Usporedna učinkovitost eprinomektina i permetrina u liječenju sarkoptoze pasa.

The present study was conducted to evaluate the comparative efficacy of topically applied eprinomectin and permethrin for treatment of naturally occuring sarcoptic mange in dogs. A total of 24 dogs of various breeds, age and of both sexes were enrolled. Diagnosis of naturally occuring sarcoptic mange in dogs was made by identifying skin scrapings. All cases were subjected to scoring of the relevant significant clinical signs of scabies such as erythema, pruritis, alopecia, hyperpigmentation and crusting for the whole duration of the study. Dogs in group I (n = 9) received 0.5 mg/kg eprinomectin (5 mg/mL) topically once a week, and group II (n = 8) permethrin at a dosage of 20 mg/kg (100 mg/mL) topicallly once a week, both for a total of 4 weeks. Dogs in group III (n = 7) did not receive any treatment and were left as the control. All the scoring results were statistically evaluated on day 0 and 70, and revealed eprinomectin as the most effective group for evaluating clinical recovery (P<0.05). Evaluation of clinical signs and scoring results suggested complete clinical cure of 100% of dogs in the eprinomectin group, while permetrin was not effective where cure was evident in 2 out of 8 cases. In conclusion, topically applied eprinomectin was highly effective against naturally acquired infestation of S. scabieiby combined assessment of skin scrapings, scoring of skin lesions and clinical signs in comparison to permethrinIstraživanje je provedeno radi procjene usporedne učinkovitosti primjene eprinomektina i permetrina na koži u liječenju sarkoptoze pasa. Provedeno je na 24 psa različitih pasmina, dobi i spola. Bolest je dijagnosticirana na temelju nalaza parazita u strugotinama kože. Promatrani su klinički znakovi šuge poput crvenila, svrbeža, alopecije, hiperpigmentacije te pojave krasti. Psi u prvoj skupini (n = 9) liječeni su dozom od 0,5 mg (5 mg/mL) eprinomektina jednom tjedno. Permetrin je bio primijenjen u pasa druge skupine (n = 8) u dozi od 20 mg/kg (100 mg/mL) jednom tjedno. Liječenje je trajalo 4 tjedna. Psi u trećoj skupini (n = 7) nisu liječeni i služili su kao kontrola. Postignuti rezultati bili su statistički obrađeni uzimajući u obzir nalaze nultoga i sedamdesetoga dana. Rezultati su pokazali potpuno izlječenje u svih pasa u kojih je rabljen eprinomektin. Primjena permetrina bila je učinkovita u svega 2 od 8 slučajeva. Lokalna primjena eprinomektina bila je učinkovita kod prirodne infestacije grinjom Sarcoptes scabieišto se može zaključiti na osnovi pretraga strugotina kože, određivanja kožnih lezija i kliničkih znakova

The effect of the UPR and NMD mechanisms on the response to readthrough treatments

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Explaining the Frequency of Alcohol Consumption in a Conflict Zone: Jews and Palestinians in Israel

Experiencing stress and exposure to terrorism may have an adverse effect on health risk behaviors. Few studies have examined alcohol use among adults living in Israel under chronic, stressful terrorism-related conditions. In this study, we examined the relationships of demographics, past stressful events, and terrorism exposure to the frequency of alcohol use and the mediating roles of depressive and post-traumatic stress disorder (PTSD) symptoms. We used three waves of data from a 2007–2008 nationally representative sample of Jewish and Palestinian adults in Israel. We assessed past stressful events, in addition to direct and indirect exposures to terrorism. Results indicated that past stressful events and exposure to terrorism were not directly associated with alcohol use, but were indirectly associated and mediated by depressive and PTSD symptomology. Mental health symptoms were differentially associated with alcohol use. More frequent drinking was mediated by higher levels of depression, including for women and Palestinians; however, PTSD symptom severity was related to less frequent drinking. Mental health may play a prominent role in the frequency of alcohol use among adults exposed to terrorism in Israel. Alcohol use, as a coping mechanism, may differ by demographic characteristics (gender and ethnicity) and psychological symptomology for adults living in a conflict zone in Israel

Effects of a saponin fraction extracted from Trigonella foenum-graecum L. and two commercially available saponins on sex ratio and gonad histology of Nile tilapa fry, Oreochromis niloticus (L.)

Over three million tonnes (t) of tilapia, mostly Nile tilapia (Oreochromis niloticus, L.), are produced annually making it the second most abundantly produced freshwater fish (FAO, 2010). Tilapia are mouthbreeders that often produce stunted populations under pond conditions; one means of prevention is to produce all-male fish with the additional advantage that males usually grow faster than females. All-male populations can be achieved by supplementing feed with androgens such as 17-α-Methyltestosterone (MT) during days 10–25 post-hatch (Pandian and Sheela, 1995). However, MT is considered to be carcinogenic (Velazquez and Alter, 2004), and Hulak et al. (2008) also showed that effluents of systems in which carp were fed diets containing MT caused masculinization of female fish. Furthermore, in aquaculture the application of hormones to fish destined for human consumption is prohibited in the European Union under directive 96/22/EC, article 5, which also prohibits import of animal products produced with hormones. Kwon et al. (2000) showed that Fadrozole, a non-steroidal compound, caused masculinization in tilapia by inhibiting aromatase, which is the enzyme responsible for the conversion of endogenous androgens to estrogens. Steinbronn et al. (2004) were able to show that a dose of 2000 ppm Quillaja saponins (Sigma S-2149) inhibited reproduction of tilapia after dietary application for 32 days to first-feeding fry, suggesting saponins as a possible alternative to MT. These secondary plant compounds consist of either a steroid or triterpenoid basic structure (aglycone or sapogenin) plus one or more sugar side chains (Francis et al., 2002a). In a previous experiment a saponin fraction from the soapbark tree (Quillaja saponaria M.) inhibited aromatase in vitro (Golan et al., 2008). The fenugreek plant (Trigonella foenum-graecum L), widely cultivated in the Middle East and Asia, also has a high saponin content. The experiment was therefore conducted to test whether saponin fractions from Q. saponaria and from T. foenum-graecum were able to influence the sex ratio and gonad histology of Nile tilapia

A rhythm analysis method for exercise electrocardiograms

Ankara : The Department of Electrical and Electronics Engineering and Institute of Engineering and Sciences of Bilkent University, 1996.Thesis (Master's) -- Bilkent University, 1996.Includes bibliographical references leaves 44-46Exercise electrocardiography (the exercise ECG test or the stress EGG test) is one of the most popular and the most important non-invasive diagnostic tests in the field of cardiovascular disease. Arrhythmia analysis is an important part of the exercise ECG. A new approach to arrhythmia analysis is proposed in this thesis. 12 lead ECG signal is first reduced into three orthogonal channels which contain all the power of ECG. The orthogonalization process, an online Singular Value Decomposition (SVD) algorithm, maintains that these channels are free from both baseline wander and EMG noise. The third output channel has very low power with respect to first two. Making use of the orthogonality of these new channels. Total Power Signal (TPS) is calculated by summing the squares of orthogonalized channels. Employing the first two channels in TPS yields 92-99% of ECG power contained in all channels. Any arrhythmic behaviour during exercise test effects the TPS. In order to obtain the fiducial points of QRS complex first derivative of TPS is calculated. The method is compared with an algorithm proposed previously. The method and the algorithm are tested on 22 complete stress ECG test each with a duration between 9.5 to 26.5 minutes.Çağlar, B KeremM.S

The unfolded protein response affects readthrough of premature termination codons

One-third of monogenic inherited diseases result from premature termination codons (PTCs). Readthrough of in-frame PTCs enables synthesis of full-length functional proteins. However, extended variability in the response to readthrough treatment is found among patients, which correlates with the level of nonsense transcripts. Here, we aimed to reveal cellular pathways affecting this inter-patient variability. We show that activation of the unfolded protein response (UPR) governs the response to readthrough treatment by regulating the levels of transcripts carrying PTCs. Quantitative proteomic analyses showed substantial differences in UPR activation between patients carrying PTCs, correlating with their response. We further found a significant inverse correlation between the UPR and nonsense-mediated mRNA decay (NMD), suggesting a feedback loop between these homeostatic pathways. We uncovered and characterized the mechanism underlying this NMD-UPR feedback loop, which augments both UPR activation and NMD attenuation. Importantly, this feedback loop enhances the response to readthrough treatment, highlighting its clinical importance. Altogether, our study demonstrates the importance of the UPR and its regulatory network for genetic diseases caused by PTCs and for cell homeostasis under normal conditions

New approaches to genetic therapies for cystic fibrosis

Gene therapy offers great promise for cystic fibrosis which has never been quite fulfilled due to the challenges of delivering sufficient amounts of the CFTR gene and expression persistence for a sufficient period of time in the lungs to have any effect. Initial trials explored both viral and non-viral vectors but failed to achieve a significant breakthrough. However, in recent years, new opportunities have emerged that exploit our increased knowledge and understanding of the biology of CF and the airway epithelium. New technologies include new viral and non-viral vector approaches to delivery, but also alternative nucleic acid technologies including oligonucleotides and siRNA approaches for gene silencing and gene splicing, described in this review, as presented at the 2019 annual European CF Society Basic Science meeting (Dubrovnik, Croatia). We also briefly discuss other emerging technologies including mRNA and CRISPR gene editing that are advancing rapidly. The future prospects for genetic therapies for CF are now diverse and more promising probably than any time since the discovery of the CF gene

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

<div><p>Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in <i>Cftr^F508del</i> homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the <i>F508del-CFTR</i> mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from <i>F508del</i> homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both <i>in vivo</i>, in mice, and <i>in vitro</i>, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 <i>F508del-CFTR</i> homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells <i>in vivo</i>, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of <i>TNF/TNF-alpha (tumor necrosis factor)</i> and <i>CXCL8</i> (<i>chemokine [C-X-C motif] ligand 8</i>) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the <i>F508del-CFTR</i> mutation.</p></div