Effects of long-term treatment in Wilson's disease withd-penicillamine and zinc sulphate

The results of treatment withd-penicillamine (d-P) or zinc sulphate (Zn) in 67 newly diagnosed cases of Wilson's disease have been compared. All patients (7 with hepatic, 1 with psychiatric and 59 with neurological or preclinical forms) were fully compliant. During 12 years of observation, 34 patients receivedd-P and 33 Zn as the primary treatment. Fifteen patients (44%) discontinuedd-P, in 10 cases owing to side effects. Four (12%) patients discontinued Zn, in 2 cases because of side-effects. One patient who received Zn deteriorated during the first few months after the initiation of therapy. The effectiveness of longterm treatment withd-P and Zn was similar in those patients who were able to continue the initial therapy. Zn was tolerated better thand-P; we suggest, therefore, that it may be recommended as an initial therapy for patients in the preclinical stage of Wilson's disease or with neurological presentation of the disease. More observation is needed for patients with the hepatic and psychiatric forms of the disease.     

Evolution of Helicobacter pylori susceptibility to antibiotics during a 10‐year period in Lithuania

The study evaluated the changes in the prevalence of Helicobacter pylori strains with primary resistance to antibiotics during the last 10 years in Lithuania. H. pylori susceptibilities to antibiotics were tested in 89 patients in 1998, in 81 patients in 2001 and in 90 patients in 2007/2008. Susceptibility to metronidazole, clarithromycin, amoxicillin and tetracycline was tested using E‐test or agar dilution method. Susceptibility to ciprofloxacin was only tested in 2007/2008. Data about utilization of all authorized and available on market macrolides and clindamycin in Lithuania during 2003–2007 were evaluated using WHO ATC/DDD methodology. A total of 260 H. pylori strains cultured from untreated adult patients were investigated. Primary resistance rates (1998, 2001 and 2007/2008) for metronidazole were 24.7%, 33.3%, and 35.6%, for clarithromycin 1.1%, 3.7%, and 3.3% and for tetracycline 0%, 2.5% and 0% respectively. No cases of amoxicillin resistance have been detected. The resistance rate for ciprofloxacin was 5.6% in 2007/2008. Data of total macrolides and clarithromycin utilization in Lithuania revealed that despite an increase of consumption of these drugs in Lithuania during 2003–2007 in 1.5 times, the total macrolide consumption remains one of the lowest in Europe. We have not observed any significant changes in the susceptibility of H. pylori to the most widely used antibiotics during the recent 10‐year period. The low resistance rate to clarithromycin might be related to the policy to avoid use of macrolides as first‐line treatment for pulmonary and other infections.     

Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase

Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47^phox subunits, elevated level of p47^phox phosphorylation, and enlarged phospho‐p47^phox and p67^phox content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho‐p47^phox and p67^phox. Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.     

Orexins Protect Neuronal Cell Cultures Against Hypoxic Stress: an Involvement of Akt Signaling

Orexins A and B are peptides produced mainly by hypothalamic neurons that project to numerous brain structures. We have previously demonstrated that rat cortical neurons express both types of orexin receptors, and their activation by orexins initiates different intracellular signals. The present study aimed to determine the effect of orexins on the Akt kinase activation in the rat neuronal cultures and the significance of that response in neurons subjected to hypoxic stress. We report the first evidence that orexins A and B stimulated Akt in cortical neurons in a concentration- and time-dependent manner. Orexin B more potently than orexin A increased Akt phosphorylation, but the maximal effect of both peptides on the kinase activation was very similar. Next, cultured cortical neurons were challenged with cobalt chloride, an inducer of reactive oxygen species and hypoxia-mediated signaling pathways. Under conditions of chemical hypoxia, orexins potently increased neuronal viability and protected cortical neurons against oxidative stress. Our results also indicate that Akt kinase plays an important role in the pro-survival effects of orexins in neurons, which implies a possible mechanism of the orexin-induced neuroprotection.     

Digital analysis yields more reliable and accurate measures of dermal and epidermal thickness in histologically processed specimens compared to traditional methods

Changes in the thickness of the dermis and epidermis have been described in the scenario of tissue expansion as well as inflammatory skin processes (psoriasis, contact hypersensitivity and so on). These changes have previously been quantified using ocular micrometers to obtain and then average a limited number of spot measurements, leading to suboptimal accuracy. We describe a rapid method of using freely available ImageJ software to analyze digitized images of fixed skin specimens. By determining the cross‐sectional area and surface length of a skin layer, a simple calculation produces more accurate and reproducible measurements of its thickness compared to historical methods, with excellent inter‐rater reliability.     

An Assessment of Dental Treatment Need: An Overview of Available Methods and Suggestions for a New, Comparative Summative Index

Objective: The aims were to give an overview and consider advantages and disadvantages of different approaches used to evaluate dental treatment need and to suggest an alternate Quantitative Summative Dental Treatment Need Index. Methods: The Medline Ovid database was searched for relevant articles published during the last three decades combining the terms "needs assessment,""dental care,""health services needs and demand." Results: There were substantial differences in methods used. Different modifications of the Decayed, Missing, Filled Teeth/Surfaces indices, complex quantitative summative indices, or simplified approaches were used to assess dental treatment need. Differing advantages and disadvantages of these methods can be identified. Previously used approaches have a common limitation for use in oral epidemiology. Conclusions: The suggested alternate Quantitative Summative Dental Treatment Needs Index focuses on an ability to compare both the total burden of treatment need as well as to make a distinction among specific treatment needs across populations. This new approach is an attempt to develop a comprehensive index for use in oral epidemiology with further revisions anticipated.