Use of a cerebral protection device to facilitate pulmonary vein isolation in a patient with left atrial mass arising from the interatrial septum.

Sentinel cerebral embolic protection devices (CPDs) may limit periprocedural cerebrovascular events by preventing micro and macro-embolization to the brain, and has been used in many cardiology and radiology procedures. We hereby report the use of a Sentinel CPD to facilitate safe and effective atrial fibrillation ablation in a patient with a left atrial mass arising from the interatrial septum.

Prevalence, incidence and progression of peripheral arterial disease in Asian Indian type 2 diabetic patients.

OBJECTIVE: To assess the prevalence, incidence, etiology and factors related to progression of peripheral arterial disease [PAD] in Asian Indian type 2 diabetic patients. METHODS: Patients with type 2 diabetes (T2DM), with multiple Doppler studies done between 2001 and 2011 at a tertiary diabetes center in south India, were included. Baseline clinical and biochemical characteristics and ankle brachial index [ABI] measurements were abstracted from the electronic medical records. RESULTS: 2512 T2DM patients were followed for an average of 7years. 7.6% of the study population had PAD in 2001 [women, 11.8%; men, 5.1%] with an adjusted odds ratio (OR) of 3.09 [confidence interval (CI): 1.9-4.9] for women. Prevalent PAD was associated with increased mortality [hazards ratio (HR) 3.3, CI: 1.4-7.7]. 280 new patients of PAD were identified - crude incidence, 17/1000 patient years with higher rates in females [HR 1.94, CI: 1.4-2.7]. Age and duration of diabetes were the other predictors of incident PAD. Progression of PAD was seen in 16.5% of patients, with age (p=0.002) and HbA1c (p=0.022) being the predictors. CONCLUSIONS: Women had a higher prevalence of PAD. Older age, female gender and duration of diabetes were related to an increased incidence of PAD. An elevated HbA1c being associated with progression of PAD stresses the need for strict control of diabetes.

Is fecal contamination of drinking water after collection associated with household water handling and hygiene practices? A study of urban slum households in Hyderabad, India.

Water-borne illness, primarily caused by fecal contamination of drinking water, is a major health burden in the state of Andhra Pradesh, India. Currently drinking water is treated at the reservoir level and supplied on alternate days, necessitating storage in households for up to 48 hrs. We hypothesized that fecal contamination occurs principally during storage due to poor water handling. In this study we tested for coliform bacteria in water samples collected at distribution points as household storage containers were filled, and then tested containers in the same households 24-36 hours after collection. We also conducted an observational survey to make an assessment of water handling and hygiene. Ninety-two percent (47/51) of samples tested at supply points were adequately chlorinated and bacterial contamination was found in two samples with no residual chlorine. Samples collected from household storage containers showed an increase in contamination in 18/50 houses (36%). Households with contaminated stored samples did not show significant differences in demographics, water handling, hygiene practices, or sanitation. Nevertheless, the dramatic increase in contamination after collection indicates that until an uninterrupted water supply is possible, the point at which the biggest health impact can be made is at the household level.

Acid-sensing ion channel 3 (ASIC3) cell surface expression is modulated by PSD-95 within lipid rafts.

Acid-sensing ion channel 3 (ASIC3) is a H(+)-gated cation channel primarily found in sensory neurons, where it may function as a pH sensor in response to metabolic disturbances or painful conditions. We previously found that ASIC3 interacts with the postsynaptic density protein PSD-95 through its COOH terminus, which leads to a decrease in ASIC3 cell surface expression and H(+)-gated current. PSD-95 has been implicated in recruiting proteins to lipid rafts, which are membrane microdomains rich in cholesterol and sphingolipids that organize receptor/signaling complexes. We found ASIC3 and PSD-95 coimmunoprecipitated within detergent-resistant membrane fractions. When cells were exposed to methyl-beta-cyclodextrin to deplete membrane cholesterol and disrupt lipid rafts, PSD-95 localization to lipid raft fractions was abolished and no longer inhibited ASIC3 current. Likewise, mutation of two cysteine residues in PSD-95 that undergo palmitoylation (a lipid modification that targets PSD-95 to lipid rafts) prevented its inhibition of ASIC3 current and cell surface expression. In addition, we found that cell surface ASIC3 is enriched in the lipid raft fraction. These data suggest that PSD-95 and ASIC3 interact within lipid rafts and that this raft interaction is required for PSD-95 to modulate ASIC3.

ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation.

Peripheral initiators of muscle pain are virtually unknown, but likely key to development of chronic pain after muscle insult. The current study tested the hypothesis that ASIC3 in muscle is necessary for development of cutaneous mechanical, but not heat, hyperalgesia induced by muscle inflammation. Using mechanical and heat stimuli, we assessed behavioral responses in ASIC3-/- and ASIC3+/+ mice after induction of carrageenan muscle inflammation. ASIC3-/- mice did not develop cutaneous mechanical hyperalgesia after muscle inflammation when compared to ASIC3+/+ mice; heat hyperalgesia developed similarly between groups. We then tested if the phenotype could be rescued in ASIC3-/- mice by using a recombinant herpes virus vector to express ASIC3 in skin (where testing occurred) or muscle (where inflammation occurred). Infection of mouse DRG neurons with ASIC3-encoding virus resulted in functional expression of ASICs. Injection of ASIC3-encoding virus into muscle or skin of ASIC3-/- mice resulted in ASIC3 mRNA in DRG and protein expression in DRG and the peripheral injection site. Injection of ASIC3-encoding virus into muscle, but not skin, resulted in development of mechanical hyperalgesia similar to that observed in ASIC3+/+ mice. Thus, ASIC3 in primary afferent fibers innervating muscle is critical to development of hyperalgesia that results from muscle insult.

Stomatin modulates gating of acid-sensing ion channels.

Acid-sensing ion channels (ASICs) are H(+)-gated members of the degenerin/epithelial Na(+) channel (DEG/ENaC) family in vertebrate neurons. Several ASICs are expressed in sensory neurons, where they play a role in responses to nociceptive, taste, and mechanical stimuli; others are expressed in central neurons, where they participate in synaptic plasticity and some forms of learning. Stomatin is an integral membrane protein found in lipid/protein-rich microdomains, and it is believed to regulate the function of ion channels and transporters. In Caenorhabditis elegans, stomatin homologs interact with DEG/ENaC channels, which together are necessary for normal mechanosensation in the worm. Therefore, we asked whether stomatin interacts with and modulates the function of ASICs. We found that stomatin co-immunoprecipitated and co-localized with ASIC proteins in heterologous cells. Moreover, stomatin altered the function of ASIC channels. Stomatin potently reduced acid-evoked currents generated by ASIC3 without changing steady state protein levels or the amount of ASIC3 expressed at the cell surface. In contrast, stomatin accelerated the desensitization rate of ASIC2 and heteromeric ASICs, whereas current amplitude was unaffected. These data suggest that stomatin binds to and alters the gating of ASICs. Our findings indicate that modulation of DEG/ENaC channels by stomatin-like proteins is evolutionarily conserved and may have important implications for mammalian nociception and mechanosensation.