ROS quenching potential of the epidermal cornified cell envelope

The cornified cell envelope (CE) is a specialized structure assembled beneath the plasma membrane of keratinocytes in the outermost layers of the epidermis. It is essential for the physical and permeability properties of the barrier function of the skin. Our skin is continuously exposed to atmospheric oxygen and threatened by reactive oxygen species (ROS). Here, we identify the CE as a first line of antioxidant defense and show that the small proline-rich (SPRR) family of CE precursor proteins have a major role in ROS detoxification. Cysteine residues within these proteins are responsible for ROS quenching, resulting in inter- and intramolecular S-S bond formation, both in isolated proteins and purified CEs. The related keratinocyte proline-rich protein is also oxidized on several cysteine residues within the CE. Differences in antioxidant potential between various SPRR family members are likely determined by structural differences rather than by the amount of cysteine residues per protein. Loricrin, a major component of the CE with a higher cysteine content than SPRRs, is a weak ROS quencher and oxidized on a single cysteine residue within the CE. It is inferred that SPRR proteins provide the outermost layer of our skin with a highly adaptive and protective antioxidant shield.     

Simulating influenza epidemics with waning vaccine immunity

Observational studies indicate that vaccine-induced immunity can decline over time. However, few researchers have incorporated this kind of waning effect into their virus spread models. In this study, we simulate an influenza epidemic that considers the effects of waning immunity by fitting epidemiological models to CDC secondary historical data aggregated on a weekly basis, and derive the transmission rates at which susceptible individuals become infected over the course of the influenza season. Using a system of differential equations, we define four groups of individuals in a population: susceptible, vaccinated, infected, and recovered. We show that a larger number of initially infected individuals might not only bring the influenza season to an end sooner but also reduce the epidemic size. Moreover, any influenza virus that entails a faster recovery rate does not necessarily lead to a smaller epidemic size. We illustrate how simulation helps in understanding the effects of influenza epidemiological model in the presence of waning influenza vaccine immunity.     

Does CMR have an additive role over echo in evaluating ischemic LV dysfunction?

Purpose

To emphasis the role of cardiac magnetic resonance compared to echocardiography in evaluating patients with ischemic cardiomyopathy to accurately assess global and regional Left ventricular function which is essential for prognosis and for evaluating therapeutic responses.

Methods and materials

The studied group included 37 patients already diagnosed as having ischemic cardiomyopathy. All patients were subjected to full history taking and radiological evaluation using a 1.5-T MR system and echocardiography. Comparison was made between echocardiography and cardiac magnetic resonance regarding segmental wall motion by using the 17-segment model of the American Heart Association. Agreement regarding segmental wall motion was assessed by using Cohen’s Kappa statistics. Also ejection fraction measurement by both modalities was compared. Detection of transmural extent of myocardial scar was also performed.

Results

Poor agreement between cardiac magnetic resonance and echocardiography regarding segmental wall motion with Cohen’s Kappa is 0.195, P value of <0.001. Mean ejection fraction by cardiac magnetic resonance was 33.3% and mean ejection fraction by echocardiography was 29% with a mean difference of 4.3%.

Conclusion

Cardiac magnetic resonance is superior to echo in evaluating segmental wall motion abnormality with echo underestimating segmental wall motion abnormality yet nearly similar ejection fraction values by both modalities were achieved. Moreover, cardiac magnetic resonance is better in evaluating associated cardiac abnormalities as well as extracardiac findings due to its higher spatial resolution. In addition, cardiac magnetic resonance is used in myocardial viability assessment in the same setting which if combined with segmental wall motion abnormality can lend a hand in evaluating the cardiac contractile reserve.     

Relation of Nickel Allergy with in-Stent Restenosis in Patients Treated with Cobalt Chromium Stents

Background

In-stent restenosis (ISR) is the major limitation of percutaneous coronary stenting procedure. The elements like nickel, chromate and molybdenum are known to cause contact allergy. Hypersensitivity reaction, against these metal ions, may be one of the reasons of ISR. Cobalt chromium coronary stents, which are increasingly being used in percutaneous coronary interventions, have more nickel amount than the stainless steel stents.

Objective

We aimed to investigate the association between nickel hypersensitivity reaction and ISR in patients treated with cobalt chromium coronary stents.

Methods

Epicutaneous patch tests for nickel were applied to 31 patients who had undergone elective cobalt chromium coronary stent implantation and had ISR in control angiogram. Thirty patients, without ISR, were included as the control group. Patch test results and other clinical variables were compared.

Results

There was no statistically significant difference of the mean age, sex, body mass index, rate of hypercholesterolemia, diabetes, hypertension and smoking between the patients with and without ISR. All other lesion characteristics were similar in the 2 groups. According to the patch test results, 7 patients had nickel contact allergy. All of these patients were in the ISR group, which was statistically significant (p<0.006).

Conclusion

Patients treated with cobalt chromium coronary stents and had ISR were found to have significantly more nickel allergy than the control group. Nickel allergy may play role in restenosis pathophysiology.     

DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex

Activation of delta-opioid receptors (DOR) is neuroprotective against hypoxic/ischemic injury in the cortex, which is at least partially related to its action against hypoxic/ischemic disruption of ionic homeostasis that triggers neuronal injury. Na(+) influx through TTX-sensitive voltage-gated Na(+) channels may be a main mechanism for hypoxia-induced disruption of K(+) homeostasis, with DOR activation attenuating the disruption of ionic homeostasis by targeting voltage-gated Na(+) channels. In the present study we examined the role of DOR in the regulation of Na(+) influx in anoxia and simulated ischemia (oxygen-glucose deprivation) as well as the effect of DOR activation on the Na(+) influx induced by a Na(+) channel opener without anoxic/ischemic stress and explored a potential PKC mechanism underlying the DOR action. We directly measured extracellular Na(+) activity in mouse cortical slices with Na(+) selective electrodes and found that (1) anoxia-induced Na(+) influx occurred mainly through TTX-sensitive Na(+) channels; (2) DOR activation inhibited the anoxia/ischemia-induced Na(+) influx; (3) veratridine, a Na(+) channel opener, enhanced the anoxia-induced Na(+) influx; this could be attenuated by DOR activation; (4) DOR activation did not reduce the anoxia-induced Na(+) influx in the presence of chelerythrine, a broad-spectrum PKC blocker; and (5) DOR effects were blocked by PKCβII peptide inhibitor, and PKCθ pseudosubstrate inhibitor, respectively. We conclude that DOR activation inhibits anoxia-induced Na(+) influx through Na(+) channels via PKC (especially PKCβII and PKCθ isoforms) dependent mechanisms in the cortex.     

Rapidly developing giant sized lupus vulgaris on the chest associated with bilateral scrofuloderma on the neck

Lupus vulgaris and scrofuloderma are the opposite poles of cutaneous tuberculosis. Lupus vulgaris of a giant size and scrofuloderma in the vicinity of this lesion were both present in a 70-year-old female patient. The purified protein derivative of tuberculin (PPD) skin test was strongly positive. In histopathological examination, granulomatous infiltration without caseation necrosis was seen in the dermis. The patient was treated with a four-drug therapy consisting of pyrazinamide (25 mg/kg), isoniazid (5 mg/kg), rifampin (10 mg/kg) and ethambutol (15 mg/kg) daily for 2 months, followed by dual therapy with isoniazid and rifampin for 6 months. Her cutaneous lesions significantly regressed after 4 months, leaving keloid scars.