Epidemiologic and clinical characteristics of infective endocarditis: a single-center retrospective study in the Bronx, New York.

OBJECTIVE: There is paucity of data on the epidemiological, microbiological, and clinical characteristics of patients admitted with infective endocarditis (IE) in the Bronx, New York. PATIENT AND METHODS: We conducted a retrospective study at Jacobi Medical Center, a tertiary care hospital in the Bronx. All adult patients who were hospitalized with a primary diagnosis of new-onset IE between January 1st, 2010 and September 30th, 2020 were included. The primary outcome was in-hospital mortality. A logistic regression model was used to identify baseline variables associated with in-hospital mortality. RESULTS: 182 patients were included in this analysis (female sex: 38.5%, median age: 54 years). 46 patients (25.3%) reported intravenous drug use. 153 patients (84.1%) had positive blood cultures. Staphylococcus aureus (S. aureus) was the most common isolated pathogen (45.1% of monomicrobial IE). Nearly half of the cases secondary to S. aureus were methicillin resistant Staphylococcus aureus (MRSA) (34/69). 164 patients (90.1%) were diagnosed with native valve IE. The mitral valve was involved in 32.4% of patients followed by the aortic valve (19.8%). The in-hospital mortality was 18.1%. The mortality was higher in the cohort 2010-2015 compared to the cohort 2016-2020 (22.1% vs 14.6%). Increasing age, MRSA IE, and active malignancy were the only variables found to have significant association with in-hospital death. CONCLUSION: S. aureus was the most common causative agent and MRSA accounted for about half of the S. aureus IE cases. The incidence of IE in patients with intravenous drug use increased over time, while the median age decreased. The in-hospital death rate was higher in 2010-2015 compared to 2016-2020.

Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study.

Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly increased the release of glutamate, which may cause neurotoxicity. Simultaneously, cocaine challenge after withdrawal also significantly increased the release of taurine, which counteracts glutamate-mediated excitotoxicity and possibly cell death. Thus, the mammalian brain has an endogenous self-protective mechanism against cocaine-mediated neurotoxicity and potentially addiction.

Cortical plasticity in Alzheimer's disease in humans and rodents.

BACKGROUND: The aim of this study was to determine whether neocortical long-term potentiation (LTP) is deficient in patients with Alzheimer's disease (AD) and in amyloid precursor protein (APP)/presenilin-1 (PS1) mice, an AD animal model. We then ascertained whether this deficit might be paralleled by functional abnormalities of N-methyl-D-aspartate (NMDAR) glutamate receptors. METHODS: We studied neocortical LTP-like plasticity in 10 patients with mild-to-moderate AD and 10 age-matched normal controls using paired associative stimulation (PAS). We assessed neocortical (medial prefrontal cortex and primary motor cortex) and hippocampal LTP in brain slices of symptomatic APP/PS1 mice. NMDAR composition and signaling as well as synaptic calcium influx were determined in motor, prefrontal and hippocampal cortices of APP/PS1 mice. RESULTS: Both AD patients and transgenic animals showed a deficit in NMDAR-dependent forms of neocortical plasticity. Biochemical analysis showed impaired NMDAR function in symptomatic APP/PS1 mice. CONCLUSIONS: Neocortical plasticity is impaired in both patients with AD and APP/PS1 mice. The results of our biochemical studies point to impaired NMDAR function as the most likely cause for the neocortical plasticity deficit in AD.

Altered excitability and distribution of NMDA receptor subunit proteins in cortical layers of rat pups following multiple perinatal seizures.

During a critical period of postnatal development the epileptogenic focus is thought to be of cortical origin. We used immunohistochemistry and Western blotting to elucidate potential mechanisms underlying an increased state of susceptibility to seizures in immature animals. Distribution patterns of N-methyl-D-aspartic acid (NMDA) (NR1 and NR2A/B) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) (GluR1 and GluR2) subunits were analyzed in retrosplenial, parietal and temporal cortices during the first two postnatal weeks following three episodes of status-epilepticus. Rat pups were injected three times with kainic acid (3x KA) on P6, P9, and P13 and subsequently sacrificed 48 h after the third seizure. Cortical electroencephalography (EEG) showed increased number of spikes and bursts of longer duration after 3x KA. Immunodensity measurements after 3x KA revealed a robust increase in NR2A/B labeling specific to cortical layer V throughout the retrosplenial, parietal, and temporal cortices, with no changes noted in piriform cortex. NR1 layer V immunoreactivity was also simultaneously increased in serial sections but to a lesser degree; heightened immunodensities were specific to retrosplenial and temporal cortices. The NR1:NR2 ratio was decreased in cortical layer V of the temporal and retrosplenial cortices but not in parietal cortex despite elevated immunoreactivity. Steady levels of GluR1 and GluR2 subunits were noted in all cortical areas studied in the same animals. Thus, recurrent perinatal seizures led to selective and layer-specific increases in NMDA receptor proteins. These changes may be responsible for lowering the seizure threshold in deeper cortical areas and eventually contribute to the cortical epileptogenic focus.

Distinct regulation of metabotropic glutamate receptor (mGluR1 alpha) in the developing limbic system following multiple early-life seizures.

The effects of repeated neonatal seizures on metabotropic glutamate receptors (mGluRs) during critical periods of brain development are unknown. Therefore, we characterized the expression of Group I (mGluR1 and mGluR5) and Group II (mGluR2/3) metabotropic glutamate receptor proteins in the developing limbic system in response to a varied neonatal seizure history. Status epilepticus was induced with kainic acid (KA) either once (1x KA) on postnatal (P) day (P13), twice (2x KA) on P6 and P9 or P13, or three times (3x KA) on P6, P9, and P13. In control hippocampus, mGluR1alpha protein expression differed at all stages of development examined, whereas mGluR2/3 and mGluR5 protein expression patterns were mature by P15. After KA-induced status epilepticus, there was a significant elevation in mGluR1alpha protein expression within a select group of inhibitory interneurons of the CA1 stratum oriens-alveus that was enhanced with increasing number of neonatal seizures. mGluR2/3 and mGluR5 subtypes were unchanged. Increases were also observed within neurons of the amygdala and piriform cortex. Selective increases of mGluR1alpha subtypes within limbic structures may contribute to the resistance and tolerance of the immature hippocampus from damage. This may occur by excessive stimulation of excitatory synapses to collectively enhance the inhibitory drive of the immature brain by increasing GABA release. Data suggest that the mGluR1alpha subtype plays an important role in regulating hippocampal network activity after early-life seizures.

Clozapine protection against gestational cocaine-induced neurochemical abnormalities.

Clozapine was found to be effective in attenuating cocaine-induced neurochemical effects. We investigate whether clozapine influences in utero cocaine exposure-induced changes in striatal dopamine levels and cortical N-methyl-D-aspartate (NMDA) receptor density in mouse and rat brains. Pregnant mice or rats were injected with cocaine (5 or 10 mg/kg intraperitoneally) or saline every 24 h throughout gestation and continued for 6 weeks following the delivery. Striatal dopamine levels measured by high-pressure liquid chromatography were found to decrease 24 to 33% in gestational cocaine exposed between the ages of 3 to 15 days, but not in 42-day-old pups. The cortical NMDA receptor densities assessed either in the presence of 100 microM glutamate or 30 microM glycine were significantly increased in 15-day-old gestational cocaine-exposed rats. Simultaneous daily administration of 3 mg/kg clozapine with 5 mg/kg cocaine to pregnant mice protected against the decrease in striatal dopamine levels or an increase in the concentration of NMDA receptor measured in the presence of 100 microM glutamate in 15-day-old pups. Clozapine did not affect striatal dopamine levels by itself or when coadministered with cocaine in 42-day-old pups. The results show gestational cocaine may induce neurochemical abnormalities in brain exhibited as an increased glutamate NMDA receptor density together with a decreased striatal dopamine level. These effects of gestational cocaine exposure may be prevented by simultaneous administration of clozapine. Thus clozapine, which is a partial agonist at the NMDA receptor, may be of value in protecting against gestational cocaine-induced adverse effects in the brain.