Expression of the endoplasmic reticulum stress response marker, BiP, in the central nervous system of HIV-positive individuals

The prevalence of HIV-associated neurocognitive impairment (NCI), which includes HIV-associated dementia (HAD) and minor cognitive and motor disorder (MCMD), has been increasing. HIV-infected and/or activated macrophages/microglia in the brain initiate the neurodegeneration seen in HIV-associated NCI via soluble neurotoxic mediators, including reactive oxygen species, viral proteins and excitotoxins. Neurotoxic factors released by macrophages/microglia injure neurones directly and alter astrocytic homeostatic functions, which can lead to excitotoxicity and oxidative stress-mediated neuronal injury. Often, cells respond to oxidative stress by initiating the endoplasmic reticulum (ER) stress response. Thus, we hypothesize that ER stress response is activated in HIV-infected cortex. We used immunofluorescence and immunoblotting to assess expression patterns of the ER stress proteins, BiP and ATF6, in HIV-positive cortical autopsy tissue. Additionally, we performed immunofluorescence using cell type-specific markers to examine BiP staining in different cell types, including neurones, astrocytes and macrophages/microglia. We observed a significant increase in BiP expression by both immunoblotting and immunofluorescence in HIV-positive cortex compared with control tissue. Additionally, phenotypic analysis of immunofluorescence showed cell type-specific increases in BiP levels in neurones and astrocytes. Further, ATF-6beta, an ER stress response initiator, is up-regulated in the same patient group, as assessed by immunoblotting. These results suggest that ER stress response is activated in HIV-infected cortex. Moreover, data presented here indicate for the first time that numbers of macrophages/microglia increase in brains of MCMD patients, as has been observed in HAD.     

Management of a retained catheter in an arteriovenous malformation. Case report

The long-term effects of retained catheters in patients are not well known; therefore, the clinical presentation may differ. The authors present the case of a 21-year-old man with a pseudoaneurysm of the left common femoral artery, which developed 3 months after a transfemoral microcatheter embolization of a cerebral arteriovenous malformation (AVM) in which the catheter was inadvertently glued into the AVM and was retained at the groin.     

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y₁, P2Y₁₂, CYP2C9, CYP3A4 and CYP3A5 genotypes.     

Depth perception differences between hemispheres, genders, and eye dominance A study on evoked potential

BACKGROUND： Certain neural functions, such as peripheral reflexes, differ between genders, while higher brain functions, such as language, are asymmetrically distributed between the two hemispheres. The question remains as to whether depth perception differs between hemispheric laterality and genders, and whether it is affected by eye dominance. OBJECTIVE： To determine whether depth perception is influenced by factors such as gender, eye dominance, and hemispheric lateralization by recording evoked potential associated with depth perception. DESIGN, TIME AND SETTING： A contrast observation based on neuroelectrophysiology was performed at the Department of Biophysics of Ege University Medical School between June 2006 and April 2007. PARTICIPANTS： A total of 34 subjects, 19 females and 15 males, were included in the study with a mean age of （31.0 ± 6.9） years. All subjects were free of neurological or psychological disorders, or problems such as strabismus or vision correction. METHODS： Random-dot stereograms were used to elicit brain activity. A specially designed signal acquisition system employing two computers was used to record evoked potentials from both hemispheres via two pairs of scalp electrodes placed over the occipitotemporal areas of both hemispheres at symmetrical locations. MAIN OUTCOME MEASURES： Negative potential with a mean latency of （211.21 ±25.55） ms and a mean amplitude of （6.05 ± 1.53） pV was recorded from both occipitotemporal areas in 30 out of 34 participants. This was termed ＂Nd＂ and represented the evoked potential associated with depth perception. RESULTS： There were no significant differences in Nd amplitude or latency between the two hemispheres, the two eyes, or genders （P 〉 0.05）. CONCLUSION： The evoked potential associated with depth perception was not influenced by gender, hemisphere, or eye dominance.     

Mechanism of asynchronous Ca2+ waves underlying agonist-induced contraction in the rat basilar artery

Background and purpose:

Uridine 5''-triphosphate (UTP) is a potent vasoconstrictor of cerebral arteries and induces Ca²⁺ waves in vascular smooth muscle cells (VSMCs). This study aimed to determine the mechanisms underlying UTP-induced Ca²⁺ waves in VSMCs of the rat basilar artery.

Experimental approach:

Isometric force and intracellular Ca²⁺ ([Ca²⁺]_i) were measured in endothelium-denuded rat basilar artery using wire myography and confocal microscopy respectively.

Key results:

Uridine 5''-triphosphate (0.1–1000 µmol·L⁻¹) concentration-dependently induced tonic contraction (pEC₅₀ = 4.34 ± 0.13), associated with sustained repetitive oscillations in [Ca²⁺]_i propagating along the length of the VSMCs as asynchronized Ca²⁺ waves. Inhibition of Ca²⁺ reuptake in sarcoplasmic reticulum (SR) by cyclopiazonic acid abolished the Ca²⁺ waves and resulted in a dramatic drop in tonic contraction. Nifedipine reduced the frequency of Ca²⁺ waves by 40% and tonic contraction by 52%, and the nifedipine-insensitive component was abolished by SKF-96365, an inhibitor of receptor- and store-operated channels, and KB-R7943, an inhibitor of reverse-mode Na⁺/Ca²⁺ exchange. Ongoing Ca²⁺ waves and tonic contraction were also abolished after blockade of inositol-1,4,5-triphosphate-sensitive receptors by 2-aminoethoxydiphenylborate, but not by high concentrations of ryanodine or tetracaine. However, depletion of ryanodine-sensitive SR Ca²⁺ stores prior to UTP stimulation prevented Ca²⁺ waves.

Conclusions and implications:

Uridine 5''-triphosphate-induced Ca²⁺ waves may underlie tonic contraction and appear to be produced by repetitive cycles of regenerative Ca²⁺ release from the SR through inositol-1,4,5-triphosphate-sensitive receptors. Maintenance of Ca²⁺ waves requires SR Ca²⁺ reuptake from Ca²⁺ entry across the plasma membrane via L-type Ca²⁺ channels, receptor- and store-operated channels, and reverse-mode Na⁺/Ca²⁺ exchange.     

Hepatic haemorrhage after thrombolytic administration in a patient with myocardial infarction who had a trauma: are we missing something?

Myocardial infarction (MI) typically presents with chest pain, dyspnoea and pain in the left arm. In some cases, syncope may ensue and the patients can have blunt trauma to the abdomen, chest or head, which may be overlooked by the doctors and the patient, with more concern focusing on infarction alone. Moreover, signs of trauma may not appear until late in the course of hospitalisation. The patient reported on here had abdominal trauma following a syncopic event, resulting from an inferoposterior MI. Administration of thrombolytic treatment led to a hepatic haemorrhage. This life-threatening complication might have been prevented by a bedside ultrasonography performed by an emergency medicine doctor. This effective use of time can be remembered as "time is muscle".     

The first reported case of lichen planus following inactivated influenza vaccination

Lichen planus (LP) is an idiopathic, inflammatory, pruritic dermatosis of unknown origin. An increased prevalence of a wide range of diseases such as viral hepatitis C, hepatitis B, primary sclerosing cholangitis, and primary biliary cirrhosis have been associated with LP. Recently, LP has been reported following administration of different types of hepatis B vaccines but a relationship with an inactivated influenza vaccine (Fluarix, GlaxoSmithKline) has not been reported previously. We present a case of generalized LP manifesting 7 days after the first 0.5-ml dose of influenza vaccine, administered via deltoid injection. LP is possibly a viral antigen-triggered inflammatory skin condition, the pathogenesis of which needs to be further explored.