Effects of Acute Administration of D,L-Homocysteine Thiolactone on the Antioxidative Status of Rat Intestine and Liver

Oxidative stress appears to play a role in the pathogenesis of several inflammatory gastrointestinal diseases. Increased homocysteine levels may play a role in the pathogenesis of Chrons disease and ulcerative colitis. The aim of this study was to examine the influence of homocysteine on the antioxidant status of rat intestine and liver. The levels of thiobarbituric acid reactive substances (TBARS), activity of catalase (CAT) and total antioxidant status (TAS) were investigated in the isolated gut and liver of young male rats in the control group (8 rats) and after 3-hour incubation in high doses of D, L-homocysteine thionolactone (Hcy) (10 mu mol/L) (8 rats). Samples of duodenum, ileum, colon and liver were homogenized in sodium phosphate buffer (1: 10). Homogenates were centrifuged at 10000 for 10 min at 4 degrees C and the supernatant was taken for biochemical assays. Our results showed that high D, L-homocysteine thionolactone concentration reduced enzymatic catalase activity in homogenates of the isolated segments of duodenum (27.04%) p LT 0.01; ileum (37.27%), colon (34.17%) and liver (67.46%) p LT 0.001. Exposition to high D, L-homocysteine thiolactone concentration significantly increased TBARS levels in the duodenum (106.05%), ileum (47.24%), colon (112.75%) and liver (32.07%) (p LT 0.01). Homocysteine also modified the total antioxidant status of homogenates from the duodenum, ileum, colon and liver, increasing by 20.68% (duodenum), 24.74% (ileum), 14.88% (colon) and 19.35% (liver) (p LT 0.001). Homocysteine induced a consistent oxidative stress in rats intestine and liver (reduced activity of catalase and increased level of TBARS), but the elevated activity of TAS in our experiments could be explained as an adaptive response to the generated free radicals which indicates the failure of the total antioxidant defense mechanism to protect the tissues from damage caused by homocysteine

Differences in antimicrobial consumption, prescribing and isolation rate of multidrug resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii on surgical and medical wards.

In order to provide guidance data for clinically rational use of an antibiotics consuption, prescribing and prevalence of multidrug resistant (MDR) Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii were monitored on the surgical (S) and medical (M) wards of the University Hospital Center "Dr. Dragisa Misovic-Dedinje" (Belgrade, Serbia), in the study period from 2012 to 2015. Appropriateness of antimicrobial use was evaluated using the Global-Prevalence Survey method designed by the University of Antwerp. The percentages of MDR pathogens relative to the total number of isolates of K. pneumoniae and P. aeruginosa were higher on the S (86.2% and 49.1%) than on the M (63.2% and 36.9%) wards. The percentage of MDR A. baumannii was not different between S (93.7%) and M (79.5%) wards. An overall antibiotics consumption (defined daily doses/100 bed-days) during study was 369.7 and 261.5 on the S and M wards, respectively. A total of 225 prescriptions of antimicrobials were evaluated in138 adults admitted to wards on the day of the survey. The percentage of antimicrobials prescribed for prophylaxis on the M and S wards were 0% and 25%, respectively. Therapies were more frequently empiric (S, 86.8% and M, 80%). The percentages of medical errors on the S and M wards were 74.6% and 27.3%, respectively. The quality indicators for antibiotic prescribing on the S and M wards were as follows: the incorrect choice of antimicrobials (35.6% vs. 20.0%), inappropriate dose interval (70.6% vs. 16.9%) or duration of therapy (72.5% vs. 23.1%), a non-documented stop/review data (73.6% vs. 16.9%) and divergence from guidelines (71.9% vs. 23.1%). Treatment based on biomarkers was more common on the M wards as compared to the S wards. The increasing prevalence of MDR pathogens, a very high consumption and incorrect prescribing of antimicrobials need special attention, particularly on the S wards

The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

Hyperhomocysteinemia (HHC), both basal and after methionine load, may occur due to genetic disorders or deficiencies of nutrients that affect the remethylation or trans-sulphuration pathways during methionine metabolism. HHC is involved in the pathogenesis of many illnesses as a result of its prooxidative effect and its impairment of antioxidative protection. The aim was to examine the effects of subchronic methionine overload on the body weight and standard biochemical parameters in rat serum and to examine whether simultaneous subchronic intraperotoneal administration of methionine alone or together with L-cysteine or N-acetyl-cysteine resulted in a change in the body weight and biochemical parameters in the rat serum. The research was conducted during a three-week period (male Wistar albino rats, n=36, body weight of approximately 160 g, age of 15-20 days), and the animals were divided into a control group and three experimental groups of 8-10 animals each: a) control group (0.9% sodium chloride 0.1-0.2 ml/day); b) methionine (0.8 mmol/kg/bw/day) (MET group); c) methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (L-cys+MET group); and d) methionine (0.8 mmol/kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (NAC+MET group). In addition to the body weight monitoring, the levels of total homocysteine and the standard biochemical parameters in blood samples (plasma or serum) were determined. The results indicated that monitoring the homocysteine levels and standard biochemical parameters in blood could be used for analysis and could provide an excellent guideline for distinguishing between toxic and non-toxic doses of methionine intake, which may be meaningful for clinical applications

Annual distribution of isolation rates and patients on surgical and medical wards.

<p>Annual distribution of isolation rates and patients on surgical and medical wards.</p

Types and frequency of appearance of bacterial strains from 2012 to 2015.

<p>Types and frequency of appearance of bacterial strains from 2012 to 2015.</p

Association between antimicrobial consumption and isolation rate of multi drugs resistant <i>K</i>. <i>pneumoniae</i>, <i>P</i>. <i>aeruginosa</i> and <i>A</i>. <i>baumannii</i> at surgical (A) and medical (B) wards.

<p>Association between antimicrobial consumption and isolation rate of multi drugs resistant <i>K</i>. <i>pneumoniae</i>, <i>P</i>. <i>aeruginosa</i> and <i>A</i>. <i>baumannii</i> at surgical (A) and medical (B) wards.</p

Resistance rate (%) of <i>Klebsiella pneumoniae</i>, <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i> strains isolated from 2012–2015.

<p>Resistance rate (%) of <i>Klebsiella pneumoniae</i>, <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i> strains isolated from 2012–2015.</p

Main indications for antimicrobial therapy from 2012 to 2015.

<p>Main indications for antimicrobial therapy from 2012 to 2015.</p

Trends of antibiotic consumption by individual drugs on surgical (A) and medical (B) wards from 2012 to 2015.

<p>A. *There was a statistically significant decrease in the use of amoxicillin/clavulanate (b = -2.881; p = 0.014). B. *There was a statistically significant decrease in the use of ceftriaxone (b = -2.925; p = 0.047). **There was a statistically significant increase in the use of levofloxacin (b = 2.745; p = 0.014). ***There was a statistically significant increase in the use of metronidazole (b = 1.385; p = 0.029).</p

Quality of antimicrobial prescribing obtained by Global-Point Prevalence Survey method.

<p>Quality of antimicrobial prescribing obtained by Global-Point Prevalence Survey method.</p