Autochthonous Case of Rickettsia slovaca Infection in Russia

We describe an autochthonous case of Rickettsia slovaca infection in a man 35 years of age from Russia who had tickborne lymphadenopathy. We used ELISA and quantitative PCR testing to further identify DNA and confirm diagnosis. Physicians in Russia should consider similar diseases in differential diagnoses after tick bites.     

Impact of expanded access to combination antiretroviral therapy in pregnancy: results from a cohort study in Ukraine

Objective

To investigate the scale-up of antenatal combination antiretroviral therapy (cART) in Ukraine since this became part of the national policy for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV).

Methods

Data on 3535 HIV-positive pregnant women who were enrolled into the Ukraine European Collaborative Study in 2008–2010 were analysed. Factors associated with receipt of zidovudine monotherapy (AZTm) – rather than cART – and rates of mother-to-child transmission (MTCT) of HIV were investigated.

Findings

cART coverage increased significantly, from 22% of deliveries in 2008 to 61% of those in 2010. After adjusting for possible confounders, initiation of antenatal AZTm – rather than cART – was associated with cohabiting (versus being married; adjusted prevalence ratio, aPR: 1.09; 95% confidence interval, CI: 1.02–1.16), at least two previous live births (versus none; aPR: 1.22; 95% CI: 1.11–1.35) and a diagnosis of HIV infection during the first or second trimester (versus before pregnancy; aPR: 1.11; 95% CI: 1.03–1.20). The overall MTCT rate was 4.1% (95% CI: 3.4–4.9); 42% (49/116) of the transmissions were from the 8% (n = 238) of women without antenatal ART. Compared with AZTm, cART was associated with a 70% greater reduction in the risk of MTCT (adjusted odds ratio: 0.30; 95% CI: 0.16–0.56).

Conclusion

Between 2008 and 2010, access to antenatal cART improved substantially in Ukraine, but implementation of the World Health Organization’s Option-B policy was slow. For MTCT to be eliminated in Ukraine, improvements in the retention of women in HIV care and further roll-out of Option B are urgently needed.     

How technology is transforming the ways in which children play

Technology is a prominent way that young children choose to play. With new advents in technology, children are finding it easier to gain access to technology through parents’ cell phones and tablets. The influx of technology in the daily lives of children is putting into question whether or not children are spending too much time engaging in such play. In the current study, data were collected on how 3–5-year-old children played on a typical weekday and weekend. Of the weekday activities, parents (n?=?31) reported 53.00 hours of technology play for an average of 1.71 hours per child per day. There was an increased amount of time spent on non-technology activities listed by parents for a total of 59.25 hours and an average of 1.91 hours per child. A smaller number of parents (n?=?14) recorded outdoor play, totalling 17.50 hours with an average of 1.25 hours per child.     

Effects of fluorine-containing opener of ATP-sensitive potassium channels, pinacidil-derivative flocalin, on cardiac voltage-gated sodium and calcium channels

Fluorine-containing pinacidil-derivative flocalin is an effective adenosine triphosphate-sensitive potassium (K_ATP)-channel opener with pronounced vasodilatory, cardioprotective effects and low general toxicity. By activating cardiac K_ATP channels, flocalin hyperpolarizes cardiac myocytes, decreases their excitability, reduces Ca²⁺ entry, and inhibits Ca²⁺-dependent signalling processes. Since our previous studies indicated that the drug also influences the rate of rise and amplitude of the cardiomyocyte’s action potential, here we have investigated its possible actions on depolarizing inward currents through voltage-gated sodium (VGSC) and L-type calcium (VGCC) channels. Experiments were conducted on cultured cardiac myocytes prepared from the whole hearts of neonatal rats and maintained in culture for 1–3?days using whole-cell patch-clamp technique with no distinction of myocyte’s type. Flocalin concentration dependently inhibited the Na⁺ inward current through VGSCs with IC₅₀?=?17.4?μM and a maximal extent of 0.54, slowed down its inactivation kinetics, and hyperpolarized steady-state inactivation by 5.6?mV. The drug also inhibited calcium current through L-type VGCCs with IC₅₀?=?24.1?μM and a maximal block of 0.38, without affecting its inactivation but producing 5.3-mV hyperpolarization shifting of steady-state activation. Inhibition of both depolarizing currents by flocalin in addition to its ability to open K_ATP channels enhances the suppressive action of the drug on cardiac excitability and broadens its pharmacological effects. Since, according to our previous data, cardiac K_ATP-channel opening by flocalin occurs with ЕC₅₀?=?8?μM, the possibility of partial blockade of VGSC and L-type VGCCs should be considered when determining the therapeutic concentrations of the compound during its use as a cardioprotector.     

Effects of angiotensin receptor blockers on endothelial nitric oxide release: the role of eNOS variants

AIM

Angiotensin II receptor blockers (ARBs) improve endothelial cell (EC)-dependent vasodilation in patients with hypertension through suppression of angiotensin II type 1 receptors but may have additional and differential effects on endothelial nitric oxide (NO) synthase (eNOS) function. To investigate this question, we tested the effects of various ARBs on NO release in ECs from multiple donors, including those with eNOS genetic variants linked to higher cardiovascular risk.

METHODS

The effects of ARBs (losartan, olmesartan, telmisartan, valsartan), at 1 µm, on NO release were measured with nanosensors in human umbilical vein ECs obtained from 18 donors. NO release was stimulated with calcium ionophore (1 µm) and its maximal concentration was correlated with eNOS variants. The eNOS variants were determined by a single nucleotide polymorphism in the promoter region (T-786C) and in the exon 7 (G894T), linked to changes in NO metabolism.

RESULTS

All of the ARBs caused an increase in NO release as compared with untreated samples (P < 0.01, n = 4–5 in all eNOS variants). However, maximal NO production was differentially influenced by eNOS genotype. Olmesartan increased maximal NO release by 30%, which was significantly greater (P < 0.01, n = 4–5 in all eNOS variants) than increases observed with other ARBs.

CONCLUSIONS

The ARBs differentially enhanced NO release in ECs in a manner influenced by eNOS single nucleotide polymorphisms. These findings provide new insights into the effects of ARBs on EC-dependent vasodilation and eNOS function.     

Prostaglandin-secreting cells: a portable first aid kit for tissue repair

After intestinal injury, both the number and type of intestinal epithelial cells must be restored. Intestinal stem cells, located at the base of the intestinal crypt, repopulate the depleted crypt in a process known as compensatory proliferation. In this issue of the JCI, Brown et al. describe a new mechanism by which this process is regulated (see the related article beginning on page 258). Surprisingly, they find that a subset of stromal cells present within the intestinal tissue and expressing the proliferative factor prostaglandin-endoperoxidase synthase 2 (Ptgs2) is repositioned next to the intestinal stem cell compartment where local production of PGE(2) controls injury-induced epithelial cell proliferation.     

The effects of PTK787/ZK222584, an inhibitor of VEGFR and PDGFRβ pathways, on intussusceptive angiogenesis and glomerular recovery from Thy1.1 nephritis

The aim of our study was to investigate the phenomenon of intussusceptive angiogenesis with a focus on its molecular regulation by vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor β (PDGFRβ) pathways and biological significance for glomerular recovery after acute injury. Glomerular healing by intussusception was examined in a particular setting of Thy1.1 nephritis, where the lysis of mesangial cells results in an initial collapse and successive rebuilding of glomerular capillary structure. Restoration of capillary structure after induction of Thy1.1 nephritis occurred by intussusceptive angiogenesis resulting in i) rapid expansion of the capillary plexus with reinstatement of the glomerular filtration surface and ii) restoration of the archetypical glomerular vascular pattern. Glomerular capillaries of nephritic rats after combined VEGFR2 and PDGFRβ inhibition by PTK787/ZK222584 (PTK/ZK) were tortuous and irregular. However, the onset of intussusceptive angiogenesis was influenced only after long-term PTK/ZK treatment, providing an important insight into differential molecular regulation between sprouting and intussusceptive angiogenesis. PTK/ZK treatment abolished α-smooth muscle actin and tensin expression by injured mesangial cells, impaired glomerular filtration of microspheres, and led to the reduction of glomerular volume and the presence of multiple hemorrhages detectable in the tubular system. Collectively, treatment of nephritic patients with PTK/ZK compound is not recommended.     

Spinal intramedullary cavernous hemangioma

The spinal cord can be involved in a variety of disease processes. These can be congenital or acquired. An acute onset of symptoms usually allows a defined set of causes to be considered including trauma, ruptured vascular anomalies, demyelination, and myelitis. Intramedullary cavernous hemangioma of the spinal cord is a congenital or acquired vascular malformation, and one of the rare causes of hematomyelia. We present such a case, and discuss the symptoms, diagnosis, and suggested best treatment options based on a review of present day literature.