The effect of bradykinin and its antagonist on survival time after coronary artery occlusion in hypertensive rats

It is known that BK does play a role in the cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors. The present study therefore was conducted to examine the effects of bradykinin (BK) and its antagonist on survival time in spontaneously hypertensive rats (SHR) with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure (BP) in the presence and absence of BK and BK2 receptor antagonist, D-Arg-[Hyp-D-Phe7]BK. Coronary artery was ligated in anaesthetized rats and they were artificially ventilated with room air (stroke volume, 4 ml; 48 strokes/min) as described by the previous investigators. Lead II elecrocardiogram (ECG) was recorded from subcutaneous steel needle electrodes. Results of this investigation indicated that BK treatment 4 microg/kg (i.v.) and 8 microg/kg (i.v.) caused significant (P < 0.05) increase in survival time in SHR with coronary artery ligation for 15 min and continuously as compare to their respective saline-treated controls. However, BK antagonist treatment 4 microg/kg (i.v.) abolished the increase in survival time caused by BK treatment. The mean values of survival time between the saline-treated and BK antagonist plus BK-treated rats did not differ significantly (P > 0.05). The heart rate and BP responses were greatly reduced (P < 0.001) in the presence of coronary artery ligation. These findings suggest that BK might have cardioprotective effect to increase the survival time in rats by activating BK2 receptors after coronary artery ligation.     

Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy- 11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography. The major adduct was identified as a product of the reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose- dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-->G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.      

TREATMENT OF PALMOPLANTER HYPERHIDROSIS BY IONTOPHORESIS

Twenty-seven patients with idiopathic palmoplanter hyperhidrosis were treated with Iontotherapy over a one year period. In twenty-four cases there was a good response but maintenance therapy was required every 3-4 weeks.KEY WORDS: Iontophoresis, Palmoplanter hyperhidrosis     

Anxiety and depression levels of healthcare workers during Covid-19 pandemic

BackgroundCoronavirus disease 2019 (covid-19), which causes a pandemic in the world, has started to appear in turkey since march 2020. Healthcare workers are at the top of the groups most at risk for covid-19 infection, which can have a negative impact on psychological state.ObjectivesIt was aimed to evaluate anxiety and depression levels among healthcare workers.Methodsthis cross-sectional study performed via an online survey in april 2020. Participants answered questions about sociodemographic features, personal views and experiences about covid-19 and the hospital anxiety and depression scale (hads).ResultsA total of 300 healthcare workers,193 men and 107 women, participated in the survey. According to hads, 44.6% of participants scored above anxiety and 68.2% scored above depression cut-off points. Being younger than 50 and taking care of covid-19 patients in hospitals were independently associated with anxiety risk. Female gender, young age (less than 50) and having comorbidity were independent risk factors for depression.ConclusionHealthcare workers were at high risk of anxiety and depression during covid-19 outbreak. For this reason, psychological support should be given, especially to the group with high risk.     

Ermin deficiency leads to compromised myelin,inflammatory milieu,and susceptibility to demyelinating insult

Ermin is an actin‐binding protein found almost exclusively in the central nervous system (CNS) as a component of myelin sheaths. Although Ermin has been predicted to play a role in the formation and stability of myelin sheaths, this has not been directly examined in vivo. Here, we show that Ermin is essential for myelin sheath integrity and normal saltatory conduction. Loss of Ermin in mice caused de‐compacted and fragmented myelin sheaths and led to slower conduction along with progressive neurological deficits. RNA sequencing of the corpus callosum, the largest white matter structure in the CNS, pointed to inflammatory activation in aged Ermin‐deficient mice, which was corroborated by increased levels of microgliosis and astrogliosis. The inflammatory milieu and myelin abnormalities were further associated with increased susceptibility to immune‐mediated demyelination insult in Ermin knockout mice. Supporting a possible role of Ermin deficiency in inflammatory white matter disorders, a rare inactivating mutation in the ERMN gene was identified in multiple sclerosis patients. Our findings demonstrate a critical role for Ermin in maintaining myelin integrity. Given its near‐exclusive expression in myelinating oligodendrocytes, Ermin deficiency represents a compelling “inside‐out” model of inflammatory dysmyelination and may offer a new paradigm for the development of myelin stability‐targeted therapies.