in medial and deep layers of the cerebral cortex while group III mGluR4a labeled more superficial layers; group II mGluR2/3 signal was intense on fine fibers with a punctate appearance. In the striatum, mGluR1alpha and mGluR2/3 stained mainly fibers while mGluR4a labeled round shaped cell bodies. After lateral ventricular injection of colchicine, an axonal transport and firing activity blocker, D4R labeling significantly increased in cerebral cortex and decreased in the striatum. mGluR1alpha and mGluR4a signal decreased in cerebral cortex and only mGluR4a signal decreased in the striatum. These results support previous reports indicating a presynaptic localization of D4R in the striatum. In contrast, striatal mGluR1alpha appears to be a postsynaptic receptor probably synthesized in situ. Our results do not support the hypothesis of a colocalization of D4 receptor and one or more of the metabotropic glutamatergic receptors studied here.

Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/beta-lactamase inhibitor combination currently available in 29 countries which may be a suitable option for treating intra-abdominal infections. the aim of this study was to identify the optimal dose and ratio between components of this formulation through an ex-vivo human pharmacodynamic model against Escherichia coli. Four volunteers were randomized to receive alternatively a single dose of AMX-SUL infused either over 30 min or 3h in the following ratios (g/g): 1/0.5; 1/1, 2/0.5 and 0/2. time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h post-dosing sera against E. coli ATCC 25922 (AMX MIC, 2 microg/ml; AMX-SUL MIC, 2 microg/ml) and E. coli ATCC 35218 (AMX MIC, 1024 microg/ml; AMX-SUL MIC, 4-8 microg/ml). AMX-SUL 1g/0.5 g infused over 30 min was only active at 0.5 h after dose, being inferior to both AMX-SUL 1g/1g and AMX-SUL 2g/0.5 g against E. coli ATCC 25922, for which the 2h post-dose serum proved active. When tested against E. coli ATCC 35218, AMX-SUL 1g/0.5 g and AMX-SUL 2g/0.5 g were active only at 0.5 h post-dose, whereas AMX-SUL 1g/1g showed bactericidal activity 0.5h post-dose and was able to inhibit bacterial growth 2 h post-dose. When infused over 3h, the antimicrobial activity of AMX-SUL was better than the 30-min infusion. Moreover, AMX-SUL 1g/1g was able to inhibit, and kill to some extent, the E. coli ATCC 25922 strain at 4h post-dose (i.e. 67% and 50% of a 6- and 8-h dosing interval, respectively). The present study suggests that 1g/1g is the best formulation for AMX-SUL against E. coli. The infusion over 3h optimizes its pharmacodynamic profile, as well as that of the 1g/0.5g combination. These findings encourage the performance of clinical trials to assess the efficacy of this combination, given as an extended infusion, in the treatment of community-acquired intra-abdominal infections.