Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments

Background In hepatobiliary imaging, systems detect the total amount of agents originating from extracellular space, bile canaliculi, and hepatocytes. They add in situ concentration of each compartment corrected by its respective volume ratio to provide liver concentrations. In vivo contribution of each compartment to liver concentration is inaccessible. Our aim was to quantify the compartmental distribution of two hepatobiliary agents in an ex vivo model and determine how their liver extraction ratios and cholestasis (livers lacking canalicular transporters) might modify it. Methods We perfused labelled gadobenate dimeglumine (Bopta, 200 μM, 7% liver extraction ratio) and mebrofenin (Meb, 64 μM, 94% liver extraction ratio) in normal (n = 18) and cholestatic (n = 6) rat livers. We quantified liver concentrations with a gamma counter placed over livers. Concentrations in hepatocytes and bile canaliculi were calculated. Mann-Whitney and Kruskal-Wallis tests were used. Results Hepatocyte concentrations were 2,043 ± 333 μM (Meb) versus 360 ± 69 μM (Bopta, p < 0.001). Meb extracellular concentrations did not contribute to liver concentrations (1.3 ± 0.3%). The contribution of Bopta extracellular concentration was 12.4 ± 1.9% (p < 0.001 versus Meb). Contribution of canaliculi was similar for both agents (16%). Cholestatic livers had no Bopta in canaliculi but their hepatocyte concentrations increased in comparison to normal livers. Conclusion Hepatocyte concentrations are correlated to liver extraction ratios of hepatobiliary agents. When Bopta is not present in canaliculi of cholestatic livers, hepatocyte concentrations increase in comparison to normal livers. This new understanding extends the interpretation of clinical liver images.

DETERMINATION OF THE OPTIMUM CONDITIONS FOR UREASE INHIBITTION EXTRACTED FROM SOME LOCAL PLANTS

In the current study, four types of plants commonly used namely Soybean, chickpea, bean, pea were obtained and screened for urease activity, among this plants, chickpea was chosen with maximum enzymatic activity, and it had the highest productivity of urease enzyme (1243 U/mg protein). Also sodium acetate buffer (0.2 M, pH 5.0) was chosen as a best extraction buffer with specific activity 1460 U/mg protein. The optimum extraction ratio represented by 1:8 (w:v) after 15 min, it was given 1988 U/mg protein. As well as four types of plants include garlic, red onion, green onion and cabbage were used to select the optimum plant material that inhibited urease enzyme. Cabbage was chosen, it had the highest inhibition activity of the enzyme (41%). Also tris buffer (0.2 M, pH 9) was selected as a best extraction buffer of plants inhibitor with inhibition activity 80%. The optimum extraction ratio represented by 1:8 (w:v) after 60 min, it was given 86% enzyme inhibition activity.

Oral health indicators and sociodemographic factors in Brazil from 2008 to 2015

OBJECTIVE: To evaluate the annual variation of oral health and primary care coverage, the tooth extraction ratio, and the average of supervised toothbrushing in Brazilian municipalities according to social development and population size. METHODS: Public secondary data were analyzed. The outcomes were health service indicators (oral health coverage, primary health care coverage, tooth extraction ratio, and average of supervised tooth brushing) estimated for all Brazilian municipalities annually from 2008 to 2015. Mixed-effect multilevel regression models with random intercept and slopes were fitted with a cross-interaction term to estimate the annual percent variation according to the Municipal Human Development Index (MHDI) and population size. RESULTS: Municipalities with low MHDI presented an annual increase in oral health and primary care coverage of 2.65% and 2.23%, respectively, which was significantly higher than municipalities with medium and high MHDI. Oral health and primary care coverage were 69.26% and 35.00% lower among municipalities with a large population. Municipalities with medium and high MHDI showed an annual decrease in tooth extractions of 5.15% and 5.02%, respectively. An annual decrease was observed in the average of supervised toothbrushing of 9.81% and 4.57% in municipalities with low and medium MHDI, respectively. The tooth extraction ratio was higher among larger municipalities; the relation is inverse for supervised toothbrushing. CONCLUSIONS: The access to primary care and oral health services increased in Brazil, while a decrease occurred in mutilating treatment and provision of preventive actions, with disparities among municipalities with different MHDI levels over time.

MO821OXYGEN EXTRACTION RATIO AND MORTALITY RISK IN HAEMODIALYSIS PATIENT: A MULTICENTRE STUDY

Background and Aims Patients on haemodialysis (HD) suffer a very high rate of cardiovascular mortality with some evidence suggesting a possible association with decreasing blood oxygen saturation (SO2) during sessions. The ratio between arterial SO2 (SaO2) and central venous SO2 (ScvO2) or Oxygen Extraction Ratio (OER), which represents an estimate of the amount of oxygen claimed by peripheral tissues and of the haemodialysis related hypoxic stress, might represent a new prognostic factor. Method We evaluate the relationship between OER values and mortality risks in HD patients in a prospective multicentre observational study. We enrolled chronic HD patients with permanent central venous catheter (CVC) and no fistula, in whom ScvO2 measurement is at hand and SaO2 is available with a peripheral oxymeter. OER ([(SaO2−ScvO2)/SaO2]×100) was measured before and after HD at enrolment (HD OER sessions) in each patients, and a one-year follow-up was planned to record the number of deaths. Results In 101 patients (age 71.5 ± 14 years on dialysis for 47 ± 38 months), during 9 ± 6 months of follow up, we recorded 35 deaths. Patients were then divided into two groups, above or below the median value of pre-HD OER, which was 30%. In these groups, the average incidence of deaths was 12% (24 deaths) and 5,5% (11 deaths) respectively (p&lt;0.05), with significantly different survival curves (Kaplan-Meier log rank test = 0.04, fig). No difference in mortality was evident if we divided patients according to the median intradialytic change in OER value. Conclusion Patients with pre-HD OER &gt; 30% have a higher mortality risk, most probably secondary to reduced capability to respond to HD related oxygen requirements. OER is novel biomarker to identify patients at greatest clinical risk.