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Glutamate-induced excitotoxicity has been implicated as an important mechanism underlying a variety of brain injuries and neurodegenerative diseases. Previously we have shown that taurine has protective effects against glutamate-induced neuronal injury in cultured neurons. Here we propose that the primary underlying mechanism of the neuroprotective function of taurine is due to its action in preventing or reducing glutamate-induced elevation of intracellular free calcium, [Ca(2+)](i). This hypothesis is supported by the following findings. First, taurine transport inhibitors, e.g., guanidinoethyl sulfonate and beta-alanine, have no effect on taurine's neuroprotective function, suggesting that taurine protects against glutamate-induced neuronal damage through its action on the extracellular membranes. Second, glutamate-induced elevation of [Ca(2+)](i) is reduced to the basal level upon addition of taurine. Third, pretreatment of cultured neurons with taurine prevents or greatly suppresses the elevation of [Ca(2+)](i) induced by glutamate. Furthermore, taurine was found to inhibit the influx but not the efflux of (45)Ca(2+) in cultured neurons. Taurine has little effect on the binding of [(3)H]glutamate to the agonist binding site and of [(3)H]MDL 105,519 to the glycine binding site of the N-methyl-D-aspartic acid receptors, suggesting that taurine inhibits (45)Ca(2+) influx through other mechanisms, including its inhibitory effect on the reverse mode of the Na(+)/Ca(2+) exchangers (Wu et al. [2000] In: Taurine 4: taurine and excitable tissues. New York: Kluwer Academic/Plenum Publishers. p 35-44) rather than serving as an antagonist to the N-methyl-D-aspartic acid receptors.

Background HIV-infected individuals have a higher incidence of head and neck cancer. Methods Case series of 94 HIV-infected head and neck cancer patients (HIV-HNC) at six tertiary care referral centers in the US between 1991–2011. Clinical and risk factor data were abstracted from the medical record. Risk factors for survival were analyzed using Cox proportional hazard models. Human papillomavirus (HPV) and p16 testing was performed in 46 tumors. Findings were compared with SEER HNC (US-HNC) data. Results This study represents the largest HIV-HNC series reported to date. HIV-HNC cases were more likely than US-HNC to be male (91% vs. 68%), younger (median 50 vs. 62 years), non-White (49% vs.18%), and current smokers (61% vs. 18%). Median HIV-HNC survival was not appreciably lower than US-HNC survival (63 vs. 61 months). At diagnosis, most cases were currently on HAART (77%), but had detectable HIV viremia (99%) and median CD4 was 300 cells/μL (IQR=167–500). HPV was detected in 30% of HIV-HNC and 64% of HIV-oropharyngeal cases. Median survival was significantly lower among those with CD4 counts ≤200 than >200 cells/μL at diagnosis (16.1 vs. 72.8 months, p<0.001). In multivariate analysis, poorer survival was associated with CD4 <100 cells/μL (aHR=3.09, 95%CI=1.15–8.30), larynx/hypopharynx site (aHR=3.54, 95%CI=1.34–9.35), and current tobacco use (aHR=2.54, 95%CI=0.96–6.76). Conclusion Risk factors for the development of HNC in patients with HIV infection are similar to the general population, including both HPV-related and tobacco/alcohol-related HNC.

BackgroundRapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population.MethodsThe Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit.ResultsThere were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25–45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62–96) to 57 (41–70) days (P < .0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P < .0001), each remaining significant in adjusted models.ConclusionsThis is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.