Bile Pigments Research Articles

Heme-Derived Metabolic Signals Dictate Immune Responses.

Heme is one of the most abundant molecules in the body acting as the functional core of hemoglobin/myoglobin involved in the O2/CO2 carrying in the blood and tissues, redox enzymes and cytochromes in mitochondria. However, free heme is toxic and therefore its removal is a significant priority for the host. Heme is a well-established danger-associated molecular pattern (DAMP), which binds to toll-like receptor 4 (TLR4) to induce immune responses. Heme-derived metabolites including the bile pigments, biliverdin (BV) and bilirubin (BR), were first identified as toxic drivers of neonatal jaundice in 1800 but have only recently been appreciated as endogenous drivers of multiple signaling pathways involved in protection from oxidative stress and regulators of immune responses. The tissue concentration of heme, BV and BR is tightly controlled. Heme oxygenase-1 (HO-1, encoded by HMOX1) produces BV by heme degradation, while biliverdin reductase-A (BLVR-A) generates BR by the subsequent conversion of BV. BLVR-A is a fascinating protein that possesses a classical protein kinase domain, which is activated in response to BV binding to its enzymatic site and initiates the downstream mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. This links BLVR-A activity to cell growth and survival pathways. BLVR-A also contains a bZip DNA binding domain and a nuclear export sequence (NES) and acts as a transcription factor to regulate the expression of immune modulatory genes. Here we will discuss the role of heme-related immune response and the potential for targeting the heme system for therapies directed toward hepatitis and cancer.

БИОХИМИЧЕСКИЕ ПОКАЗАТЕЛИ КРОВИ БЕСПОРОДНЫХ КРЫС

The aim of the work was to determine some biochemical parameters, taking into account the sex of the outbred (conventional) rats in the norm, used at the experiment to determine the reference val-ues. The experiments were carried out on 41 rats of 5-6 months age old., weighing 200-250 g, divided into two groups - males (n = 16) and fe-males (n = 25). Blood serum was obtained accord-ing to the generally accepted method. Blood serum was obtained according to standard methods. Biochemical parameters were analyzed on an IDEXX CatalystOne automated analyzer. Protein and carbohy-drate metabolism were analyzed by the se-rum levels of total protein (TP), albumin (Alb), urea (Urea), creatinine (Creat), glu-cose (Glu), the enzyme spectrum - by alka-line phosphatase (ALP), alanine and aspar-tate aminotransferase (ALT and AST), min-eral metabolism - by calcium (Ca), phospho-rus (P), sodium (Na), potassium (K), chlo-rine (Cl), as well as bile pigment - by total bilirubin (T.bil). De Ritis coefficient (AST / ALT), globulin (Glob), albumin/globulin ratio (A / G) was revealed by the calculation method. The results were taken into account in two versions: 1 - according to all animals (16 males and 25 females); 2 - according to samples from the general population in three replicates. It was found that out of 17 biochemical parameters -15 are constant, due to the sex of the experimental animals. So, females showed higher indicators of protein and min-eral metabolism, glucose, ALT, alkaline phosphatase, while in males this was record-ed only in four cases - in the content of urea and AST and in the ratios A / G, AST / ALT. Data on the content of creatinine and total bilirubin in the blood serum of rats were variable in nature and were close in value. Thus, the results of the studies carried out can be used in the future, for biochemical diagnostics of systematic metaboli

Persistent Hyperbilirubinaemia with Absence of Urinary Bile Salts and Bile Pigments

Persistent Hyperbilirubinaemia with Absence of Urinary Bile Salts and Bile Pigments

Ultrafast spectroscopy of biliverdin dimethyl ester in solution: pathways of excited-state depopulation.

Biliverdin is a bile pigment that has a very low fluorescence quantum yield in solution, but serves as a chromophore in far-red fluorescent proteins being developed for bio-imaging. In this work, excited-state dynamics of biliverdin dimethyl ether (BVE) in solvents were investigated using femtosecond (fs) and picosecond (ps) time-resolved absorption and fluorescence spectroscopy. This study is the first fs timescale investigation of BVE in solvents, and therefore revealed numerous dynamics that were not resolved in previous, 200 ps time resolution measurements. Viscosity- and isotope-dependent experiments were performed to identify the contributions of isomerization and proton transfer to the excited-state dynamics. In aprotic solvents, a ∼2 ps non-radiative decay accounts for 95% of the excited-state population loss. In addition, a minor ∼30 ps emissive decay pathway is likely associated with an incomplete isomerization process around the C15[double bond, length as m-dash]C16 double bond that results in a flip of the D-ring. In protic solvents, the dynamics are more complex due to hydrogen bond interactions between solute and solvent. In this case, the ∼2 ps decay pathway is a minor channel (15%), whereas ∼70% of the excited-state population decays through an 800 fs emissive pathway. The ∼30 ps timescale associated with isomerization is also observed in protic solvents. The most significant difference in protic solvents is the presence of a >300 ps timescale in which BVE can decay through an emissive state, in parallel with excited-state proton transfer to the solvent. Interestingly, a small fraction of a luminous species, which we designate lumin-BVE (LBVE), is present in protic solvents.

Density functional theory studies on the excited-state properties of Bilirubin molecule

Bilirubin is the main pigment in human bile, which is closely related to human health. Bilirubin combining with fluorescent protein represents a new type of fluorescent chromophore and has important applications in the field of biological imaging and biosensor. Due to the lack of efficient and accurate electronic structure methods, the electronic structure and excited-state properties of bilirubin molecule are not characterized quantitatively and accurately. Firstly, the vertical absorption energy, oscillator strength and vertical emission energy of the lowest singlet excited state of bilirubin molecule are calculated by combining the implicit solvent model and the linear response time-dependent density functional theory (TDDFT) method. Compared to the experimental data and high-level RI-ADC(2) calculation, the prediction performance of a series of density functional methods is systematically investigated. The results show that the optimally-tuned range separated density functional method has the best overall performance and the minimum absolute and relative errors. This is obviously due to the fact that the suitable proportion of exact exchange included in density functionals can produce neither delocalized nor localized electronic structures. Based on the produced wavefunction by the optimally-tuned method, the excited-state characteristics of the S<sub>1</sub> state of bilirubin molecule indicate a hybrid local and charge transfer excitation, based on the quantitative characterization using hole-electron analysis and interfragment charge transfer method. This work can provide a theoretical basis for the study of excited-state dynamics and spectral properties of bilirubin molecules and the optimally tuned range-separated DFT method also provide a reliable and efficient theoretical tool to study the excited-state properties of other biomolecular systems in the future.

Septicaemia due to a Proteus infection in a Humboldt penguin (Spheniscus humboldti)

A 2-year-old male Humboldt penguin (Spheniscus humboldti) died after a very brief period of illness at a zoo aquarium; the penguin showed sudden depression, anorexia, dyspnoea, and had recurrent melena a day prior to death. The gross examination revealed an extensive bilious effusion in the abdominal cavity due to a gallbladder rupture. Moreover, abscess formation, purulent exudate, severe congestion, and haemorrhages were observed in the trachea and parenchymal organs such as the kidneys and the lungs. A histopathological examination revealed a fibrin deposition with a severe haemorrhage and secondary infiltration of chronic-active inflammatory cells in the parabronchi, atria, and air capillaries and blood vessels of the lungs as well as in most of the parenchymal organs. Moreover, Gram-negative bacilli were found in the lumen of the gastrointestinal tracts including the small and large intestines accompanied by severe epithelial necrosis and the capsule of the liver. Especially, bile pigments were microscopically observed in the whole liver, which indicated a gallbladder rupture. Samples collected from the trachea, lungs, and blood were cultured on a blood agar, and the pure colonies of Proteus genus were isolated. Proteus mirabilis, P. penneri, P. vulgaris, and P. cibarius were identified with polymerase chain reaction (PCR). As a result, the diagnosis was confirmed as Proteus septicaemia. To our knowledge, this is the first report of concomitant infection by different Proteus species that eventually resulted in septicaemia in a Humboldt penguin, and it will provide valuable information for zoo veterinarians for its diagnosis as well, since Humboldt penguins are the most widely found penguins in zoos and Proteus septicaemia in the penguins has, to the best of our knowledge, not been reported as yet.

A Simple and Cost Effective Turn off Fluorescence Sensor for Biliverdin and Bilirubin Based on L-Cysteine Modulated Copper Nanoclusters.

The present article reports the efficiency of L-cysteine modulated copper nanoclusters (L-cys-CuNCs) as a fluorescent probe for the selective determination of naturally occurring bile pigments biliverdin (BVD) and bilirubin (BLR). These pigments were found to quench the fluorescence of L-cys-CuNCs through static processes. Under optimized conditions, the proposed strategy permitted the quantification of BVD and BLR in the range 4.00 × 10-5 to 5.00 × 10-7M and 1.00×10-5 to 1.00×10-6 M respectively with limits of detection 2.33 × 10-7M and 2.29 × 10-7M. The practical utility of the developed sensor have been investigated in spiked blood and urine samples.

Overview of pigmented nephropathy

Abstract: Pigment nephropathy defined as an abrupt decrease in renal function due to the toxic effect of endogenous haem-containing pigment on the kidney like myoglobin which released from skeletal muscle in rhabdomyolysis and free hemoglobin in intravascular hemolysis and bile pigment in cholestasis. pigment nephropathy is one of the causes of acute kidney injury labile iron playing a central role in renal sideropathy. Inflammation is the most important mechanism of pigment induced acute renal injury. Sterile inflammation is mediated through the inflammasome. The most important one is nucleotide-binding domain-like receptor protein 3 (NLRP3) which involved in most inflammatory mediated renal diseases. Inhibiting the inflammasomes may significantly reduce damaging which occurs in the kidney. Prevention playing a vital step in the management of pigment nephropathy, clinical suspicion, and biochemical investigations is a challenge to identify the risk of the condition before progression to AKI. Intravenous fluid replacement to correct hypovolemia and guard against cast formation in the renal tubules preventing progression to acute renal failure.

1I. Vitamin D receptor-like receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Vitamin D (VDR), Pregnane X (PXR) and Constitutive Androstane (CAR) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [47]) are members of the NR1I family of nuclear receptors, which form heterodimers with members of the retinoid X receptor family. PXR and CAR are activated by a range of exogenous compounds, with no established endogenous physiological agonists, although high concentrations of bile acids and bile pigments activate PXR and CAR [47].

Bile duct involvement by hepatocellular carcinoma: A rare occurrence and poor prognostic indicator in bile duct brushing samples.

Hepatocellular carcinoma (HCC) rarely involves the biliary tree and may be inadvertently sampled on bile duct brushings (BDBs). The pathology archives of 5 institutions were searched for BDBs with HCC involvement. A total of 17 BDBs from 14 patients were obtained. There was a male:female ratio of 6:1; the median age of the patients was 59.5years (range, 22-80years). The median hepatic tumor size was 6.2cm (range, 2.2-13.0cm). HCC risk factors included viral hepatitis (5 patients), cirrhosis (5 patients), hemochromatosis (1 patient), and alcoholic steatohepatitis (1 patient). Jaundice with elevated bilirubin, liver enzymes, and α-fetoprotein was common. Endoscopic retrograde cholangiopancreatography demonstrated bile duct dilatation, polypoid intraductal masses (5 samples), clots/debris (2 samples), or strictures (4 samples). All BDBs had single and clustered large cells with naked atypical nuclei, granular cytoplasm, high nuclear/cytoplasmic ratios, and nuclei with prominent macronucleoli. Less common findings included clear/microvesicular cytoplasm (35%), papillae (29%), and anisonucleosis (35%). Classic HCC features (widened trabeculae [35%], endothelial wrapping [24%], multinucleation [24%], and cytoplasmic bile pigment [35%]) were uncommon. A total of 11 BDBs were diagnosed as malignant (10 with HCC and 1 with cholangiocarcinoma), 2 were diagnosed as atypical, and 1 BDB was diagnosed as negative; approximately two-thirds were found to have polysomy on fluorescence in situ hybridization. Approximately 71% of patients died of disease at a median of 3.5months. HCC may extend into the intrahepatic and/or extrahepatic biliary tree, causing masses and/or strictures that may be sampled on BDB. Although cytologically malignant, the classic features of HCC are uncommon, which can cause misdiagnosis. Cytopathologists should be mindful of this differential when evaluating BDBs, particularly when concomitant liver masses and/or HCC risk factors are present. Because of the associated high mortality and rapid rate of death, its presence should be conveyed clearly in pathology reports.

The complexity of porphyrin-like pigments in a marine annelid sheds new light on haem metabolism in aquatic invertebrates

True green pigments in the animal kingdom are scarce and are almost invariably porphyrinoids. Endogenous porphyrins resulting from the breakdown of haem are usually known as “bile pigments”. The pigmentation of intertidal Polychaeta has long gained attention due to its variety and vivid patterning that often seems incompatible with camouflage, as it occurs with Eulalia viridis, one of the few truly green Polychaeta. The present study combined UV and bright-field microscopy with HPLC to address the presence and distribution of pigments in several organs. The results showed two major types of porphyrin-like pigments, yellowish and greenish in colour, that are chiefly stored as intraplasmatic granules. Whereas the proboscis holds yellow pigments, the skin harbours both types in highly specialised cells. In their turn, oocytes and intestine have mostly green pigments. Despite some inter-individual variation, the pigments tend to be stable after prolonged storage at −20 °C, which has important implications for future studies. The results show that, in a foraging predator of the intertidal where melanins are circumscribed to lining the nervous system, porphyrinoid pigments have a key role in protection against UV light, in sensing and even as chemical defence against foulants and predators, which represents a remarkable adaptive feature.

Ultrastructural Analysis of Human Gallstones using Synchrotron Radiation µCT.

Gallstone formation is a pathological process of mineralization in the human body. Determination of the morphology and ultrastructure of gallstones holds the key to understanding the pathophysiology of gallbladder disease. Synchrotron radiation phase-contrast Xray microtomography is a novel technology, which is designed for comprehensive analysis of gallstone ultrastructure. Nine human gallstones were obtained from the Department of Pathology, Qingpu branch of Zhongshan Hospital Affiliated to Fudan University (China), and scanned by synchrotron radiation µCT (SR µCT). The imaging data generated by SR µCT scan were analyzed. The three-dimensional ultrastructure of human gallstones corresponding to their cholesterol and bile pigment composition was determined. The ultrastructure of gallstones exhibits considerable diversity and complexity. The synchrotron radiation phase-contrast X-ray microtomography is a valuable tool for in-depth study of human gallstones.

Residual cavity hydrops initially misdiagnosed as recurrent hepatic echinococcosis

A 37-year-old woman presented to our liver surgery clinic with a 12-month history of intermittent pain in the right upper quadrant of the abdomen. More than 5 years earlier, the patient had undergone routine excision of the internal capsule because of a hepatic hydatid cyst and had taken albendazole regularly after surgery (300 mg every 12 h for 6 months). A large heteroechoic hepatic mass was identified by abdominal ultrasound. Laboratory tests showed a normal white blood cell count, a normal absolute eosinophil count, and negative anti-echinococcus IgG antibody status. A CT scan showed a 5-cm low-density mass with calcification in the anterior superior segment of the right lobe of the liver, which suggested recurrence of liver hydatid cyst (figure). The patient had a laparotomy, during which the entire cyst was removed intact. The cyst wall was white and contained a small amount of bile and pigmented stones. Pathological testing showed intrahepatic cystic degeneration of liver tissue, and a large amount of bile pigment deposition inside the cyst wall. Echinococcus granulosus was not detected. At follow-up 6 months after surgery, the patient had no residual symptoms.

Effects of Acute Concentrations of Vestaline<sup>®</sup> (pendimethalin) Herbicide on Histopathology of Liver and Gills of Exposed <i>Clarias gariepinus</i> Juveniles

This study was carried out to determine histopathological damages of liver and gills caused by acute concentrations of vestaline®(pendimethalin) herbicide on Clarias gariepinus using96-hour bioassay test. The toxicity was carried out using 180 healthy fish of mean weight 27.97±0.03g which were divided into six treatments with each treatment having ten fish and the setup was in triplicate. The concentrations of Vestaline®(pendimethalin) herbicide used were (0.0mg/l, 33mg/l, 82.5mg/l,115.5mg/l,148.5mg/l and 181.5mg/l). After the 96-hours, both gills and liver of the fish were removed from dead fish. Photomicrographs of the histological slides were taken.Histology of the liver in control sample showed normal hepatic tissue (Hepatocytes with granular cytoplasm) and round nucleus. Histology of the gills in control sample showed normal structure of the filaments and lamellae. The histology of the exposedliver Showed vacoulation of cytoplasm, rapture of hepatocytes, bile pigment disintegration, necrosis and cytoplasmic degeneration while the histology ofgills exposed to different concentrations of vestaline®(pendimethalin) herbicide showed marked distortion of the gills lamellae, hyperplasia of lamellar epithelium and necrosis. The acute concentrations confirmed that vestaline®(pendimethalin) herbicide is highly toxic to Clarias garienpinus and showed heightened damages at higher concentrations.

Comparative histomorphological study of non affected and affected bile duct and gall bladder by fascioliasis in Black Bengal Goat

The purpose of this study was to comparative histomorphological investigation of the non affected and affected bile duct and gall bladder by fascioliasis in Black Bengal goat. The average weight of affected gall bladder was 26.10±0.70 gm which was significantly (p<0.001) higher than non affected gall bladder (19.40±0.96 gm). The average length and girth of affected gall bladder were 10.30±0.37 cm and 8.24±0.30 cm, respectively which were also significantly (p<0.001) higher than the length (6.10±0.30 cm) and Girth (5.85±0.25 cm) of non-affected gall bladder of Black Bengal Goat. The gross changes in acute form, thickening of the bile ducts and fibrosis in a portal area due to chronic fascioliasis was found in case of affected bile duct but were not found in case of non affected liver. A brownish exudates and a number of mature Fasciola gigantica were found in the lumen. The adult Fasciola gigantica was noticed in cross section in the lumen of the thickened bile ducts. Acute pathological lesions could only be produced by developing flukes prior to their entry to the bile ducts. Microscopically the epithelial layer of the bile ducts were seen to the partially disintegrated, but simultaneous proliferation of epithelial cells occurred. Thickening of the bile ducts was the result of connective tissue proliferation. Deposition of bile pigment in the tissue space and bile duct in some parts showed periductal cellular infiltrations, mainly neutrophiles, lymphocyte and eosinophiles. No calcification in the wall of the bile ducts in chronic Fascioliasis in goat could be seen in this study. The gall bladder was very dark usually contained blood clots, the consistency of bile was also very dense. Microcopically hyperplasia of the tubuloalveolar glands and numerous eggs were seen in the bile of infected goat which were absence in case of non infected goat.
 Asian J. Med. Biol. Res. December 2018, 4(4): 406-415

A deep learning model for predicting chemical composition of gallstones with big data in medical Internet of Things

In this paper, we present a deep learning model for potentially diagnosing gallbladder stone with big data from medical Internet of Things. With the increasing trend of population aging and the change of people’s living habits, gallbladder stone is increasingly common around the world. Specially, gallstones can be classified into four types, i.e., cholesterol stones, bile pigment stones, mixed stones and other rare stones, based on the chemical composition of gallstones. Furthermore, the chemical composition directly determines the treatment options. Currently, medical Internet of Things enables the collection of big medical data from massive ultrasonic images, computed tomography and magnetic resonance imaging of gallstones. However, it is a challenging issue to determine the exact chemical composition of gallstones from the collected big medical data. To tackle this issue, this paper presents a convolutional neural network to potentially learn the features of the collected data. Furthermore, we describe an effective learning approach for training the developed convolutional neural network. Finally, we analyze the characteristics of different types of gallstones, which can help improve our presented model to potentially determine the chemical composition of gallstones. The presented model can potentially obtain smart medical data from medical Internet of Things for assisted diagnose and treatment recommendation of gallbladder stones, aiming to build smart Internet of Things, especially smart health.

Proton Pump Inhibitor-Induced Liver Injury

Proton Pump Inhibitors (PPIs) are one of the most widely prescribed medications in the world and for a long time they were regarded as one of the safest medications. Recent studies have linked them with numerous adverse effects like dementia, interstitial nephritis, bone fractures, clostridium difficile infection, pneumonia etc. however, acute liver injury is not one of them. A 65-year-old female with no known liver disease presented with jaundice, dark urine and light stool 3 days after starting esomeprazole for heartburn which prompted her to stop the medication and seek medical attention. Outpatient laboratory studies were significant for total bilirubin of 12.4 mg/dl, AST 374 U/L, ALT 678 U/L, ALP 114 U/L and INR of 2. The patient was promptly sent to emergency department by her primary physician for further evaluation. Her mental status remained intact. Inpatient studies showed consistent elevation of liver test as well as positive ANA (antinuclear antibody) of 1:320 and AMA (antimitochondrial antibody) of 1:20. Due to concern for drug induced liver injury and possible autoimmune liver disease given positive autoimmune markers, liver biopsy was performed which showed acute cholestatic hepatitis compatible with drug induced liver injury (DILI). The patient's serum aminotransferase levels improved to AST 113 U/L, ALT 278 U/L respectively and total bilirubin of 10 upon discharge. At outpatient visit 6 week later, her labs were back to normal. DILI is one of the most common causes of acute hepatitis in the United States. Majority of the studies have not documented association of PPIs with liver injury. However, a few cases of PPI induced liver injury with minor elevation of liver enzymes which normalized after discontinuation of PPI have been documented. Omeprazole and pantoprazole are the main culprits among the PPIs but there are a few cases associated with esomeprazole as well. To our knowledge this is the first case of biopsy proven acute liver injury caused by esomeprazole. DILI may cause serious liver failure which warrants early diagnosis and treatment including referral to liver transplantation. Our case provides a convincing evidence that esomeprazole linked to acute liver injury. Once thought the safest and the most prescribed group of medications, is it time to add one more adverse effect on their extensive list of adverse effects?2422_A Figure 1. The normal architecture of the liver is preserved without scarring. There is marked portal and lobular inflammatory infiltrates and mild steatosis.2422_B Figure 2. Portal tracts contain a mild mixed inflammatory infiltrate including eosinophils (thin arrow). Lobular hepatitis is evidenced by collections of pigment laden macrophages (angled arrow), focal mixed inflammatory infiltrates and scattered acidophil bodies (thick arrow)2422_C Figure 3. Cholestatic features are evidenced by prominent bilirubinostasis in zone 3 hepatocytes (thin arrow), focal canalicular bile plugs (thick arrow), and bile pigment in macrophages (angled arrow).

A CASE STUDY ON THE AYURVEDIC MANAGEMENT OF BAHUPITTA KAMALA WSR JAUNDICE

Modern culture and advanced technology have made life comfortable, but it’s given invitation to many diseases. In fast life style of people are leading irregular eating habits, eating outside has become fashion which increased risk of contaminated food and water. All these etiological factors lead to risk of related disorders. Bahupitta kamla is one of important disease. Jaundice is a condition in which yellowness of skin, sclera, mucus membrane, and excretions occurs due to hyperbilirubinemia and depositions of bile pigments.
 Jaundice is described as kamala vyadhi in Ayurveda. IN ayurvedic samhita description of kamala is given in detail. The description of hepatocellular jaundice is similar to ayurvedic description of kamala vyadhi. Here a case report of a 30 years male having Bahupitta Kamala (Jaundice) who was treated with ayurvedic medicine and some panchakarma which give effective results with ayurvedic management.

Effective Treatment of Chronic Proliferative Cholangitis by Local Gentamicin Infusion in Rabbits.

Background Hepatolithiasis is highly prevalent in East Asia characterized by the presence of gallstones in the biliary ducts of the liver. Surgical resection is the potentially curative treatment but bears a high risk of stone recurrence and biliary restenosis. This is closely related to the universal presence of chronic proliferative cholangitis (CPC) in the majority of patients. Recent evidence has indicated the association of bacterial infection with the development of CPC in hepatolithiasis. Thus, this study aims to investigate the feasibility and efficacy of local infusion of gentamicin (an antibiotic) for the treatment of CPC in a rabbit model. Methods The rabbit CPC model was established based on previously published protocols. Bile duct samples were collected from gentamicin-treated or control animals for pathological and molecular characterization. Results Histologically, the hyperplasia of biliary epithelium and submucosal glands were inhibited and the thickness of the bile duct wall was significantly decreased after gentamicin therapy. Consistently, the percentage of proliferating cells marked by ki67 was significantly reduced by the treatment. More importantly, this treatment inhibited interleukin 2 production, an essential inflammatory cytokine, and the enzyme activity of endogenous β-Glucuronidase, a key factor in the formation of bile pigment. Conclusions Local gentamicin infusion effectively inhibits the inflammation, cell proliferation, and lithogenesis in a rabbit model of CPC. This approach represents a potential treatment for CPC and thus prevents recurrent hepatolithiasis.

Crawly critters’ mysteries and marvels

Green-blooded mystery New Guinea lizards taste kind of like bad sushi, according to biologist and apparently adventurous diner Christopher C. Austin. Louisiana State University’s Austin was a graduate student when he snacked on the raw lizards—one with red blood and one with exotic green blood—to test a hypothesis. Perhaps green-blooded lizards tasted worse to predators than red-blooded ones, giving them an evolutionary edge that might explain how some lizard species got green. The peculiar color, which paints the lizards’ bones, tongues, and tissues lime green, comes from the bile pigment biliverdin. Too much biliverdin in blood leads to illnesses such as jaundice in humans and other vertebrates, yet the green-blooded lizards can stand shockingly high levels of the bile. As for the edible experiment, Austin found that both types of lizards tasted about the same: “not horrible.” His hypothesis was ultimately “squashed” when later experiments showed that the lizards’ natural