Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy

Polyomavirus BK (BKV) is the cause of polyomavirus‐associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.     

THe effect of γ,γ-BIS-4-ethylphenyl-α, β-dibromoisocrotonic acid on ehrlich ascites carcinoma and yeast cells

In Ehrlich ascites carcinoma (EAC) cells γ,γ-bis-4-ethylphenyl-α,β-dibromoisocrotonic acid (EPBC) inhibits after short exposure the incorporation of [¹⁴C]valine. [¹⁴C]adenine and [¹⁴C]thymicline, the rate of inhibition being directly related to the concentration of the inhibitor. This inhibition occurs even at concentrations of EPBC which stimulate the endogeneous respiration of the cells as well as the consumption of glucose and the formation of lactate. Higher concentrations fully depress the endogeneous respiration and glycolysis and cause loss of transplantability of EAC cells. The attack on glycolysis is multitarget in character. The activities of several enzymes dependent on free sulfhydryl groups, especially glyceraldehyde-3-phosphate dehydrogenase, glucosc-6-phosphatc dehydrogenase and phosphofructokinase, are inhibited by EPBC. The changes in the total sulfhydryl group content and other findings suggest the existence of direct chemical reaction of EPBC with thiol groups. The same mechanism may explain also the effect of EPBC on glycolysis in yeast cells.     

Eosinophilia, mast cell hyperplasia and antibody production in rats following an intraperitoneal injection of Ascaris cuticle including in-vitro studies of immune eosinophil granule lysis

A single intraperitoneal injection of Ascaris cuticle caused a local eosinophilia with peak levels at 2 wk after injection. Mast cells reduced in number and size at 1 wk were found in increased numbers at 3 wk. Injection of a collagen-poor fraction of cuticle known as "cuticlin" resulted in a diminished eosinophil and mast cell response compared with injection of whole cuticle. Precipitating antibodies to soluble Ascaris cuticle collagen were detected in the serum and peritoneal fluid from day 5 onward. It is proposed that the eosinophilia and mast cell hyperplasia are the result of immunization of the animal to an antigen present in Ascaris collagen and rendered soluble by the action of mononuclear phagocytes. The eosinophil and mast cell response to Ascaris cuticle mimicked the response in connective tissue to living nematode parasites. It is concluded that the cuticle of nematode parasites may be responsible for eosinophilia and mast cell hyperplasia in the host.     

Fourier analysis of the nerve fiber layer by digital imaging techniques

We introduce a new method to examine the retinal nerve fiber layer (RNFL) that may detect early changes in its structure due to glaucoma. Viewed in the conventional manner, in a plane perpendicular to the retina, we get an estimation of the structural integrity of the RNFL. Viewed from a plane parallel to the retina, the RNFL forms a contour surface of hills and valleys. In our method red free fundus slides are digitally acquired. A waveform, representing a topographic profile cut through the resulting representation of the RNFL contour surface, was analyzed using Fourier's transform. Three cycles/mm in the Fourier power spectrum was used as an arbitrary cutoff to discriminate normal from glaucomatous RNFL. The Fourier power spectrum from normal RNFL was shifted to higher spatial frequencies, while the power spectrum from glaucomatous RNFL was shifted to lower spatial frequencies. Thus, Fourier Analysis can reveal information about such a wave form which is not obvious by visual inspection or by densitometric techniques. This method may allow for an even earlier diagnosis of injury to the optic nerve due to glaucoma.     

Genotoxic risk of Goeckerman's therapy of psoriasis. Pilot study--children

Goeckerman's therapy of psoriasis includes combined exposure to therapeutic tar and UV-B radiation. In a pilot study of (12 children) a level of genotoxic risk of the therapy was evaluated by chromosomal aberration of peripheral lymphocytes. Results of the pilot study suggest possible genotoxic risk of the therapy.     

Influence of tobacco use in dental caries development

This review article describes different forms of tobacco usage and its direct relationship with the prevalence of dental caries. Smoking along with co-existing factors like old age, bad oral hygiene habits, food habits, limited preventive dental visits and over all health standards, can be associated with high caries incidence. However, a direct etiological relationship is lacking. Environmental tobacco smoke (ETS) causes dental caries in children but no studies have been reported in adults. Existing findings are not sufficient and conclusive enough to confirm that ETS causes dental caries. Oral use of smokeless tobacco (ST), predominantly tobacco chewing, is presumably a positive contributing factor to higher incidence of dental caries. Unfortunately, published studies are not converging towards one single factor through which tobacco usage can have direct relationship to dental caries.     

Association analysis of two tyrosine hydroxylase gene polymorphisms in normotensive offspring from hypertensive families

Objective: We have studied possible association between predisposition to essential hypertension, plasma noradrenaline level and two polymorphisms of the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. Design and Methods: One hundred and one normotensive sons from normotensive parents (SN) and 107 normotensive sons of hypertensive families (SH) were studied. Tetranucleotide TCAT repeat and Val81Met polymorphisms of the TH gene were determined by polymerase chain reaction (PCR) technique. Results: SH had higher systolic BP and plasma noradrenaline concentration than the SN group. No significant difference was found between the allele and genotype frequencies in the SH and SN groups for both polymorphisms. The two polymorphisms were in tight linkage disequilibrium. The CD genotype of the microsatellite marker was associated with increased plasma noradrenaline concentration in both groups. Genotypes AB, AE and BB of the TCAT repeat polymorphism and genotypes VM and MM of the Val81Met polymorphism exhibited the greatest difference in plasma noradrenaline concentration between the SH and SN groups. Conclusion: The studied TH polymorphisms do not appear to be associated with family history of essential hypertension. Nevertheless, some genotypes of TH might be related to disturbance of plasma noradrenaline concentration.