ANESTHETIC MANAGEMENT FOR A PATIENT WITH ACUTE INTERMITTENT PORPHYRIA

Acute intermittent porphyria is a rare metabolic disorder resulting from a partial deficiency of porphobilinogen deaminase, enzyme in the heme biosynthetic pathway. Its inheritance is autosomal dominant. A deficiency of porphobilinogen deaminase is not sufficient by its self to produce acute intermittent porphyria, and other activating factors must also be present. These include some drugs, hormones, infection, injury and alcohol. Besides others, anesthetics have been implicated in the triggering of a number of severe porphyric reactions. Although there is no clinical evidence, the fear of hypothesized porphyrinogenicity of repetitive anesthetics exposures still remains. Despite these doubts, we report here the case of uneventful repeated exposure to anesthetics in a patient suffering from acute intermittent porphyria, within a fifteen- month period. On both occasions, the patient was safely exposed to certain anesthetics included: propofol, sevoflurane, rocuronium, midazolam and fentanyl

Modulating Horizontal Gene Transfer through Bistability in the Dynamics of Bacterial Restriction-Modification Systems

Restriction-modification (R-M) systems consist of genes encoding restriction enzyme and methyltransferase, often co-expressed with a specialized regulator (C protein). These systems tightly regulate their function through complex cooperative positive and negative feedback loops. R-M systems defend bacterial cells against invasion by foreign DNA, such as plasmids and bacteriophages, consequently modulating horizontal gene transfer, including transmitting pathogenic genes like antibiotic resistance determinants or virulence factors. Recent experiments have directly confirmed that the R-to-M ratio significantly impacts bacteriophage infection efficiency, rendering a subset of cells more susceptible to horizontal gene transfer. To understand the regulatory mechanisms of R-M systems, we develop a mathematical model tightly constrained by biophysical measurements of system interaction parameters. Despite the technical complexity arising from C protein forming dimer and tetramer complexes, we analytically derive a system stability diagram that can be easily modified for various R-M system architectures. A single free parameter determines the bistability of the system, which we infer from experimental measurements across three different architectures. Surprisingly, while one class exhibits monostability, the other two demonstrate bistability. Our model successfully explains the experimental data and reveals that modulation of the barrier to horizontal gene transfer can occur through distinct mechanisms. Bistability leads to long-lasting states susceptible to acquiring pathogenic genes, whereas stochastic fluctuations only transiently lower the transfer barrier. The precise implications of these differences for bacterial pathogenicity and evolution require further investigation. However, we propose that R-M systems capable of bistable gene expression may give rise to genetically distinct bacterial populations with potentially diverse phenotypes concerning pathogenicity and antibiotic resistance.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202

NEFROPATIJA POVEZANA S VARFARINOM – PRIKAZ BOLESNIKA NA TEMELJU BIOPSIJE BUBREGA I PREGLED LITERATURE

Warfarin-related nephropathy (WRN) is a recently recognized condition in patients with chronic kidney disease (CKD). WRN is clinically detected as an episode of unexplained acute kidney injury (AKI). It is defined as a serum creatinine (sCR) increase >0.3 mg/dL (26.5 μmol/L) within one week of an international normalized ratio (INR) measurement >3.0 in a patient treated with warfarin without clinical evidence of hemorrhage. Therefore, warfarin therapy can result in AKI by causing glomerular hemorrhage and renal tubular obstruction by red blood cell casts. WRN appears to accelerate the rate of CKD progression and increase the risk of death in susceptible patients. We report on renal biopsy in a patient on warfarin therapy with unexplained AKI and hematuria associated with increased INR. We would like to stress the necessity of an interdisciplinary approach to patients on warfarin therapy.Nefropatija povezana s varfarinom (WRN) je odnedavno prepoznato stanje u bolesnika s kroničnom bolešću bubrega (KBB). WRN je klinički prepoznata kao epizoda neobjašnjivog akutnog oštećenja bubrega (AOB). Definira se kao povećanje kreatinina u serumu (sCR) >0,3 mg/dL (26,5 micromol/L) unutar tjedna INR mjerenja >3,0 u bolesnika liječenog varfarinom bez klinički utvrđenog krvarenja. Zbog toga terapija varfarinom može dovesti do AOB uzrokujući glomerularno krvarenje i opstrukciju bubrežnih tubula odljevnim cilindrima eritrocita. Čini se da WRN ubrzava napredovanje KBB i u osjetljivih bolesnika povećava rizik od smrtnog ishoda.Izvješćujemo o biopsiji bubrega u bolesnika na terapiji varfarinom s neobjašnjivim AOB i hematurijom povezanom s povećanim INR. Namjera nam je naglasiti potrebu interdisciplinarnog pristupa bolesnicima na terapiji varfarinom

ESTIMATION OF RISK FACTORS OF EARLY POSTOPERATIVE MORTALITY IN ELDERLY PATIENTS WHO ARE SUBJECTED TO GASTRIC SURGICAL PROCEDURES

The use of screening programms in elderly population (age ≥65 years) comprises an increasing proportion of patients undergoing emergency general surgery (EGS) procedures nowadays. The aim was to determine the intra-hospital mortality rate in elderly patients undergoing gastric surgical procedures. 108 elderly patients (≥65 years old) were examined, divided into two groups: deceased and surviving surgical patients, treated for diseases (benign and malignant) of the stomach. The patients were divided into four age groups and five ASA groups, taking into account the presence of chronic diseases, the values of some laboratory parameters, administered transfusion and the occurrence of surgical complications during hospitalization. The mortality rate among elderly patients was 28.7%. The significant risk factors for mortality were: emergency surgery (p < 0.001), bleeding gastric ulcer operations (p = 0.042), lung (p = 0.003), kidney (p < 0.001), heart (p = 0.025) diseases, ASA score of 4 or higher (p < 0.001), serum levels (higher after two times measurement) of creatinine, haemoglobin, CRP, PCT and glycemia (p < 0.001). In order to improve medical treatment, the determination of independent validated risk indicators for mortality in elderly patients might lead to developing a dedicated scoring system

Microbial diversity and isolation of multiple metal-tolerant bacteria from surface and underground pits within the copper mining and smelting complex Bor

The bacterial diversity of the surface and deep sediment of the Copper Mining and Smelting Complex Bor, Serbia, was investigated using culture-dependent and culture-independent approaches. Sequencing analysis of 16S rDNA libraries revealed greater bacterial diversity in the surface sediment of the mining complex (MS) in comparison to deeper mine sediment (MU). While in the MS sample members of seven different phylogenetic groups were detected, in the MU sample library representatives of only three different groups were detected. The use of a culture-dependent approach revealed the presence of only three bacterial groups in both samples: Actinobacteria, Firmicutes and Proteobacteria, while six isolates exhibiting the highest metal tolerance were members of Arthrobacter and Staphylococcus genera. The most promising isolate, MSI08, was able to grow in the presence of high concentrations of Cd2+ (535 μM), Ni2+(17 mM) and Cr6+ (38.5 mM) and as such this indigenous strain has potential in the bioremediation of the contaminated surrounds of the city of Bor

Hemijske karakteristike visoko-krečnjačkih zemljišta koje određuju raspodelu fosfora

Phosphorus fractions from three highly calcareous soils (average, 24.9 +/- 4.8 %CO32-) from sampling sites with a Mediterranean climate were isolated by sequential extraction. In order to provide a more reliable basis for the definition of the obtained P-fractions, principal component analysis was applied and from the chemical characteristics of the 14 investigated soils, those characteristics which define at he content and association features of the P-fractions were assessed. The soils are characterized by a relatively high pH (8.0-8.2) and by significantly differing contents of organic mater, acid-soluble Mg and total P. These differences affected the various association features of the P-fraction with the soil constituents. The NH4F-P fraction (isolated with 0.5 M NH4F, pH 8.2) is defined by the contents of the main metals of the oxide-hydroxide-clay associations (Al, Fe, Mn) or by the the redox potential (Eh) of Mn. The accumulation of NaOH-phosphorus (extractable with 0.1 M NaOH) depended on the constituents of the oxide hydroxide-clay association, the humic substances and Eh-related factors. In those soils in which NaOH-P is defined by the oxide-hydroxide-clay association, the participation of Fe as a bridge-forming metal is proposed. The main part of total P, i.e., Delta P = TP - (NH4F-P + NaOH-P) is defined by the status of Mn- and Fe-humic complexes or by the concentration of hydroxyl-ions.Iz tri visoko-krečnjačka zemljišta (prosečni sadržaj CO 3 2- 24.9 ± 4.8%, pH 8.0 - 8.2), sa lokacija sa sredozemnom klimom, izolovane su frakcije fosfora sekvencijalnom ekstrakcijom. U cilju obezbeđivanja pouzdanije osnove za definisanje dobijenih frakcijafosfora (P-frakcija), primenjena je analiza principalne komponente (PC-analiza). Među 14 hemijskih karakteristika zemljišta, izdvojene su one koje definišu sadržaj pojedinih P-frakcija i prirodu njihove asocijacije sa sastojcima zemljišta. Frakcija NH 4-P (izolovana sa 0,5M NH 4F, pH = 8,2) definisana je sadržajem glavnih metala oksidne-hidroksidne-glinene asocijacije (Al, Fe, Mn) ili Eh-statusom izraženim sadržajem Mn. Akumulacija NaOH-P (ekstrahovanog sa 0,1 M NaOH) zavisila je od sastojaka oksidne-hidroksidne-glinene asocijacije, od huminskih supstanci i od faktora koji stoje u vezi sa Eh. U onim zemljištima u kojima je NaOH-P definisana sastojcima oksidne-hidroksidne-glinene asocijacije, pretpostavljeno je vezivanje fosfora preko Fe-mostova. Glavna količina fosfora ∆P = TP - (NH 4F-P + NaOH-P), u pojedinim zemljištima definisana je ili statusom Mn- i Fe-huminskih kompleksa, ili pH-vrednošću

GENERATION AND MONITORING OF METHANE AT A MUNICIPAL WASTE LANDFILL

Abstract. This paper describes oxidation reactions of methane, as the prevalently emitted landfill gas, as well as reactions of oxidative pyrolysis with all the important factors influencing the final amount of methane emission: air temperature, landfill body temperature, pressure, humidity, and soil structure. Based on theoretical background and measures of methane emissions at 24 measuring points at the “Meteris” landfill in the town of Vranje, we analyzed the data on methane exceeding the maximum allowable values in ambient air and the possibility of a fire due to methane’s flammability limit being reached. The paper also provides a description of the “Meteris” landfill general features. Key words: waste, landfill, landfill gas, methan

Distinct effects of virgin coconut oil supplementation on the glucose and lipid homeostasis in non-diabetic and alloxan-induced diabetic rats

Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgincoconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to controlglycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementationwith coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity ofsteatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on hearthistology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither innon-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementationwith coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development ofsevere insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contra-indicated in diabetic condition

Insights into conformational and cristal structure features of selected cyclohexane-5-spirohydantoin derivatives

Derivat cikloheksan-5-spirohidantoina (Slika 1) je sintetisan, određena je njegova kristalnastruktura i urađena kvantno-hemijska analiza. Kristalno pakovanje grade mrežesupramolekulskih R64(32) prstenova postavljenih međusobno paralelno, pri čemu seformiraju linearni kanali. Određene su vrednosti energije intermolekulskih interakcija zarazličite dimerne motive dobijene iz kristalne strukture. Uzimajući u razmatranjeprethodno strukturno okarakterisane srodne spirohidantoine [1], dobijena je serijajedinjenja koja je omogućila procenu uticaja supstituenata na njihovu molekulsku ikristalnu strukturu.A spirohydantoin derivative (Figure 1) was synthesized and its crystal structure wasdetermined by single crystal X-ray diffraction and analysed by DFT calculations. Thecrystal packing is made of supramolecular nets of R64(32) rings linked together to formstacks that enclose linear channels. The intermolecular interaction energies are quantifiedfor various dimeric motifs. By including the previously reported structurally-relatedspirohydantoins [1], we created a set of compounds that enabled us to evaluate substituenteffects on both molecular and crystal structures

Role of structural motifs in formation of the supramolecular architecture of 3-(4-tert-butylbenzoyl)-1,3-diazaspiro[4.5]Decane-2,4-dione

Proučavano jedinjenje (slika 1) sintetisano je polazeći od cikloheksanona Bučerer- Bergsovom reakcijom i naknadnim acilovanjem dobijenog spirohidantoina. Izgradnja kristalne strukture ovog jedinjenja proučavana je sa aspekta doprinosa jednostavnih dimernih motiva koji se uspostavljaju preko različitih intermolekulskih interakcija.Intermolekulske interakcije dodatno su proučavane pomoću Hiršfeldovih površina i 2D grafičkih prikaza otisaka interakcija. Kristalna struktura, naime, zadržava motiv koji se često sreće kod derivata hidantoina, u kome su dva inverzano orijentisana molekula povezana parom N–H···O vodoničnih veza. Ovaj motiv formira dva tipa dvostrukih lanaca, koji dalje grade sloj (slika 2). Osim toga, slabe C–H⋯O interakcije zajedno sa disperzionim interakcijama (π-π i hidrofobne interakcije) identifikovane su u ovoj kristalnoj strukturi. Kristalografski podaci: C19H24N2O3, Mr = 328,4, trikliničan sistem, prostorna grupa P–1, a = 6,2810(2), b = 12,0586(4), c = 12,1852(5) Å,α = 77,624(3), β = 81,039(3), γ = 79,111(3) °, V = 878.81(6) Å3, Z = 2, F(000) = 352, ρx = 1,380 g cm–3,µ(MoKα) = 0,084 mm–1. Utačnjavanje sa F2 (220 parametara) dalo je R1 = 0,0520, wR2 = 0,1199, S = 1,033 za sve podatke i R1 = 0,0443 za 3232 uočenih refleksija sa I ≥ 2σ(I).The title compound (Figure 1) was prepared from cyclohexanone in the Bucherer-Bergs reaction, followed by acylation of the obtained spirohydantoin. Formation of the crystal structure of this compound was analysed in terms of a number of simple dimeric motifs which are associated with different intermolecular interactions. The crystal structure retains the motif commonly found in hydantoin derivatives, where two molecules related by inversion are linked by a pair of N–H O hydrogen bonds. This motif is involved in two types of double chains, whichfurther form a layer (Figure 2). Intermolecular interactions were also investigated using Hirshfeld surface analysis and 2D fingerprint analysis. Weak C–H⋯O interactions together with thedispersion interactions (π-π and hydrophobic) as the source of attraction are identified in this crystal structure.Crystal data: C19H24N2O3, Mr = 328.4, triclinic system, space group P–1, a = 6.2810(2), b = 12.0586(4), c = 12.1852(5) Å, a = 77.624(3), β = 81.039(3), γ = 79.111(3) °, V = 878.81(6) Å3, Z = 2, F(000) = 352,ρx = 1.380 g cm–3, µ(MoKa) == 0.084 mm–1. The refinement on F2 (220 parameters) yielded R1 = 0.0520, wR2 = 0.1199,S = 1.033 for all data, and R1 = 0.0443 for 3232 observed reflections with I ≥ 2σ(I)