Evaluation of uroprotective efficacy of amifostine against cyclophosphamide induced hemorrhagic cystitis

The role of amifostine in the prevention of cyclophosphamide-induced hemorrhagic cystitis (HC) was evaluated in the rat model. Urinary bladders from control rats that received no drugs (group I) were compared with those from rats receiving cyclophosphamide alone at a dose of 150 mg/kg (group II), and two other groups receiving amifostine at 100 mg/kg (group III) and 200 mg/kg (group IV), 15 min prior to cyclophosphamide. Bladders were assessed macroscopically and histologically at 24 h and after 7 days. All the animals that received cyclophosphamide alone developed severe HC. On the basis of the scores of macroscopic and histologic changes, animals that received amifostine showed excellent uroprotection. Only 2/6 rats in group III and 1/6 rats in group IV developed mild HC at 24 h. None of the rats in either of these groups showed any evidence of HC at 7 days. It is concluded that amifostine protects the urothelium against cyclophosphamide-induced HC

Spatiotemporal modeling of air pollutant concentrations in Germany using machine learning

Machine learning (ML) models are becoming a meaningful tool for modeling air pollutant concentrations. ML models are capable of learning and modeling complex nonlinear interactions between variables, and they require less computational effort than chemical transport models (CTMs). In this study, we used gradient-boosted tree (GBT) and multi-layer perceptron (MLP; neural network) algorithms to model near-surface nitrogen dioxide (NO2) and ozone (O3) concentrations over Germany at 0.1∘ spatial resolution and daily intervals. We trained the ML models using TROPOspheric Monitoring Instrument (TROPOMI) satellite column measurements combined with information on emission sources, air pollutant precursors, and meteorology as feature variables. We found that the trained GBT model for NO2 and O3 explained a major portion of the observed concentrations (R2=0.68–0.88 and RMSE=4.77–8.67 µg m−3; R2=0.74–0.92 and RMSE=8.53–13.2 µg m−3, respectively). The trained MLP model performed worse than the trained GBT model for both NO2 and O3 (R2=0.46–0.82 and R2=0.42–0.9, respectively). Our NO2 GBT model outperforms the CAMS model, a data-assimilated CTM but slightly underperforms for O3. However, our NO2 and O3 ML models require less computational effort than CTM. Therefore, we can analyze people's exposure to near-surface NO2 and O3 with significantly less effort. During the study period (30 April 2018 and 1 July 2021), it was found that around 36 % of people lived in locations where the World Health Organization (WHO) NO2 limit was exceeded for more than 25 % of the days during the study period, while 90 % of the population resided in areas where the WHO O3 limit was surpassed for over 25 % of the study days. Although metropolitan areas had high NO2 concentrations, rural areas, particularly in southern Germany, had high O3 concentrations. Furthermore, our ML models can be used to evaluate the effectiveness of mitigation policies. Near-surface NO2 and O3 concentration changes during the 2020 COVID-19 lockdown period over Germany were indeed reproduced by the GBT model, with meteorology-normalized near-surface NO2 having significantly decreased (by 23±5.3 %) and meteorology-normalized near-surface O3 having slightly increased (by 1±4.6 %) over 10 major German metropolitan areas when compared to 2019. Finally, our O3 GBT model is highly transferable to neighboring countries and locations where no measurements are available (R2=0.87–0.94), whereas our NO2 GBT model is moderately transferable (R2=0.32–0.64).</p

Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic

Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD) injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n = 109) or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n = 108), intramuscularly. Pain intensity (PI) was self-evaluated by patients on visual analogue scale (VAS) at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID) at 8 hours, and sum of analogue of pain intensity differences (SAPID). Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P < 0.0001), PID at 8 hours (P = 0.002), and SAPID0–8 hours (P = 0.004). The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic

Effect of hydrogen on ground state structures of small silicon clusters

We present results for ground state structures of small Si$_{n}$H (2 \leq \emph{n} \leq 10) clusters using the Car-Parrinello molecular dynamics. In particular, we focus on how the addition of a hydrogen atom affects the ground state geometry, total energy and the first excited electronic level gap of an Si$_{n}$ cluster. We discuss the nature of bonding of hydrogen in these clusters. We find that hydrogen bonds with two silicon atoms only in Si$_{2}$H, Si$_{3}$H and Si$_{5}$H clusters, while in other clusters (i.e. Si$_{4}$H, Si$_{6}$H, Si$_{7}$H, Si$_{8}$H, Si$_{9}$H and Si$_{10}$H) hydrogen is bonded to only one silicon atom. Also in the case of a compact and closed silicon cluster hydrogen bonds to the cluster from outside. We find that the first excited electronic level gap of Si$_{n}$ and Si$_{n}$H fluctuates as a function of size and this may provide a first principles basis for the short-range potential fluctuations in hydrogenated amorphous silicon. Our results show that the addition of a single hydrogen can cause large changes in the electronic structure of a silicon cluster, though the geometry is not much affected. Our calculation of the lowest energy fragmentation products of Si$_{n}$H clusters shows that hydrogen is easily removed from Si$_{n}$H clusters.Comment: one latex file named script.tex including table and figure caption. Six postscript figure files. figure_1a.ps and figure_1b.ps are files representing Fig. 1 in the main tex

Preliminarno ispitivanje antimikotskog i citotoksičnog djelovanja derivata cikloalkil[b]tiofena PLS-DA analizom

A series of 2-[(arylidene)amino]-cycloalkyl[b]thiophene-3-carbonitriles (2a-x) was synthesized by incorporation of substituted aromatic aldehydes in Gewald adducts (1a-c). The title compounds were screened for their antifungal activity against Candida krusei and Criptococcusneoformans and for their antiproliferative activity against a panel of 3 human cancer cell lines (HT29, NCI H-292 and HEP). Forantiproliferative activity, the partial least squares (PLS) methodology was applied. Some of the prepared compounds exhibited promising antifungal and proliferative properties. The most active compounds for antifungal activity were cyclohexyl[b]thiophene derivatives, and forantiproliferative activity cycloheptyl[b]thiophene derivatives, especially 2-[(1H-indol-2-yl-methylidene)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbonitrile (2r), which inhibited more than 97 % growth of the three cell lines. The PLS discriminant analysis (PLS-DA)applied generated good exploratory and predictive results and showed that the descriptors having shape characteristics were strongly correlated with the biological data.Koristeći supstituirane aromatske aldehide u Gewaldovim aduktima 1a-c sintetizirani su derivati 2-[(ariliden)amino]-cikloalkil[b]tiofen-3-karbonitrila (2a-x). Ispitano je antimikotsko djelovanje tih spojeva na gljivice Candida krusei i Criptococcus neoformans te antiproliferativno djelovanje na tri humane tumorske stanične linije (HT29, NCI H-292 i HEP). Za antiproliferativno djelovanje primijenjena je metoda parcijalnih najmanjih kvadrata (PLS) koristeći softverski program Pentacle. Neki od ispitanih spojeva pokazuju obećavajuće antimikotsko i antiproliferativno djelovanje. Najjače antimikotsko djelovanje imaju cikloheksil[b]tiofen derivati, a najjače antiproliferativno djelovanje cikloheptil[b]tiofen derivati, posebice 2-[(1H-indol-2-il-metiliden)amino]-5,6,7,8-tetrahidro-4H-ciklohepta[b]tiofen-3-karbonitril (2r), koji inhibira više od 97 % rast svih triju ispitivanih staničnih linija. Primijenjena PLS diskriminirajuća analiza dala je dobre istraživačke i prognostičke rezultate i pokazala da deskriptori dobro koreliraju s biološkim rezultatima

Cecal obstruction due to primary intestinal tuberculosis: a case series

<p>Abstract</p> <p>Introduction</p> <p>Primary intestinal tuberculosis is a rare variant of tuberculosis. The preferred treatment is usually pharmaceutical, but surgery may be required for complicated cases.</p> <p>Case presentation</p> <p>We report two cases of primary intestinal tuberculosis where the initial diagnosis was wrong, with colonic cancer suggested in the first case and a Crohn's disease complication in the second. Both of our patients were Caucasians of Greek nationality. In the first case (a 60-year-old man), a right hemicolectomy was performed. In the second case (a 26-year-old man), excision was impossible due to the local conditions and peritoneal implantations. Histopathology revealed an inflammatory mass of tuberculous origin in the first case. In the second, cell culture and polymerase chain reaction tests revealed <it>Mycobacterium tuberculosis</it>. Both patients were given anti-tuberculosis therapy and their post-operative follow-up was uneventful.</p> <p>Conclusions</p> <p>Gastrointestinal tuberculosis still appears sporadically and should be considered in the differential diagnosis along with other conditions of the bowel. The use of immunosuppressants and new pharmaceutical agents can change the prevalence of tuberculosis.</p

Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation

The mutant proinsulin syndrome is a monogenic cause of diabetes mellitus due to toxic misfolding of insulin's biosynthetic precursor. Also designated mutant INS-gene induced diabetes of the young (MIDY), this syndrome defines molecular determinants of foldability in the endoplasmic reticulum (ER) of β-cells. Here, we describe a peptide model of a key proinsulin folding intermediate and variants containing representative clinical mutations; the latter perturb invariant core sites in native proinsulin (LeuB15→Pro, LeuA16→Pro, and PheB24→Ser). The studies exploited a 49-residue single-chain synthetic precursor (designated DesDi), previously shown to optimize in vitro efficiency of disulfide pairing. Parent and variant peptides contain a single disulfide bridge (cystine B19-A20) to provide a model of proinsulin's first oxidative folding intermediate. The peptides were characterized by circular dichroism and redox stability in relation to effects of the mutations on (a) in vitro foldability of the corresponding insulin analogs and (b) ER stress induced in cell culture on expression of the corresponding variant proinsulins. Striking correlations were observed between peptide biophysical properties, degree of ER stress and age of diabetes onset (neonatal or adolescent). Our findings suggest that age of onset reflects the extent to which nascent structure is destabilized in proinsulin's putative folding nucleus. We envisage that such peptide models will enable high-resolution structural studies of key folding determinants and in turn permit molecular dissection of phenotype-genotype relationships in this monogenic diabetes syndrome. Our companion study (next article in this issue) employs two-dimensional heteronuclear NMR spectroscopy to define site-specific perturbations in the variant peptides

Strongly Coupled Magnetic and Electronic Transitions in Multivalent Strontium Cobaltites

The topotactic phase transition in SrCoOx (x = 2.5-3.0) makes it possible to reversibly transit between the two distinct phases, i.e. the brownmillerite SrCoO2.5 that is a room-temperature antiferromagnetic insulator (AFM-I) and the perovskite SrCoO3 that is a ferromagnetic metal (FM-M), owing to their multiple valence states. For the intermediate x values, the two distinct phases are expected to strongly compete with each other. With oxidation of SrCoO2.5, however, it has been conjectured that the magnetic transition is decoupled to the electronic phase transition, i.e., the AFM-to-FM transition occurs before the insulator-to-metal transition (IMT), which is still controversial. Here, we bridge the gap between the two-phase transitions by density-functional theory calculations combined with optical spectroscopy. We confirm that the IMT actually occurs concomitantly with the FM transition near the oxygen content x = 2.75. Strong charge-spin coupling drives the concurrent IMT and AFM-to-FM transition, which fosters the near room-T magnetic transition characteristic. Ultimately, our study demonstrates that SrCoOx is an intriguingly rare candidate for inducing coupled magnetic and electronic transition via fast and reversible redox reactions