Pyrazinamide Effects on Cartilage Type II Collagen Amino Acid Composition

Introduction. Current therapeutic regimens with first-line antitubercular agents are associated to a high rate of adverse effects which could cause pronounced changes in collagen's contents and structure. Investigation of these changes is very important for optimization of antitubercular therapy and minimization of treatment-caused harm. The aim of present paper was to investigate potential effect of pyrazinamide on male rats' cartilage type II collagen amino acid composition. Materials and Methods. Wistar albino male rats (160–200 g b.w.) were divided into three groups: I—received pyrazinamide per os at a dose of 1000 mg/kg b.w./day; II—at a dose of 2000 mg/kg b.w./day, in both groups it was given for 60 days; III—control. After 60 days of the experiment, rats of the experimental (groups I and II) and control groups were sacrificed and the amino acids contents of male rat cartilage type II collagens were determined using amino acid analyzer. Results and Discussion. The study of pyrazinamide effects (administered in different doses) on rat cartilage type II collagen amino acid contents demonstrated presence of dose-dependent pyrazinamide-mediated quantitative and qualitative changes in these rat extracellular matrix proteins in comparison with control

Poremećaji reprodukcijske funkcije u mužjaka štakora uzrokovani unosom tekućine bogate fruktozom od 23 dana starosti do puberteta

There is compelling evidence that a hypercaloric, high-fructose diet can cause metabolic syndrome (MetS) and a whole range of other metabolic changes. In the context of androgen deficiency, MetS in boys merits special attention, but the effects of fructose-rich diet in youth on future male reproductive function are still poorly evidenced. The aim of this study was to address this issue and analyse the effects of high-fructose intake starting from weaning to puberty (postnatal day 23 up to 83) on the reproductive function of male rats. For this purpose juvenile male Wistar rats were divided in two groups: control and the group receiving 10 % fructose solution instead of drinking water. Reproductive function was evaluated in terms of fertility, sperm count, testes/epididymis morphology, and serum sex hormones. The fructose-treated group showed a decrease in testosterone and twofold increase in luteinising and follicle-stimulating hormone levels in the serum. This was accompanied with lower testis/epididymis weights, sperm count, and changed testis/epididymis morphology. Their fertility remained unchanged, but the fertility of females mating with these males diminished. In addition, pre-implantation and post-implantation embryonic death rate rose in these females. Our results have confirmed that high fructose consumption from early age until puberty can impair the reproductive function of male rats, and call for further animal and epidemiological investigation.Postoje snažni dokazi da hiperkalorična prehrana bogata fruktozom može uzrokovati metabolički sindrom (MetS) i cijeli niz drugih promjena u metabolizmu. U smislu androgene deficijencije, MetS u dječaka izaziva posebnu pažnju, ali nema mnogo spoznaja o učincima prehrane bogate fruktozom u ranoj mladosti na buduću reprodukcijsku funkciju u muškaraca. Stoga je cilj ovoga istraživanja bio analizirati učinke unosa tekućine bogate fruktozom u mladih mužjaka štakora od trenutka kad su prestali sisati (23 dana starosti) do puberteta (83 dana starosti) na njihovu reprodukcijsku funkciju. U tu su svrhu muški Wistar štakori podijeljeni u dvije skupine: kontrolnu i onu koja je primala 10 %-tnu otopinu fruktoze umjesto vode za piće. Parametri procjene reprodukcijske funkcije obuhvatili su plodnost, broj spermija, morfologiju testisa (sjemenika) i epididimisa (pasjemenika) te razine spolnih hormona u serumu. U skupini koja je primala fruktozu zamijećeno je smanjenje razine testosterona i dvostruko povećanje razina luteinizirajućega i folikulostimulirajućega hormona u serumu u odnosu na kontrolnu skupinu. Te su promjene popraćene padom težine testisa i epididimisa, broja spermija te promjenama u morfologiji testisa i epididimisa. Plodnost im se nije promijenila, ali je zato plodnost ženki koje su se parile s mužjacima izloženima fruktozi bila smanjena. Osim toga, u tih se ženki povećala smrtnost embrija prije i nakon implantacije u odnosu na ženke koje su se parile s kontrolnim mužjacima. Naši rezultati potvrđuju pretpostavku da konzumacija hrane i pića bogatih fruktozom od rane dobi do puberteta može oštetiti reprodukcijsku funkciju u štakora. Stoga je potrebno provesti daljnja istraživanja u životinja te epidemiološka istraživanja u ljudi

Ekspresija CYP2E1 u testisima štakora i alkoholom prouzrokovane promjene indeksa spermatogeneze i kolagena tipa I

This study is a complex investigation of alcohol-mediated changes in CYP2E1 mRNA and protein expression in the testes, as well as spermatogenesis indices and type I collagen amino acid contents, in male rats. Wistar albino male rats were divided into two groups: I – control (intact animals), II – experimental (chronic alcoholism, exposure to a 15 % ethanol aqueous solution during 150 days). The destructive changes in the spermatogenic epithelium were accompanied by a decrease in sperm number and motility time. CYP2E1 mRNA and protein expression were elevated in the testes 3 and 1.4 times, respectively. Also, significantly lower contents of lysine, glutamic acid, serine, proline, alanine, valine, and phenylalanine residues accompanied by an increase of hydroxyproline, glycine, and threonine residue contents were detected in the skin type I collagen of the experimental group. Chronic ethanol consumption caused testicular failure along with an overexpression of CYP2E1 mRNA and protein in the testes as well as quantitative changes in type I collagen amino acid contents. The profound alcohol-mediated changes in collagen type I amino acid contents may have affected the spermatogenic epithelium state. The modulation of testicular cytochrome P450 2E1 mRNA and protein expression could change the functioning of this isozyme in target organs and take part in the mechanism of ethanol gonadotoxicity.Ovo istraživanje proučava alkoholom uzrokovane promjene u ekspresiji CYP2E1 mRNA i bjelančevina iz testisa, indeksu spermatogeneze i aminokiselinskom sastavu kolagena tipa I u muških štakora. Albino štakori tipa Wistar podijeljeni su u dvije skupine: I – kontrolna, II – eksperimentalna (kronični alkoholizam, izloženi 150 dana 15-postotnoj vodenoj otopini etanola). Destruktivne promjene u spermatogenetskom epitelu popraćene su smanjenjem broja i pokretljivosti spermija. Ekspresija mRNA gena CYP2E1 i bjelančevina bila je povišena u testisima 3, odnosno 1,4 puta. Također, u kolagenu tipa I ustanovljene su značajno manje količine lizina, glutaminske kiseline, serina, prolina, alanina, valina i fenilalanina, te veće količine ostataka hidroksiprolina, glicina i treonina. Kronična konzumacija etanola uzrokovala je otkazivanje testisa uz izraženu ekspresiju mRNA CYP2E1 i bjelančevina u testisima, te kvantitativne promjene u aminokiselinama kolagena tipa I. Izražene alkoholom prouzrokovane promjene mogle su utjecati na spermatogenetski epitel. Modulacija ekspresije mRNA testikularnog citokroma P450-2E1 i bjelančevina mogla bi promijeniti djelovanje ovoga izozima u ciljnim organima te sudjelovati u mehanizmu gonadotoksičnosti etanola

Canine leishmaniosis and its relationship to human visceral leishmaniasis in Eastern Uzbekistan

<p>Abstract</p> <p>Background</p> <p>The Namangan Region in the Pap District, located in Eastern Uzbekistan is the main focus of visceral leishmaniasis (VL) in Uzbekistan. In total, 28 cases of human VL were registered during 2006-2008 in this region. A study on the epidemiology of VL in this area was carried out in 2007-2008 in the villages of Chodak, Oltinkan, Gulistan and Chorkesar located at elevations of 900-1200 above sea level.</p> <p>Results</p> <p>A total of 162 dogs were tested for <it>Leishmania </it>infection. Blood was drawn for serology and PCR. When clinical signs of the disease were present, aspirates from lymph nodes and the spleen were taken. Forty-two dogs (25.9%) had clinical signs suggestive of VL and 51 (31.5%) were sero-positive. ITS-1 PCR was performed for 135 dogs using blood and tissue samples and 40 (29.6%) of them were PCR-positive. Leishmanial parasites were cultured from lymph node or spleen aspirates from 10 dogs.</p> <p>Eight <it>Leishmania </it>strains isolated from dogs were typed by multi-locus microsatellite typing (MLMT) and by multilocus enzyme electrophoretic analysis (MLEE), using a 15 enzyme system. These analyses revealed that the strains belong to the most common zymodeme of <it>L. infantum</it>, i.e., MON-1, and form a unique group when compared to MON-1 strains from other geographical regions.</p> <p>Conclusions</p> <p>The data obtained through this study confirm the existence of an active focus of VL in the Namangan region of Uzbekistan. The fact that <it>L. infantum </it>was the causative agent of canine infection with typical clinical signs, and also of human infection affecting only infants, suggests that a zoonotic form of VL similar in epidemiology to Mediterranean VL is present in Uzbekistan.</p

Strong reduction of the off-momentum halo in crystal assisted collimation of the SPS beam

A study of crystal assisted collimation has been continued at the CERN SPS for different energies of stored beams using 120 GeV/. c and 270 GeV/. c protons and Pb ions with 270 GeV/. c per charge. A bent silicon crystal used as a primary collimator deflected halo particles using channeling and directing them into the tungsten absorber. A strong correlation of the beam losses in the crystal and off-momentum halo intensity measured in the first high dispersion (HD) area downstream was observed. In channeling conditions, the beam loss rate induced by inelastic interactions of particles with nuclei is significantly reduced in comparison with the non-oriented crystal. A maximal reduction of beam losses in the crystal larger than 20 was observed with 270 GeV/. c protons. The off-momentum halo intensity measured in the HD area was also strongly reduced in channeling conditions. The reduction coefficient was larger than 7 for the case of Pb ions. A strong loss reduction was also detected in regions of the SPS ring far from the collimation area. It was shown by simulations that the miscut angle between the crystal surface and its crystallographic planes doubled the beam losses in the aligned crystal.peer-reviewe

Comparative results on collimation of the SPS beam of protons and Pb ions with bent crystals

New experiments on crystal assisted collimation have been carried out at the CERN SPS with stored beams of 120 GeV/. c protons and Pb ions. Bent silicon crystals of 2 mm long with about 170 μrad bend angle and a small residual torsion were used as primary collimators. In channeling conditions, the beam loss rate induced by inelastic interactions of particles with the crystal nuclei is minimal. The loss reduction was about 6 for protons and about 3 for Pb ions. Lower reduction value for Pb ions can be explained by their considerably larger ionization losses in the crystal. In one of the crystals, the measured fraction of the Pb ion beam halo deflected in channeling conditions was 74%, a value very close to that for protons. The intensity of the off-momentum halo leaking out from the collimation station was measured in the first high dispersion area downstream. The particle population in the shadow of the secondary collimator-absorber was considerably smaller in channeling conditions than for amorphous orientations of the crystal. The corresponding reduction was in the range of 2-5 for both protons and Pb ions.peer-reviewe

Observation of parametric X-rays produced by 400 GeV/c protons in bent crystals

Spectral maxima of parametric X-ray radiation (PXR) produced by 400 GeV/c protons in bent silicon crystals aligned with the beam have been observed in an experiment at the H8 external beam of the CERN SPS. The total yield of PXR photons was about 10-6 per proton. Agreement between calculations and the experimental data shows that the PXR kinematic theory is valid for bent crystals with sufficiently small curvature as used in the experiment. The intensity of PXR emitted from halo protons in a bent crystal used as a primary collimator in a circular accelerator may be considered as a possible tool to control its crystal structure, which is slowly damaged because of irradiation. The intensity distribution of PXR peaks depends on the crystal thickness intersected by the beam, which changes for different orientations of a crystal collimator. This dependence may be used to control crystal collimator alignment by analyzing PXR spectra produced by halo protons.peer-reviewe

The efficacy of the combination of eribulin and trastuzumab in advanced HER2-positive breast cancer: the results of Russian observational study

The article presents the experience of 19 Russian medical institutions on the use of eribulin in combination with trastuzumab in various treatment lines of metastatic HER2+ breast cancer in routine clinical practice. Aim. The main objective of this retrospective observational study was to evaluate the efficacy and tolerability of eribulin and trastuzumab combo in HER2+ breast cancer patients pretreated with anthracyclines and taxanes. The analysis included 60 patients who received at least 2 cycles of eribulin in combination with trastuzumab. 2 patients (3.3%) received treatment as the 1st line, as the 2nd 14 (23.3%), as the 3rd 16 (26.7%), and as the 4th and more 28 (46.7%). Materials and methods. Complete response was achieved in 2 (3.3%) patients, partial response in 9 (15%), stable disease in 33 (55%), stabilization for more than 6 months in 11 (18.3%), disease progression was detected in 16 (26.7%) patients. The objective response rate was 18.3% in the whole group, the clinical benefit rate 36.7%. Results. The objective response rate in the group of the luminal subtype (ER/PR+HER2+) was 26.9%, in HER2-overexpressed subtype (ER-PR-HER2+) 8.8% and 64.7%, respectively, disease progression was recorded 2.3 times more often 35.3% versus 15.5% in the luminal subtype group. The median progression-free survival in patients with HER2+ breast cancer was 4.95 months (95% confidence interval CI 3.048.29 months), in luminal subtype 6.38 months (95% CI 3.338.54 months), in non-luminal 4.44 months (95% CI 2.47.96 months); p=0.306. The treatment was well tolerated, the spectrum of adverse events corresponded to the eribulin toxicity profile. Conclusions. The uniqueness of this study lies in the fact that on a large clinical material from the standpoint of real clinical practice, a very promising treatment regimen that is not used routinely in a number of countries has been studied, its effectiveness and satisfactory tolerance have been confirmed

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe