Irina M. Jaba

In vitro and in vivo behavior of ketoprofen intercalated into layered double hydroxides.

Ketoprofen (Ket) was intercalated into layered double hydroxides (ZnAlLDH and MgAlLDH) using the ionic exchange method. The drug intercalation was confirmed by X-ray diffraction (XRD) and FTIR spectroscopy. Ket release from the inorganic matrix was studied at pH 7.4 in continuous regime with a flow rate of 0.5 and respectively 1.0xa0ml/min. The kinetical data were interpreted using the Ritger and Peppas model. The data prove that the release kinetics and mechanism depend on the eluent flow rate. Quantification of gastric tolerance shows that the ulcerogenic effect of the intercalated drug is lower than the one of the raw Ket. The antinociceptive effect of both formulations was studied by the hot-plate method performed on mice. The MgAlLDH_Ket formulation shows a tendency towards a stronger antinociceptive effect than its ZnAlLDH_Ket counterpart during the 210xa0min recorded period.

Is MARS system enough for A.phalloides-induced liver failure treatment?

Patients with Amanita phalloides-induced liver failure (LF) have a high mortality, despite significant advances in intensive care managemet. Our study evaluated the effect of Molecular Absorbents Recirculating System (MARS) comparative with optimal intensive care (OIC) in adults with this condition, in the absence of liver transplantation (LT). Six consecutive patients (women, range 16—61 years) affected by A.phalloides-induced LF were treated with OIC (3 patients) and MARS (3 patients). Laboratory parameters and hepeatic encephalopaty were evaluated 15 min before and 24 hours following each MARS treatment. Three 6-hour sessions per patient were performed in MARS group, with a statistically significant decrease in ammonia (p value 0.011), alaninaminotransferase (ALT) and prothrombin time (PT) (p value 0.004). Two patients had a significant rebound in bilirubin (+116%; p value 0. 04) 24 hours following MARS. Mortality in MARS group was 66.7%. Survival rate in OIC was 0%. Negative prognostic markers: lack of PT and hepatic encephalopaty improvement, rebound in bilirubin, and delay of MARS therapy initiation. No significant adverse reactions occurred during MARS. MARS is an effective depurative therapy in adults with A.phalloides-induced LF, but alone is not enough. Survival is predicted by the results of the initial MARS, amount of mushroom consumed, and time from toxin exposure.

Epidemiology of acute drug poisoning in a tertiary center from Iasi County, Romania

The aim of this retrospective epidemiological study was to investigate the demographical, etiological and clinical characteristics of acute drug poisonings in Iasi County, Romania. All patients were referred and admitted in the Toxicology Clinic of “Sf. Ioan” Emergency Clinic Hospital Iasi, Romania. Between 2003 and 2009, 811 cases of acute drug poisonings were recorded, counting for 28.43% from the total number of poisonings. The majority of these poisonings resulted in mild (51.94%) and medium (28.35%) clinical forms, while 19.71% were coma situations. In all, 63.51% of patients originated from urban areas, 39.94% were unemployed and the patients were predominantly women (66.46%). A high percentage (97.27%) were suicide attempts, using only one type of drug (65.88%) and the 21–30 years group (29.8%) records the highest incidence, for both women and men. The most frequently involved drugs were benzodiazepines 13.69%, anticonvulsive drugs 8.63%, barbiturates 8.51% and cardiovascular drugs 5.92%. Drugs combinations were recorded in 32.92% of cases and 1.2% were combinations between drugs and other substances. Mortality was the outcome in 0.3% of the total registered number of acute drug poisonings. This study underlines that in order to provide a proper management of these situations, a Regional Poison Information Center is absolutely necessary.

Cardiac Troponin T and NT-proBNP as Biomarkers of Early Myocardial Damage in Amitriptyline-Induced Cardiovascular Toxicity in Rats:

The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex (P < .0001) and the QT interval (P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.

Variation in the analgesic activity of opioid peptide fragments in correlation with the amino acidic sequence

Short fragments of typical or atypical opioid peptides, lacking the whole four amino acid sequence of the enkephalin motif, can preserve a significant percentage of the analgesic activity of the original peptides. This paper investigates the importance of the amino-acidic sequence of minimum structure typical opioid peptides for the analgesic activity. Different groups of rats were treated with 1) Gly-Tyr, 0.5 mg/rat i.t., 2) Tyr-Gly, 0.5 mg/rat i.t., 3) Tyr-Gly-Gly, 0.5 mg/rat i.t., 4) Gly-Gly-Phe-Leu, 0.5 mg/rat i.t., 5) Leu-enkephalin, 0.5 mg/rat i.t.. The analgesic effect of the tested substances was appreciated through the nociceptive threshold for thermal (plantar test) and mechanical nociception (algesimetric test). Fragments of typical opioid peptides elicited antinociceptive activity only when a tyrosine residue was present at the N-terminal end of the amino-acidic sequence. The presence of Nterminal tyrosine provides affinity for the opioid receptors and significant analgesic activity. The intensity of the antinociceptive effect was directly proportional with the length of the amino-acidic sequence. The inhibition of the analgesic effect by previous administration of naloxone proves that this effect is mediated through the opioid system.

Profile of adult acute cholinesterase inhibitors substances poisoning – a 30 years analysis

Abstract Objectives: The objective of this study was to assess the pattern and outcome of acute cholinesterase inhibitors substances (CIS) poisoning cases, in a cohort from a regional tertiary care hospital. Methods: cases admitted in the Toxicology Clinic of “Sf. Spiridon” Emergency Clinic Hospital Iasi, Romania between 1983 and 2013 were studied. Results: a total number of 606 patients were included. The reason for exposures was intentional in 70% of cases and the commonest route of poisoning was oral in 92.2%. The highest percent of cases was females (56.4), the age group 20-29 (25.4%) and the majority (66.7%) coming from rural areas, 28.2% being agricultural workers. 36.6% of cases were severe clinical forms. Overall mortality rates were 3.8%, more than half of the death patients (65.2%) had concomitant alcohol intake. It was a significant statistical association between decrease level of serum cholinesterase on admittance and severe forms (p 0.000) and between survival and deaths groups (p 0.000). The pattern of poisoning described by our retrospective study suggests that CIS poisoning are mainly preventable. The main effective goals for prevention are restriction in free accessibility to toxic pesticides, together with sustained efforts in education concerning the life-threatening danger of pesticide poisoning.

Acute cardiac dyspnea in the emergency department: diagnostic value of N-terminal prohormone of brain natriuretic peptide and galectin-3

Objective This study was performed to determine whether a dual-biomarker approach using N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and galectin-3 optimizes the diagnosis and risk stratification of acute cardiac dyspnea. Atypical clinical manifestations and overlapping pathologies require objective and effective diagnostic methods to avoid treatment delays. Methods This prospective observational study included 208 patients who presented to the emergency department for acute dyspnea. NT-proBNP and galectin-3 were measured upon admission. The patients were divided into two groups according to the etiology of their clinical manifestations: cardiac and non-cardiac dyspnea. The patients’ New York Heart Association functional class, left ventricular ejection fraction, and discharge status were assessed. Results Diagnostic criteria for acute heart failure were fulfilled in 61.1% of the patients. NT-proBNP and galectin-3 were strongly and significantly correlated. Receiver operating characteristic analysis revealed similar areas under the curve for both markers in the entire group of patients as well as in the high-risk subsets of patients. Conclusions The diagnostic performance of NT-proBNP and galectin-3 is comparable for both the total population and high-risk subsets. Galectin-3 adds diagnostic value to the conventional NT-proBNP in patients with acute cardiac dyspnea, and its utility is of major interest in uncertain clinical situations.

Beyond the Arteries in Peripheral Artery Disease

Abstract Objectives. This study aimed to examine peripheral artery disease severity impact on psychological profile of arteriopathy patients. Material and methods. The prospective study included consecutive PAD patients admitted to the 2nd Department of Internal Medicine and the Department of Cardiology of the Emergency Clinical Hospital “Sf. Spiridon” Iasi, between January and September, 2017. Rezults. The group included 139 PAD patients, 80.6% male and 19.4% female, with an average age of 63.23±9.44 years. PAD stages have a very strong association with level of quality of life (p<0.0001). All Leriche-Fontaine classification categories were significantly associated with the depressive symptoms (p<0.0001). The stress level was moderate in stages IIA, IIB and III and extremely severe in the terminal stage. The prevalence of anxiety was lowest in incipient PADstages with the highest value in stage III. Conclusions. The fragment of the PhD study presented the psychological profile in the PAD staging and advocates a personalized, wide-ranging approach to the arteriopathy patient including pain and depressive-anxiety management, with amajor impact on the quality of life at terminal stages.