Visual Evidence of Ischemic Preconditioning During PCI Using 80 Lead ECG Body Surface Mapping

Ischemic preconditioning (IPC) is a well-documented phenomenon. Short episodes of sublethal ischemia provide cardioprotective effects for subsequent longer duration ischemic events. Although the exact mechanism of IPC is not yet known, the chemical basis of IPC seems to involve preservation of ATP or collateral vascularization recruitment. In this case report, we present visual evidence of ischemic preconditioning using Heartscape Technologies 80 Lead ECG device. The 80 Lead ECG is described as a body surface mapping modality, converting its inputted 80 lead ECG data into a 3-Dimensional color coded map. The 80 lead ECG device can detect instantaneous ischemic changes. Different studies have been performed to show different clinical and biochemical aspects of IPC. However data regarding direct visual evidence of this phenomenon is lacking. The secondary objective of this study is to show the ability of 80 lead ECG to identify ST-segment elevation and depression during ischemic events. The utility of 80 Lead ECG body surface mapping is enormous when evaluating ischemic events

Sex differences in inflammatory cytokine production in hepatic ischemia-reperfusion

BACKGROUND: The inflammatory response to hepatic ischemia-reperfusion (I/R) is associated with an increase in cytokine production. Studies have documented that sex hormones modulate both the innate and adaptive immune responses, and that females are more robust than males. The aim of this study was to determine whether a sex difference in cytokine response to hepatic I/R exists under normal pathophysiologic condition without hormone intervention. METHODS: Adult C57BL/6 mice underwent 90 min of hepatic ischemia followed by various reperfusion periods (0, 1.5, 3, 6 hr). Plasma cytokine TNF-α, IL-6, MIP-2, and KC were measured. Liver injury was assessed by plasma alanine transaminase (ALT) levels and liver histopathology. RESULTS: A reperfusion time-dependent increase in hepatocellular injury was observed in both males and females, as indicated by increasing levels of plasma ALT and liver histopathology. The plasma cytokines were significantly increased in both female and male I/R groups compared to their respective sham counterparts. However, there was a significant difference in cytokine kinetics between the female and male I/R groups. Female mice initially had a higher level of IL-6, KC, and MIP-2 in response to I/R, which began to decline after 3 hr of reperfusion and were significantly lower than the male I/R counterparts by 6 hr of reperfusion. In contrast, the hepatocellular injury and TNF production were only moderately lower in female IR than male IR. CONCLUSION: The study underscores role of the gender in differential inflammatory cytokine expression in response to hepatic I/R, which may reflect the host response outcome

ATP-dependent potassium channels are implicated in simvastatin pretreatment-induced inhibition of apoptotic cell death after renal ischemia/reperfusion injury

Background: Simvastatin is a widely used medication in cardiac care. Here we evaluate the role of ATP sensitive potassium (KATP) channels in simvastatin induced renal protection after renal ischemia/reperfusion (I/R) injury. Methods: A total of 81 male Wistar rats, were treated with simvastatin (10 and 20mg/kg/day; gavage, one week). Some groups received glibenclamide (KATP channel inhibitor; 5mg/kg) before ischemia (45min) and reperfusion (24h). Finally the kidneys were processed for histological analysis and measurement of biochemical parameters including tissue malondialdehyde (MDA), blood urea nitrogen (BUN), fractional excretion of sodium (FENa), creatinine clearance rate (CCr) and Bcl2-associated X protein (Bax) expression. Results: IR significantly increased serum Cr (p< 0.01) and BUN levels (p< 0.01), elevated FENa (p<0.01) and tissue MDA (p<0.01), and decreased CCr (p< 0.01) and induced histological damage. Bax pro-apoptotic protein was upregulated in renal tissue after I/R injury and downregulated in simvastatin pretreated group. Simvastatin at doses of 10 and 20mg/kg/day significantly reduced serum Cr and BUN levels (p< 0.05 vs. IR group), tissue MDA contents and FENa (p< 0.05 vs. I/R) and increased CCr (p< 0.05 vs. IR). Renal tissue injury was improved only in simvastatin 20mg/kg/day group (p< 0.05). Glibenclamide significantly abolished protective effects of simvastatin and increased serum Cr and BUN and FENa and decreased CCr (p< 0.05). It also abolished the effects of simvastatin on tissue injury and MDA contents and downregulated the Bax protein after IR injury (p< 0.05). Conclusion: Opening of KATP channels is essential for simvastatin-induced renal protection against I/R injury

Dynamic ‘Spot Sign’ Resolution following INR Correction in a Patient with Warfarin-Associated Intracerebral Hemorrhage

Hematoma expansion in intracerebral hemorrhage is associated with poor clinical outcome. The ‘spot sign’ is a radiological marker that is associated with hematoma expansion, and thought to represent active extravasation of contrast. This case demonstrates the use of dynamic CT angiography in identifying the time-dependent appearance of a spot sign in a patient with warfarin-associated intracerebral hemorrhage. Repeat imaging is also presented which verified cessation of the spot sign after INR correction

Psoriasis & Comorbidities: Unraveling the Maze

__Abstract__ In this thesis we used a multifaceted approach to analyzing depression in psoriasis, by investigating Health Related Quality of Life (HRQoL), depressive symptoms, clinical depression and antidepressant use, using various data sources and statistical methods. These include a cross-sectional study, two population-based cohorts and a systematic review of the literature incorporated into a meta-analysis. A total of 40% of psoriasis patients from dermatological outpatient clinics in Belgium reported a substantial impact of psoriasis on their lives according to dermatology specific questionnaires. The level of generic impairment of the quality of life was comparable to the level observed in other chronic diseases such as asthma, diabetes and rheumatoid arthritis and also comparable to the level found in prostate cancer patients and patients with hematological malignancies. Patients with moderate to severe disease reported higher quality of life scores than those with milder disease, regardless of whether dermatology specific or generic instruments were used. According to a systematic review and meta-analysis of the literature on depression in psoriasis, one quarter of psoriasis patients manifest depressive symptoms and 12% are diagnosed with clinical depression. Psoriasis patients are one and a half times more likely to manifest signs of clinical depression compared with their healthy peers. Depressive symptoms in psoriasis were assessed in mostly small studies based in tertiary centers. The relationship between psoriasis and clinical depression was investigated in large population-based studies using administrative databases. The actual prevalence of depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria is hard to estimate due to the scarcity of available studies. However it is definitely lower than the prevalence of depressive symptoms. This difference was also noted in the population-based Rotterdam Study, where we demonstrated that symptoms of depression assessed according to the Center for Epidemiologic Studies Depression Scale (CES-D) >16 were manifest in 8.5% of 236 psoriasis patients, however when the patients with an elevated CES-D score underwent clinical examination by the psychiatrist, only 3 patients were diagnosed with a major or minor depression according to the DSM-IV. According to the meta-analysis we conducted, the overall pooled antidepressant use in psoriasis in the literature was 9% (6-14%). Data on drug dispenses from the Dutch pharmacy database showed that psoriasis patients were one and a half times more likely to use an antidepressant compared to the reference group (after adjustment for age, gender and general healthcare consumption). The use of antidepressant medication peaked when patients sought medical care for their psoriasis and thereafter. The effect of this increased healthcare seeking behavior was also reflected in the results from the Dutch General Practitioner (GP) database which show that psoriasis patients use significantly more medication of all therapeutic groups than patients without psoriasis of the same gender, age and GP practice. Patients with moderate to severe psoriasis had more prescriptions for medication compared to patients with mild disease. In the Dutch GP database the odds of antidepressant use was 1.35, 95%CI 1.26-1.45 in psoriasis patients compared to controls without psoriasis, which is in in the range of the results from the data we obtained from the Dutch pharmacy database (OR 1.47, 95% 1.43-1.51), with a dose-response for patients with moderate to severe disease in both studies

Spatial analysis of lipids in tissue samples applying mass spectrometry imaging

Lipids are important naturally occurring components in all living cellular organisms. They serve as the main building blocks of cellular membranes, participate in many signaling pathways and are also stored as an energy source. Due to the extreme complex cellular chemistry and structure of lipids, there is a real need to have a label-free technique with high chemical specificity, high accuracy and high sensitivity for study of lipids within the cell membrane. Mass spectrometry imaging (MSI) is capable of providing information on the chemical composition and spatial distribution of complex biological molecules. MSI is a powerful label-free tool for lipid analysis across biological materials. Both matrix-assisted laser desorption/ionization (MALDI) and secondary ion mass spectrometry (SIMS), the two most common MSI techniques, have recently undergone many developments to improve spatial resolution and provide high sensitivity, mainly for higher mass species. These two techniques offer different capabilities in the analysis of a biological system. The main differences are that larger molecules can be ionized and detected using MALDI, whereas SIMS is capable of detecting mainly small molecules but at higher spatial resolution compared to MALDI. This thesis mainly focuses on two scopes of investigation with different sample modifications and also on the overall applicability of MSI for analysis of tissue samples. In recent years, some surface modifications have been developed to enhance the yield of intact molecular species in SIMS. One of them is matrix enhancement secondary ion mass spectrometry (ME-SIMS), which is the combination of the protocol for MALDI sample preparation and normal SIMS. In paper I, the possible mechanism of the signal enhancement in ME-SIMS was studied. Here, sublimation was used to deposit a thin layer of an organic matrix on the surface of a brain tissue slice analyzed with SIMS. In this work, I showed that sublimation could successfully provide enhancement in ion yields for a multitude of lipid species in SIMS. The mechanism of this enhancement could be due to a lower ion suppression followed by removal of the cholesterol crystals from the surface of sample allowing detection for less abundant species. It is also possible that the extraction of some specific lipids into the deposited matrix directly leads to an increase of higher mass lipid ion yield. In paper II, two different surface modifications, including matrix sublimation and nanoparticle deposition were applied on Drosophila brain samples and lipid information obtained from MALDI analysis were compared. Here, it was shown that each technique can be used in a complementary approach to detect a variety of lipid species. In paper III, SIMS imaging was employed to investigate the effect of specially processed cereals, as a specific diet on the alteration of lipid composition across the rodent intestine tissue. In paper IV, I continued the study of changes in lipid content, this time on brain samples of animals exposed to the same diet. Intake of such cereals increases active antisecretory factor (AF) in plasma, an endogenous protein with proven regulatory function on inflammation and fluid secretion. Although, the exact mechanism for the activation process of AF at the cellular level remains unclear. The results show changes in lipid content of cell membrane in response to this cereals intake suggesting a relation to activating AF. In paper V, the techniques for developing of sample preparation in SIMS imaging were investigated to improve the signal intensity of intact molecules at higher resolution

Prevalence and associated factors of viral hepatitis and transferrin elevations in 5036 patients admitted to the emergency room of a Swiss university hospital: cross-sectional study

BACKGROUND: The epidemiology of liver disease in patients admitted to emergency rooms is largely unknown. The current study aimed to measure the prevalence of viral hepatitis B and C infection and pathological laboratory values of liver disease in such a population, and to study factors associated with these measurements. METHODS: Cross-sectional study in patients admitted to the emergency room of a university hospital. No formal exclusion criteria. Determination of anti-HBs, anti-HCV, transferrin saturation, alanine aminotransferase, and obtaining answers from a study-specific questionnaire. RESULTS: The study included 5'036 patients, representing a 14.9% sample of the target population during the study period. Prevalence of anti-HBc and anti-HCV was 6.7% (95%CI 6.0% to 7.4%) and 2.7% (2.3% to 3.2%), respectively. Factors independently associated with positive anti-HBc were intravenous drug abuse (OR 18.3; 11.3 to 29.7), foreign country of birth (3.4; 2.6 to 4.4), non-white ethnicity (2.7; 1.9 to 3.8) and age > or =60 (2.0; 1.5 to 2.8). Positive anti-HCV was associated with intravenous drug abuse (78.9; 43.4 to 143.6), blood transfusion (1.7; 1.1 to 2.8) and abdominal pain (2.7; 1.5 to 4.8). 75% of all participants were not vaccinated against hepatitis B or did not know their vaccination status. Among anti-HCV positive patients only 49% knew about their infection and 51% reported regular alcohol consumption. Transferrin saturation was elevated in 3.3% and was associated with fatigue (prevalence ratio 1.9; 1.2 to 2.8). CONCLUSION: Emergency rooms should be considered as targets for public health programs that encourage vaccination, patient education and screening of high-risk patients for liver disease with subsequent referral for treatment if indicated