The cholecysto-sphincter of Oddi reflex

Multiple factors including hormonal and neural influences as well as intravascular volume, body temperature, and pharmacologic agents have been shown to influence sphincter of Oddi function. Recent studies have also suggested that mechanical or electrical stimulation of the gallbladder and the degree of gallbladder filling may affect the frequency and amplitude of sphincter of Oddi phasic contractions. However, the effect of gallbladder filling on sphincter of Oddi phasic wave direction has not previously been studied. In acute terminal experiments, eight adult male prairie dogs underwent cannulation of the gallbladder with a pressure-monitored perfusion catheter. The common bile duct was cannulated proximally with a drainage catheter and distally with a triple-lumen, side-hole, closed-tipped catheter. The distal port of this catheter was positioned in the sphincter of Oddi (SO) while the proximal port was in the distal common bile duct (CBD). Distal CBD and SO phasic wave activity was recorded first with the gallbladder perfused with lactated Ringer's solution at 0.1 ml/min (mean intragallbladder pressure 8.1 ± 0.3 mm Hg) and then with the gallbladder (GB) empty. Sphincter of Oddi phasic wave frequency was 6.7 ± 0.9/min with the GB full and 5.4 ± 0.6/min with the GB empty (P < 0.02). Phasic wave amplitude was also greater with the GB full versus empty in both the distal CBD (6.4 ± 0.6 vs 4.3 ± 0.5 mm Hg, P < 0.05) and the SO (9.5 ± 1.5 vs 6.4 ± 0.8, P = 0.075). Baseline pressures and the direction of phasic waves were unaffected by the degree of gallbladder filling. It is concluded that the degree of gallbladder filling reflexly influences sphincter of Oddi phasic wave activity and should be considered in future studies of the choledochoduodenal junction.     

A Synthetic Analog of Resveratrol Inhibits the Proangiogenic Response of Liver Sinusoidal Cells during Hepatic Metastasis

We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.     

Maternal Apical Periodontitis Increases Insulin Resistance and Modulates the Antioxidant Defense System in the Gastrocnemius Muscle of Adult Offspring

IntroductionMaternal apical periodontitis (AP) is associated with insulin resistance (IR) in adult offspring. Oxidative stress has been linked to IR. This study investigated insulin sensitivity (IS) and oxidative stress in the gastrocnemius muscle (GM) of adult offspring of rats with AP.MethodsFifteen female Wistar rats were distributed into a control group, a group with 1 tooth with AP, and a group with 4 teeth with AP. Thirty days after AP induction, female rats were mated with healthy male rats. When male offspring reached 75 days of age, glycemia, insulinemia, and IS were determined. In the GM, the oxidative damage products (thiobarbituric acid reactive substances and carbonyl protein) and activities of enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (glutathione and total antioxidant capacity) antioxidants were quantified. Analysis of variance was performed followed by the Tukey post hoc test (P < .05).ResultsMaternal AP was associated with decreased IS and changes in antioxidant activities (reduced superoxide dismutase and increased catalase, glutathione peroxidase, and glutathione) and decreased thiobarbituric acid reactive substance concentration in the GM of their adult offspring. However, maternal AP does not appear to affect glycemia, carbonyl protein concentration, and the nonenzymatic total antioxidant capacity in the GM of this offspring.ConclusionsMaternal AP modulates the antioxidant defense system in the GM of their adult offspring, attenuating lipid peroxidation in this tissue. This reflects part of an adaptive response of the offspring to the stimulation of the maternal chronic oral inflammatory process in which the organism acts by decreasing oxidative tissue damage in the postnatal stage. The present study improves knowledge about the impact of maternal oral inflammation on healthy offspring.     

Four limonoids from the seeds extract of Sandoricum koetjape

Journal of Natural Medicines - Three andirobin- and one trijugin-class limonoids, named koetjapins A-D (1–4), have been isolated from the seed extracts of Sandoricum koetjape. The structures...     

Automatic Methods for Carotid Contrast-Enhanced Ultrasound Imaging Quantification of Adventitial Vasa Vasorum

Adventitial vasa vasorum are physiologic microvessels that nourish artery walls. In the presence of cardiovascular risk factors, these microvessels proliferate abnormally. Studies have reported that they are the first stage of atheromatous disease. Contrast-enhanced ultrasound (CEUS) of the carotid allows direct, quantitative and non-invasive visualization of the adventitial vasa vasorum. Hence, the development of computer-assisted methods that speed image analysis and eliminate user subjectivity is important. We developed methods for automatic analyses and quantification of vasa vasorum neovascularization in CEUS and tested these methods in a cohort of 186 individuals, 63 of whom were healthy volunteers. We implemented alternative automatic strategies for using the images to stratify patients according to their risk group and compare the strategies with respect to diagnostic performance. An automatic single-parameter strategy performs less effectively than the corresponding Arcidiacono method based on manual interpretation of the images (68 < area under the receiver operating characteristic curve [AUROC] for the manual Arcidiacono method < 82; 60 < AUROC for the automatic single-parameter strategy < 63). However, by use of additional image parameters, an automatic multiparameter strategy has significantly improved performance with respect to the manual Arcidiacono method (78 < AUROC < 90). The automatic multiparameter strategy is a valuable alternative to the manual Arcidiacono method, improving both diagnostic speed and diagnostic accuracy.     

Changes of liver fat content and transaminases in obese children after 12-mo nutritional intervention

AIM: To assess a relationship between longitudinal changes in liver fat content and biochemical parameters in obese children after 1-year nutritional intervention.METHODS: Forty-six obese children, 21 males and 25 females, aged 6-14 years, underwent metabolic measurements, liver ultrasonography (US) and chemical-shift magnetic resonance imaging (MRI) examinations at baseline and after 1-year nutritional intervention. A child was defined obese if her/his body mass index (BMI) was above the age- and sex-adjusted BMI Cole’s curve passing through the cut-off of 30 kg/m² at 18 years. BMI Z scores were calculated and adjusted for age and gender by using the Cole’s LMS-method and Italian reference data. Biochemistry included serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Abdominal US and chemical-shift MRI were performed according to a randomized sequence. The same radiologist performed US by a GE Logiq 9 (General Electric Healthcare Medical Systems, Milwaukee, WI, United States) using a 3.5-MHz convex array transducer. Liver echogenicity was evaluated independently on videotape by 3 radiologists unaware of the child and MRI outcomes, and a consensus was established. Another experienced radiologist, unaware of the child and US data, performed the abdominal chemical-shift MRI with a 1-t system NT-Intera (Philips Medical Systems, Best, The Netherlands) and a phased-array coil. Liver fat fraction (FF) on MRI was judged elevated when greater than 9%. A FF > 18% was considered expressing more severe cases of fatty liver according to Fishbein. A nutritional-behavioral intervention was recommended to promote a normocaloric balanced diet and active lifestyle based on the Italian guidelines for treatment of childhood obesity.RESULTS: Compared to baseline, at the end of intervention children showed lower intakes of energy (mean ± SD: 2549 ± 1238 Kcal vs 1770 ± 622 Kcal, P < 0.0001), total fat (90 ± 47 g vs 52 ± 23 g, P < 0.0001), carbohydrates (356 ± 174 g vs 241 ± 111 g, P = 0.001), and protein (99 ± 48 g vs 75 ± 23 g, P = 0.006) intakes. Prevalence of FF ≥ 9% declined from 34.8% to 8.7% (P < 0.01), with a mean reduction of 7.8% (95%CI: 5.0-10.6). At baseline, FF was associated with liver biochemical parameters (maximum P < 0.001). At the end of the intervention association was found with AST (P = 0.017). Change of FF was associated with change in AST (P = 0.027) and ALT (P = 0.024). Rate of increased liver echogenicity declined from 45.6% to 21.7% (P < 0.0001). Liver echogenicity was associated with ALT at baseline only (P < 0.001). An age- and sex- adjusted multiple regression analysis showed that FF change was independently associated with change in serum AST (adjusted regression coefficient 0.348, P = 0.048).CONCLUSION: The results suggest that in obese children longitudinal changes in liver fat content based on MRI may be associated with change in serum transaminases suggesting novelty in monitoring nonalcoholic fatty liver disease.     

The hemolysin-producer coelomocytes in Holothuria polii

Using sodium metrizoate discontinuous gradients, two hemolysin-producer amebocyte populations have been separated from total circulating Holothuria polii coelomocytes. The amebocytes of population 1 are responsible for the production of the calcium-dependent and temperature-labile hemolysin, whereas those of population 2 produce the calcium-independent and temperature-stable one. The intracytoplasmic hemolysins were evidenced also by immunofluorescence. Petaloid and filipodial amebocytes were the only positive cell types.