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Early Targeting of L-Selectin on Leukocytes Promotes Recovery after Spinal Cord Injury, Implicating Novel Mechanisms of Pathogenesis

McCreedy, D A; Lee, S; Sontag, C J; Weinstein, P; Olivas, A D; Martinez, A F; Fandel, T M; Trivedi, A; Lowell, C A; Rosen, S D; Noble-Haeusslein, L J
L-selectin, a lectin-like receptor on all leukocyte classes, functions in adhesive and signaling roles in the recruitment of myeloid cells from the blood to sites of inflammation. Here, we consider L-selectin as a determinant of neurological recovery in a murine model of spinal cord injury (SCI). Spinal cord-injured, L-selectin knock-out (KO) mice (male) showed improved long-term recovery with greater white matter sparing relative to wild-type (WT) mice and reduced oxidative stress in the injured cord at 72 h post-SCI. There was a partial and transient reduction in accumulation of neutrophils in the injured spinal cords of KOs at 24 h post-injury. To complement these findings with KO mice, we sought a pharmacologic means for lowering L-selectin levels. We found that diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), induced the shedding of L-selectin from the cell surface of myeloid subsets, specifically neutrophils and non-classical monocytes, in the blood and the injured spinal cord. Diclofenac administration to injured WT mice enhanced neurological recovery to a level comparable to that of KOs but did not improve recovery in KOs. While diclofenac treatment had no effect on myeloid cell accumulation, there was a reduction in oxidative stress at 72 h post-SCI. These findings implicate L-selectin in secondary pathogenesis beyond a role in leukocyte recruitment and raise the possibility of repurposing diclofenac for the treatment of SCI.
PMCID:6140118
PMID: 30225356
ISSN: 2373-2822
CID: 4276622

Mutans streptococci prevalence in Puerto Rican babies with cariogenic feeding behaviors

Lopez, L; Berkowitz, R J; Moss, M E; Weinstein, P
PURPOSE: Previous studies have demonstrated that babies are at higher risk for mutans streptococci (ms) colonization if their mothers have dense salivary ms reservoirs relative to babies who have mothers with negligible salivary reservoirs. This communication provides data that identifies another potential risk factor (use of a nursing bottle at bedtime and/or naptime that contains a substrate other than water) for baby infection by ms. METHODS: The study population consisted of 60 babies (28 males/32 females; mean age 15 mos; age range 12-18 mos) who were all healthy, caries free, and slept with a nursing bottle that contained a substrate other than water (NB+). Pooled maxillary incisor plaque and saliva samples were obtained and immediately placed in Reduced Transparent Fluid (RTF); they were serially diluted and plated onto Mitis Salivarius Agar plus Bacitracin (MSB) and blood agar plates within 4 hours of collection; the plates were incubated in an anaerobic environment for 48 h at 37 C and then placed for 24 h under aerobiosis prior to examination; representative ms colonies were isolated and subjected to mannitol and sorbitol fermentation tests for taxonomic verification. Plates with colony counts between 20 and 300 were utilized to determine the % of ms in each sample. RESULTS: Fifty one of the 60(85%) babies harbored ms in at least 1 of the 2 samples. The 95% confidence interval for the proportion of subjects with detectable levels of ms was 73%-93%. Fisher's exact test showed that babies 16-18 mos age were more likely to have detectable levels of ms than babies 12-15 mos age (p = 0.01). Levels of ms in plaque and saliva were as follows: < 0.1% (plaque 27/51, mean age 15 mos, sd 1.77; saliva 28/51, mean age 15 mos, sd 1.76); 0.1%-1.0% (plaque 4/51, mean age 14 mos, sd 1.5; saliva 6/51, mean age 15 mos, sd 1.46); > 1.0% (plaque 14/51, mean age 16 mos, sd 2.1; saliva 11/51, mean age 16 mos, sd 1.91). The density of infection did not vary by age for plaque (P = 0.32) or saliva (P = 0.64). CONCLUSION: These findings support the concept that NB+ is a strong indicator for ms infection in Puerto Rican babies; that prevalence of infection increases with age; and that density of infection does not vary with age in this population.
PMID: 10969436
ISSN: 0164-1263
CID: 163712

Bilateral keratitis as a manifestation of Lyme disease [Case Report]

Baum, J; Barza, M; Weinstein, P; Groden, J; Aswad, M
An 11-year-old girl developed bilateral keratitis, which we believe was a manifestation of Lyme disease. She had had several attacks of Lyme arthritis and was twice treated with parenteral penicillin. The keratitis developed five years after the initial episode of Lyme arthritis at a time when there were no other manifestations of Lyme disease. It cleared completely in both eyes after topical corticosteroid therapy.
PMID: 3337196
ISSN: 0002-9394
CID: 2134002