Oxidative Stress in HIV Infection and Alcohol Use: Role of Redox Signals in Modulation of Lipid Rafts and ATP-Binding Cassette Transporters.

AIMS: Human immunodeficiency virus (HIV) infection induces oxidative stress and alcohol use accelerates disease progression, subsequently causing immune dysfunction. However, HIV and alcohol impact on lipid rafts-mediated immune dysfunction remains unknown. In this study, we investigate the modulation by which oxidative stress induces reactive oxygen species (ROS) affecting redox expression, lipid rafts caveiloin-1, ATP-binding cassette (ABC) transporters, and transcriptional sterol regulatory element-binding protein (SREBP) gene and protein modification and how these mechanisms are associated with arachidonic acid (AA) metabolites in HIV positive alcohol users, and how they escalate immune dysfunction. RESULTS: In both alcohol using HIV-positive human subjects and in vitro studies of alcohol with HIV-1 gp120 protein in peripheral blood mononuclear cells, increased ROS production significantly affected redox expression in glutathione synthetase (GSS), super oxide dismutase (SOD), and glutathione peroxidase (GPx), and subsequently impacted lipid rafts Cav-1, ABC transporters ABCA1, ABCG1, ABCB1, and ABCG4, and SREBP transcription. The increased level of rate-limiting enzyme 3-hydroxy-3-methylglutaryl HMG-CoA reductase (HMGCR), subsequently, inhibited 7-dehydrocholesterol reductase (DHCR-7). Moreover, the expression of cyclooxygenase-2 (COX-2) and lipoxygenase-5 (5-LOX) mRNA and protein modification tentatively increased the levels of prostaglandin E2 synthases (PGE2) in plasma when compared with either HIV or alcohol alone. INNOVATION: This article suggests for the first time that the redox inhibition affects lipid rafts, ABC-transporter, and SREBP transcription and modulates AA metabolites, serving as an important intermediate signaling network during immune cell dysfunction in HIV-positive alcohol users. CONCLUSION: These findings indicate that HIV infection induces oxidative stress and redox inhibition, affecting lipid rafts and ABC transports, subsequently upregulating AA metabolites and leading to immune toxicity, and further exacerbation with alcohol use. Antioxid. Redox Signal. 28, 324-337.

The effect of alcohol use on IL-6 responses across different racial/ethnic groups.

AIMS: Chronic inflammation has become increasingly recognized as a health threat for people living with HIV, given its associations with multiple diseases. Accordingly, the scientific community has prioritized the need to identify mechanisms triggering inflammation. PARTICIPANTS METHODS: A clinic-based case-control study was designed to elucidate the plausible effects of alcohol use on IL-6. Peripheral blood mononuclear cells for measuring IL-6 culture supernatant and plasma for HIV assessments were collected from 59 hazardous alcohol users and 66 nonhazardous alcohol users, who were matched according to their age, gender and US CDC HIV severity status. RESULTS: Stimulated peripheral blood mononuclear cells produced significantly higher amounts of IL-6 in hazardous alcohol users compared with nonhazardous alcohol users. However, racial status and receiving HAART significantly moderated this effect. Notably, in both HAART and non-HAART scenarios, IL-6 levels were associated with CD4 counts and viral burden. A distinctive IL-6 production pattern across racial/ethnic groups was also evident and showed that, when prescribed HAART, Hispanic hazardous alcohol users have a particularly high risk of morbidity compared with their Caucasian and African-American counterparts. After adjusting for confounders (e.g., sociodemographics and HIV disease status), regression analyses confirmed that chronic inflammation, as indicated by IL-6 levels (log), is associated with alcohol use, race/ethnicity and thrombocytopenia, and tended to be related to concurrent smoking. CONCLUSION: Our data confirm that, despite HAART, people living with HIV still have a persistent inflammatory response that, in our study, was associated with chronic hazardous alcohol use. The data also highlight racial/ethnic disparities in IL-6 that justify further investigations.

The importance of HIV status and gender when designing prevention strategies for anal cancer.

Our objective is to review and summarize relevant aspects of the literature regarding human papillomavirus (HPV), the most common sexually transmitted infection in the United States, and to compare how the trajectory of HPV may differ in persons who are and who are not co-infected with HIV. This comparison is particularly important because the literature on HPV has been largely based on individuals who are not co-infected with HIV. Also, HPV findings may differ in HIV-uninfected individuals versus HIV-infected individuals. In addition, many reviews ignore gender differences, although in HIV-uninfected individuals, anal cancers are up to 4 times more prevalent in women than men. Clinical decision making may be problematic if such critical factors as HIV status and gender are neglected. Therefore, we will review existing information on how HIV status and gender may affect the manifestation of HPV, particularly focusing on epidemiology, screening, and treatment issues.

Cholesterol as a Mediator of Alcohol-Induced Risks for Respiratory Disease Hospitalizations among People Living With HIV.

We analyzed the role of cholesterol as a potential mediator of alcohol-increased risk of respiratory infections that required hospitalization in People Living with HIV (PLWH). Using a longitudinal clinic-based design, 346 PLWH were consecutively admitted and followed at Jackson Memorial Medical Center(enrolled in the study). Following national guidelines, PLWH were stratified according to cholesterol levels: <150 mg/dl (Hypocholesterolemia= HypoCHL), 151-200, and >200 mg/dl Hypercholesterolemia =HyperCHL), and compared on the basis of clinical outcomes, lymphocyte phenotypes and behavioral risks. Analyses indicated that compared to HyperCHL participants, HypoCHL subjects were more likely to be hospitalized, particularly for lower respiratory tract infections (LRTI). Excessive admissions were associated with more deviant lymphocyte profiles, particularly limited NK cells. In logistic regression analyses, smoking (OR=1.5), HypoCHL (OR=7.7), and alcohol (OR=1.2) were predictors of LRTI. These findings warrant further investigation of the potential use of HypoCHL as a risk marker, and the cost-effectiveness of switching prevention gears towards HypoCHL, alcohol and tobacco in PLWH.

Evaluation of intraocular pressure in the immediate postoperative period after phacoemulsification.

PURPOSE: To determine the incidence of hypotony and intraocular pressure (IOP) elevation in the immediate and early postoperative period after temporal posterior limbal phacoemulsification and intraocular lens (IOL) implantation. SETTING: Ambulatory surgical center. METHODS: This prospective analysis comprised 310 eyes that had temporal posterior limbal phacoemulsification with IOL implantation. Surgical parameters included keratome incision of 2.85 mm, incision length of 2.5 mm, peribulbar anesthesia, case-completion IOP of 20 mm Hg, and postoperative lid taping. The IOP measurements were collected preoperatively and 30 minutes and 1 day after surgery. RESULTS: Nineteen eyes (6.1%) had an IOP lower than 5 mm Hg 30 minutes postoperatively in the absence of incision leakage at the paracentesis or keratome sites. Eighteen of the 19 eyes with postoperative hypotony received hydroxypropyl methylcellulose 2% (OcuCoat) and 1 received hypromellose 2% (Cellugel). None of the 23 eyes with an acrylic IOL implanted via a cylindrical lens inserter had an IOP lower than 5 mm Hg postoperatively. Suturing did not significantly affect the incidence of hypotony, and there were no postoperative complications related to hypotony. The mean IOP at 30 minutes was lower than at 1 day in the normal, glaucoma, and glaucoma-suspect groups. Twenty-one normal eyes (8.1%), 5 glaucoma eyes (15.6%), and 1 glaucoma-suspect eye (5%) had an IOP greater than 30 mm Hg 1 day postoperatively. CONCLUSIONS: Postoperative hypotony (IOP <5 mm Hg) occurred in 19 (6.1%) of 310 eyes. At 1 day, IOP higher than 30 mm Hg was more frequent in glaucoma eyes than in normal eyes. Although there were no direct problems related to hypotony at 30 minutes or to elevated IOP (>30 mm Hg) at 1 day, surgeons should be aware of and check for IOP variability (low and high) that can occur in normal, glaucoma, and glaucoma-suspect eyes within the first 24 hours after surgery.

An unusual case of rhabdomyosarcoma presenting as orbital apex syndrome.

PRECIS: A 12-year-old female presented with symptoms and signs of orbital apex syndrome (OAS), secondary to stage IV alveolar rhabdomyosarcoma (RMS) originating in the sphenoid and ethmoid sinuses. OBJECTIVE: To present a case of alveolar rhabdomyosarcoma, unusual in its presentation as orbital apex syndrome and also its origin from the sphenoid and ethmoid sinuses. DESIGN: : Observational case report. METHODS: Ophthalmologic findings, neuroimaging, medical and surgical intervention, histopathologic analysis, and clinical course are described. RESULTS: A 12-year-old female presented with progressive visual loss in her left eye, difficulty with eye movements, and mild headache. Her examination was consistent with orbital apex syndrome. Imaging with contrast revealed a mass originating in the left sphenoid and ethmoid sinuses invading the left optic canal. Emergent biopsy was interpreted as alveolar rhabdomyosarcoma; subsequent metastatic work-up revealed bone marrow metastases. The patient was diagnosed with stage IV alveolar rhabdomyosarcoma and immediately started on combination orbital radiation therapy (RT) and systemic chemotherapy. She experienced gradual improvement of ocular motility, though her optic neuropathy persisted. CONCLUSION: Alveolar rhabdomyosarcoma of paranasal origin, specifically from the sphenoid and ethmoid sinuses, should be included in the differential diagnosis for orbital apex syndrome in children.