Therapeutic effect of yinchenhao decoction on cholelithiasis via mucin in the gallbladder and intestine.

Cholelithiasis is a common and frequently occurring disease worldwide that belongs to the category of jaundice in traditional Chinese medicine. Yinchenhao decoction (YD) consists of Artemisia capillaris Thunb., Gardenia jasminoides J.Ellis, and Rheum palmatum L., and is traditionally used to treat jaundice, which has a significant therapeutic effect on cholelithiasis. Our study aimed to investigate the pathological mechanism of cholelithiasis and the therapeutic mechanism of YD via mucin in the gallbladder and intestine. YD was prepared and analyzed using HPLC. The supersaturation stability experiment was designed by the solvent-shift method. The cell transport experiment was conducted by coculture monolayers. The animal experiment was performed using a cholelithiasis model with a high-cholesterol diet. The related indicators were detected by automatic biochemical analyzer, PCR, western blot, or ELISA. Statistics were analyzed using χ2-tests and t-tests. As the results, in cholelithiasis, MUC5AC highly expressed in the gallbladder shortened cholesterol supersaturation and promoted cholesterol crystallization via the inflammatory cytokine signaling pathway; MUC2 highly expressed in the small intestine prolonged cholesterol supersaturation and promoted cholesterol absorption via the inflammatory cytokine signaling pathway. YD inhibited mucin expression in the gallbladder and intestine in a concentration-dependent manner for cholelithiasis treatment by inhibiting the inflammatory cytokine signaling pathway, which was attributed to the active components, including chlorogenic acid, geniposide, and rhein.

[Nutritional intervention in the control of gallstones and renal lithiasis]. / Intervención nutricional en el control de la colelitiasis y la litiasis renal.

INTRODUCTION: Cholelithiasis and kidney stones are frequent pathologies in developed countries. Gallstones can be pigmentary, cholesterol (75%) or mixed. Age, female sex, obesity, rapid weight loss, consumption of refined sugars, saturated fat, iron deficiency, vitamin D and low intake of fiber and vitamin C are factors associated with an increased risk of cholelithiasis. On the other hand, the intake of ω-3 fatty acids, oleic acid, calcium, magnesium, fiber, fruits and vegetables, dairy products, nuts, coffee, moderate consumption of alcohol, vitamin C supplements, physical exercise and a regular diet have a protective paper. The most frequent kidney stones are calcium oxalate followed by mixed ones (oxalate and calcium phosphate), struvite, uric acid and cystine. A high water intake is recommended (> 2.5 l / day), varying the type of recommended or unadvisable food depending on the type of calculus. In oxalic lithiasis it is recommended to reduce the consumption of meat, moderate that of spinach, Swiss chard, asparagus, chocolate and avoid excessive sodium intake. The administration of oxalate-degrading probiotics (Lactobacillus) may reduce intestinal absorption, although further studies are necessary to corroborate these results. In calcium phosphate acidifying diet is recommended and limit the consumption of coffee and tea. The prevention of uric calculus is based on hydration with alkalizing drinks and vegetarian diet, decreasing foods rich in purines (liver, kidney, fish eggs, anchovies, sardines and seafood) and in calculus of cystine diet is recommended alkalizing. Since the formation of struvite calculi is due to urinary infections, pharmacological treatment and the consumption of acidifying diets, moderation of the intake of phosphate-rich foods and limiting the contribution of fats and citrus fruits are necessary. The nutritional intervention is an effective measure in the prevention of biliary and renal lithiasis and prevent its recurrence.

INTRODUCCIÓN: La colelitiasis y litiasis renal son patologías frecuentes en países desarrollados. Los cálculos biliares pueden ser pigmentarios, de colesterol (75%) o mixtos. La edad, el sexo femenino, la obesidad, la pérdida rápida de peso, el consumo de azúcares refinados, la grasa saturada, la deficiencia de hierro y de vitamina D y la baja ingesta de fibra y vitamina C son factores asociados a mayor riesgo de colelitiasis. Por otro lado, la ingesta de ácidos grasos ω-3, ácido oleico, calcio, magnesio, fibra, frutas y verduras, lácteos, frutos secos, café, un consumo moderado de alcohol, suplementos de vitamina C, ejercicio físico y una alimentación regular desempeñan un papel protector. Las litiasis renales más frecuentes son de oxalato cálcico, seguidas de las mixtas (oxalato y fosfato cálcico), estruvita, ácido úrico y cistina. Se aconseja una elevada ingesta hídrica (> 2,5 l/día), variando el tipo de alimentos recomendados o desaconsejados en función del tipo de cálculo. En litiasis oxálica se recomienda reducir el consumo de carne, moderar el de espinacas, acelgas, espárragos, chocolate y evitar el aporte excesivo de sodio. La administración de probióticos degradantes de oxalato (Lactobacillus) podría reducir su absorción intestinal, aunque son necesarios más estudios para corroborar estos resultados. En las de fosfato cálcico se aconseja dieta acidificante y limitar el consumo de café y té. La prevención de cálculos de úrico está basada en la hidratación con bebidas alcalinizantes y dieta vegetariana, disminuyendo los alimentos ricos en purinas (hígado, riñón, huevas de pescado, anchoas, sardinas y mariscos), y en cálculos de cistina se aconseja el consumo de dietas alcalinizantes. Dado que la formación de cálculos de estruvita se debe a infecciones urinarias, es necesario un tratamiento farmacológico y el consumo de dietas acidificantes, moderar la ingesta de alimentos ricos en fosfatos y limitar el aporte de grasas y cítricos. La intervención nutricional es una medida eficaz en la prevención de la litiasis biliar y renal y para evitar su recurrencia.

[Effects of vitamin C administration on cholesterol gallstone formation]. / Efecto de la ingesta de vitamina C en el proceso de formación de cálculos biliares de colesterol.

BACKGROUND: Biliary cholesterol is transported by vesicles and micelles. Cholesterol microcrystals are derived from thermodynamically unstable vesicles. In experimental animals vitamin C deficiency leads to a super-saturation of biliary cholesterol and to the formation of gallstones. AIM: To search for a possible relationship between serum levels of vitamin C and the formation of cholesterol gallstones in patients with cholelithiasis. MATERIAL AND METHODS: Thirteen patients with cholelithiasis and a programmed surgical intervention were treated with 2 g/day of vitamin C per os for two weeks before surgery. Forty nine patients subjected to a cholecystectomy not supplemented with vitamin C were studied as controls. Plasma concentrations of vitamin C and lipid profiles were measured. The cholesterol saturation index, crystallization time, cholesterol and phospholipid content in vesicles and micelles, separated by gel filtration chromatography, were studied in bile samples obtained from the gallbladder. RESULTS: Vitamin C supplementation did not change significantly plasma lipids and bile lipid concentrations. However, in supplemented patients, significant reductions in vesicular cholesterol content (6.5 ± 4.8% compared to 17.9 ± 14.0% in the control group; p < 0.05) and vesicular cholesterol/phospholipid ratio (0.71 ± 0.53 compared to 1.36 ± 1.15 in controls; p < 0.05), were observed. CONCLUSIONS: Vitamin C administration may modify bile cholesterol crystallization process, the first step in cholesterol gallstone formation.

Efecto de la ingesta de vitamina C en el proceso de formación de cálculos biliares de colesterol / Effects of vitamin C administration on cholesterol gallstone formation

Background: Biliary cholesterol is transported by vesicles and micelles. Cholesterol microcrystals are derived from thermodynamically unstable vesicles. In experimental animals vitamin C deficiency leads to a super-saturation of biliary cholesterol and to the formation of gallstones. Aim: To search for a possible relationship between serum levels of vitamin C and the formation of cholesterol gallstones in patients with cholelithiasis. Material and Methods: Thirteen patients with cholelithiasis and a programmed surgical intervention were treated with 2 g/day of vitamin C per os for two weeks before surgery. Forty nine patients subjected to a cholecystectomy not supplemented with vitamin C were studied as controls. Plasma concentrations of vitamin C and lipid profiles were measured. The cholesterol saturation index, crystallization time, cholesterol and phospholipid content in vesicles and micelles, separated by gel filtration chromatography, were studied in bile samples obtained from the gallbladder. Results: Vitamin C supplementation did not change significantly plasma lipids and bile lipid concentrations. However, in supplemented patients, significant reductions in vesicular cholesterol content (6.5 ± 4.8% compared to 17.9 ± 14.0% in the control group; p < 0.05) and vesicular cholesterol/phospholipid ratio (0.71 ± 0.53 compared to 1.36 ± 1.15 in controls; p < 0.05), were observed. Conclusions: Vitamin C administration may modify bile cholesterol crystallization process, the first step in cholesterol gallstone formation.

Is ritonavir-boosted atazanavir a risk for cholelithiasis compared to other protease inhibitors?

OBJECTIVE: To compare the incidence of complicated cholelithiasis in patients receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy with those on other protease inhibitors (PIs). DESIGN: We conducted a single-center retrospective cohort study of patients who started either ritonavir-boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing antiretroviral therapy. METHODS: The incidence of complicated cholelithiasis was determined in each group. Complicated cholelithiasis was defined as follows: 1) cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2) symptomatic cholelithiasis or choledocholithiasis which required invasive procedures such as cholecystomy and endoscopic retrograde cholangiopancreatography. The effects of ATV/r were estimated by univariate and multivariate Cox hazards models as the primary exposure. RESULTS: Complicated cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group (n = 776), respectively. The incidence was not statistically different in the two groups by log-rank test (P = 0.702). By univariate and multivariate analysis adjusted for age and body weight, ATV/r use was not associated with cholelithiasis. (HR = 1.365; 95% CI, 0.275-6.775; p = 0.704) (adjusted HR = 1.390; 95% CI, 0.276-7.017; p = 0.690). For the 3 patients who developed cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis was 18, 34, and 39 months, respectively. CONCLUSION: In this study, the incidence of complicated cholelithiasis was low and was not different between patients on ATV/r and those on other PIs. On the contrary to ATV/r-associated nephrolithiasis, the possible risk of cholelithiasis should not preclude the use of ATV/r.

Comparative proteomic analysis of gallbladder bile proteins related to cholesterol gallstones.

BACKGROUND: Nucleation of cholesterol monohydrate crystals following the aggregation and fusion of cholesterol-enriched vesicles is a critical procedure in the formation of cholesterol gallstone. Biliary proteins play important roles in the process. It is inefficient to screen pro-nucleating or anti-nucleating proteins with routine physiochemical techniques, by which we discovered several pro-nucleating proteins. METHODOLOGY/PRINCIPAL FINDINGS: Based on comparative proteomic technologies, we investigated the differentially expressed proteins between the cholesterol gallstone and control groups, and between the vesicular phase and micellar phase. There are 401±75 spots detected on the cholesterol gallstone group and 389±94 spots on the control group gels, 120±24 spots detected on vesicular phase and 198±37 on micellar phase gels, and accordingly 22 and 8 differentially expressed proteins were identified successfully, respectively. Three of them, HSA, Profilin and Retinol Binding Protein, were validated by Western blot. CONCLUSION/SIGNIFICANCE: Some of the identified proteins are in good agreement with proteins reported to be involved in the gallstone formation before. The information from this study might provide some important clues to uncover the key proteins involved in the formation of cholesterol gallstone.

Concerted spatial-frequency and polarization-phase filtering of laser images of polycrystalline networks of blood plasma smears.

The complex technique of concerted polarization-phase and spatial-frequency filtering of blood plasma laser images is suggested. The possibility of obtaining the coordinate distributions of phases of linearly and circularly birefringent protein networks of blood plasma separately is presented. The statistical (moments of the first to fourth orders) and scale self-similar (logarithmic dependences of power spectra) structure of phase maps of different types of birefringence of blood plasma of two groups of patients--healthy people (donors) and those suffering from rectal cancer--is investigated. The diagnostically sensitive parameters of a pathological change of the birefringence of blood plasma polycrystalline networks are determined. The effectiveness of this technique for detecting change in birefringence in the smears of other biological fluids in diagnosing the appearance of cholelithiasis (bile), operative differentiation of the acute and gangrenous appendicitis (exudate), and differentiation of inflammatory diseases of joints (synovial fluid) is shown.

Role of nicotine in gallbladder carcinoma: a preliminary report.

OBJECTIVE: To assess the role of nicotine in gallbladder carcinoma and its association with the stage and degree of cancer differentiation. METHODS: Tissue samples from gallbladder were obtained from 20 patients with gallbladder cancer and 20 age- and gender-matched patients with cholelithiasis who served as the control group. Gallbladder tissue (2 g) was extracted and analyzed for nicotine content using capillary gas chromatography. Nitrogen was used as the carrier gas. Standard curves of nicotine in methanol were made by injecting the internal standards. RESULTS: A significantly higher tissue nicotine concentration was observed in the gallbladder carcinoma group than that in the control group (179.63 ng/mg vs 6.00 ng/mg, P < 0.001). The stage and degree of cancer differentiation did not seem to affect the nicotine levels. Gallbladder tissue contained a significantly higher nicotine concentration in smokers with cancer compared with those in the control group (1570.00 ng/mg vs 232.25 ng/mg, P < 0.001). Interestingly, non-smokers in cancer group also had a higher nicotine concentration than the control group (161.50 ng/mg vs 4.00 ng/mg, P = 0.002). CONCLUSION: Nicotine is selectively concentrated in malignant gallbladder tissue irrespective of smoking status, showing its strong association with gallbladder cancer.

[Regulation of calculus bovis on the function of mice oral fibroblasts].

To explore the influence of calculus bovis on the function of primary cultured mice oral fibroblasts, we determined the effects of calculus bovis on the fibroblast proliferation, collagen production, matrix metalloproteinases-2, -9 activities and tissue inhibitor of metalloproteinase-1 production by MTT assay, chloramine T method, gelatin zymography and enzyme-linked immunosorbent assays respectively. The results showed that calculus bovis could significantly inhibit the proliferation of fibroblasts and collagen synthesis in a concentration dependent manner, could significantly (P<0.05) suppress matrix metalloproteinases-2 activity and very significantly (P<0.01) inhibit the production of tissue inhibitor of metalloproteinase-1. In conclusion, the major function of calculus bovis in the process of ulcer healing is not to promote tissue regeneration, the mechanism that calculus bovis inhibits collagen synthesis may be partly due to its ability to very significantly (P<0.01) suppress the production of tissue inhibitor of metalloproteinase-1.

Variational study of the constituents of cholesterol stones by laser-induced breakdown spectroscopy.

The major and minor constituents of cholesterol gallstones were investigated by Laser-induced breakdown spectroscopy. The elements detected in the center and in the shell part were calcium (Ca), carbon (C), copper (Cu), hydrogen (H), magnesium (Mg), nitrogen (N), sodium (Na), oxygen (O) and potassium (K), but Cu was absent from the surface of the cholesterol gallstones. Our experimental results revealed that calcium was a major constituent of cholesterol gallstones. Our results also showed that the concentration of Ca, Cu and Mg were large in the center in comparison with the shell. Laser-induced breakdown (LIB) spectra of both portions of the surface (colored part and discolored part) of the cholesterol gallstones were recorded. The concentrations of sodium and potassium were higher in the non-pigmented (colored) part than in the pigmented part (discolored/pigment), which showed that the deficiency of sodium and potassium was playing a key role in the formation of discoloration at the different locations on the outer surfaces of the cholesterol gallstones. Thus, laser-induced breakdown spectroscopy (LIBS) is a suitable technique for the analysis of cholesterol gallstones without any sample preparation.

Calcium carbonate gallstones in children.

BACKGROUND: In the United States, cholesterol stones account for 70% to 95% of adult gallstones and black pigment stones for most of the remainder. Calcium carbonate stones are exceptionally rare. A previous analysis of a small number of pediatric gallstones from the north of England showed a remarkably high prevalence of calcium carbonate stones. The aims of this study were to analyze a much larger series of pediatric gallstones from our region and to compare their chemical composition with a series of adult gallstones from the same geographic area. METHODS: A consecutive series of gallbladder stones from 63 children and 50 adults from the north of England were analyzed in detail using Fourier transform infrared microspectroscopy. Demographic and clinical data were collected on all patients. The relative proportions of each major stone component were assessed: cholesterol, protein and calcium salts of bilirubin, fatty acids, calcium carbonate, and hydroxyapatite. RESULTS: Thirty-nine (78%) adults had typical cholesterol stones, 7 (14%) had black pigment bilirubinate stones, and only 2 (4%) had calcium carbonate stones. In contrast, 30 (48%) children had black pigment stones, 13 (21%) had cholesterol stones, 15 (24%) had calcium carbonate stones, 3 (5%) had protein dominant stones, and 2 (3%) had brown pigment stones. In children, cholesterol stones were more likely in overweight adolescent girls with a family history of gallstones, whereas black pigment stones were equally common in boys and girls and associated with hemolysis, parenteral nutrition, and neonatal abdominal surgery. Calcium carbonate stones were more common in boys, and almost half had undergone neonatal abdominal surgery and/or required neonatal intensive care. CONCLUSION: The composition of pediatric gallstones differs significantly from that found in adults. In particular, one quarter of the children in this series had calcium carbonate stones, previously considered rare. Geographic differences are not the major reason for the high prevalence of calcium carbonate gallstones in children.

When is pancreatitis considered to be of biliary origin and what are the implications for management?

Acute pancreatitis is a disease caused by gallstones in 40-60% of patients. Identification of these patients is extremely important, since there are specific therapeutic interventions by endoscopic sphincterotomy and/or cholecystectomy. The combination of trans-abdominal ultrasound (stones in the gallbladder and/or main bile duct) and elevated serum alanine transaminase (circa >60 IU/l within 48 h of presentation) indicates gallstones as the cause in the majority of patients with acute pancreatitis. In the presence of a severe attack this is a strong indication for intervention by endoscopic sphincterotomy. The presence of a significant main bile duct dilatation is also strongly indicative of gallstones and should prompt the use of endoluminal ultrasonography: >8 mm diameter with gallbladder in situ, or >10 mm following cholecystectomy if aged <70 years and >12 mm, respectively, if > or = 70 years. In mild pancreatitis surgically fit patients should be treated by cholecystectomy, and intra-operative cholangiography, as pre-operative biliary imaging is not efficient in this setting. Patients who are not fit for cholecystectomy should undergo prophylactic endoscopic sphincterotomy to prevent further attacks. In the post-acute-phase, pancreatitis patients in whom the aetiology is uncertain should undergo endoluminal ultrasonography. Thisis the most sensitive method for the detection of cholelithiasis and choledocholithiasis and may reveal alternative aetiological factors such as a small ampullary or pancreatic cancer. A number of recent studies have shown that bile crystal analysis, a marker for microlithiasis, increases the yield of positive results over and above endoluminal ultrasonography, and should be considered as part of the modern investigative algorithm.

[Pathophysiology of biliary lithiasis]. / Physiopathologie de la lithiase biliaire.

Gallstones affect about 15% of adults in Europe. Cholesterol gallstone is the common form of the disease. Pigment stones, resulting from bilirubin precipitation feature particular clinical settings such as chronic hemolysis, intestinal malabsorption and various biliary tract diseases. Supersaturation of bile with cholesterol, increased formation of deoxycholic acid and gallbladder hypomotility are the main factors involved in gallstones pathogenesis.

Gallstone disease: Microlithiasis and sludge.

'Sludge' is the solid material which results from the slow settling of particles dispersed in a liquid medium. Biliary sludge in the gallbladder can be detected by transabdominal ultrasonography, and the typical echoes derive mainly from pigment precipitates mixed with cholesterol crystals. A portion of biliary sludge contains comparatively large particles (1-3 mm) called microliths, the formation of which is an obligatory intermediate step in the development of all types of gallstone. Microlithiasis and sludge in bile may cause colicky pain, cholecystitis, cholangitis, and acute pancreatitis, and are thus of clinical relevance. In these patients treatment follows the guidelines of symptomatic gallstone disease, and strategies include long-term application of ursodeoxycholic acid, endoscopic papillotomy, or preferably laparoscopic cholecystectomy.

Serum adiponectin levels in cholesterol and pigment cholelithiasis.

BACKGROUND: Altered adiponectin levels are associated with metabolic abnormalities. The aim of this study was to explore the role of adiponectin in cholelithiasis. METHODS: A radioimmunoassay was used to determine serum adiponectin levels in 58 patients with cholesterol gallstones and 47 with pigment gallstones, and 101 healthy controls. The chemical composition of extracted gallstones was determined by Fourier transform infrared spectroscopy. RESULTS: The mean(s.d.) adiponectin level was decreased in patients with cholesterol gallstones (7.6(4.1) microg/ml; P < 0.001) but raised in patients with pigment gallstones (17.9(9.0) microg/ml; P < 0.001) in comparison with healthy controls (11.7(6.5) microg/ml). Decreased adiponectin levels (odds ratio (OR) 0.85 (95 per cent confidence interval (c.i.) 0.76 to 0.96); P = 0.008) and female sex (OR 6.06 (95 per cent c.i. 2.10 to 17.46); P = 0.001) were associated with cholesterol gallstone formation. Increased adiponectin levels (OR 1.11 (95 per cent c.i. 1.01 to 1.22); P = 0.025) and increased age (OR 1.06 (95 per cent c.i. 1.01 to 1.12); P = 0.029) were associated with pigment gallstone formation. Raised serum aspartate aminotransferase concentration was a risk factor for both cholesterol (OR 1.16 (95 per cent c.i. 1.03 to 1.30); P = 0.013) and pigment (OR 1.23 (95 per cent c.i. 1.10 to 1.38); P < 0.001) gallstones. CONCLUSION: Gallstone formation is associated with altered serum adiponectin levels. Serum adiponectin might serve as a novel marker for cholesterol and pigment cholelithiasis.

Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis.

OBJECTIVE: Aberrant expression of maspin protein related to DNA hypomethylation in the promoter region is frequently observed in gallbladder carcinomas, whereas the non-tumorous gallbladder epithelium is maspin negative. We investigated maspin expression in non-tumorous gallbladder epithelium in patients with cholelithiasis. METHODS: An immunohistochemical study of maspin expression was performed in 69 patients with cholelithiasis and 30 patients with gastric cancer without cholelithiasis. RESULTS: Immunoreactivity for maspin was observed in focal and patchy regions of the gallbladder epithelium. Positive immunoreactivity for maspin was significantly associated with the presence of intestinal metaplasia in patients with cholelithiasis (p<0.05). CONCLUSION: The high incidence of aberrant maspin expression in both intestinal metaplasia and carcinoma of the gallbladder supports the assumption that intestinal metaplasia of the gallbladder may predispose to gallbladder carcinoma.

[Inhibiting effects of recipe for dispersing stagnated liver qi to promote bile flow on cholesterol gallstone formation in guinea pigs].

OBJECTIVE: To explore the mechanism of the inhibiting effects of recipe for dispersing stagnated liver qi to promote bile flow (Danshijing Tablets) on cholesterol gallstone formation and provide experimental evidence for its clinical application. METHODS: Eighty guinea pigs were randomly divided into 4 groups, which were normal control group, untreated group, ursodeoxycholic acid (UDCA)-treated group and Danshijing Tablets-treated group. The gallstones in guinea pigs were induced by high-cholesterol diet. UDCA and Danshijing Tablets were given orally to guinea pigs in the corresponding group respectively for seven weeks. Then the physical signs of the guinea pigs, the rates of gallstone formation and the histomorphological changes of the gallbladder were examined. RESULTS: The behavior of guinea pigs in the Danshijing Tablets-treated group was obviously improved and the rate of gallstone formation was significantly decreased as compared with those in both untreated and UDCA-treated groups (P<0.05). The inflammation reaction of mucous membrane in gallbladder was evidently reduced in the Danshijing Tablets-treated group and its morphological appearance turned to be approximately normal. CONCLUSION: Recipe for dispersing stagnated liver qi to promote bile flow may decrease gallstone formation. Its mechanism may be related to reducing pathologic changes in gallbladder tissues, which will reduce the damages of cholesterol to the smooth muscle in gallbladder and enhance the contractility of gallbladder.

Tratamento clínico da litíase biliar e hipocondria / Clinical treatment of biliary lithiasis and hypochondria

Além das indicações fundamentais para se obter a dissolução clínica da litíase biliar, sabe-se por experiência que a constância na tomada da medicação é também fundamental para o sucesso do tratamento. Acompanhado pacientes em uso de medicação para dissolução dos cálculos, o autor verificou casos em que a não tomada (esquecimento) por apenas três dias já causa aumento da consistência estrutural dos cálculos no controle radiológico. O hipocondríaco, que é fascinado pelo uso de remédios, apresenta a característica da prazerosa constância na tomada de medicações. O levantamento de 30 casos seqüenciais de pacientes submetidos à dissolução considerados hipocondríacos, comparados com o mesmo número de pessoas mais equilibradas, mostrou significativa diferença. O autor obteve a dissolução completa nos 30 casos de hipocontríacos, enquanto que no grupo de controle a dissolução foi verificada em 19 casos

[Multiple enterolithiasis, coexisting with bladder and gallbladder lithiasis, associated with colon adenocarcinoma]. / Enterolitiasis múltiple, coexistiendo con litiasis biliar y vesical, asociada a adenocarcinoma de colon.

Enteroliths are calculi primarily formed in the intestine. Enterolithiasis is a rare condition frequently associated with intestinal stasis. Usually it causes no symptoms in most cases, but it can be an important diagnostic clue in patients presenting intestinal occlusive symptoms. We report a case of multiple enterolithiasis, very infrequent pathology, coexisting with bladder and gall bladder lithiasis in a patient with colon adenocarcinoma. Diagnosis was made by X-rays and CT images. Calculi were analysed by several methods: chemical, infrared spectroscopy, stereoscopic microscopy and atomic emission spectroscopy; they showed that caluli are made up of organic material and whilokita (calcium and magnesium ortophosphate). No risk factors for lithogenesis were found in this patient excluding the intestinal stasis caused by intestinal narrowing as a result of adenocarcinoma. Genetic factors are suggested as main contributors to hyperlithogenesis observed in this patient. The physiopathological conditions were studied in depth and literature about this subject reviewed.

Single and interacting QTLs for cholesterol gallstones revealed in an intercross between mouse strains NZB and SM.

Quantitative trait locus (QTL) mapping was employed to investigate the genetic determinants of cholesterol gallstone formation in a large intercross between mouse strains SM/J (resistant) and NZB/B1NJ (susceptible). Animals consumed a gallstone-promoting diet for 18 weeks. QTL analyses were performed using gallstone weight and gallstone absence/presence as phenotypes; various models were explored for genome scans. We detected seven single QTLs: three new, significant QTLs were named Lith17 [chromosome (Chr) 5, peak=60 cM, LOD=5.4], Lith18 (Chr 5, 76 cM, LOD=4.3), and Lith19 (Chr 8, 0 cM, LOD=5.3); two confirmed QTLs identified previously and were named Lith20 (Chr 9, 44 cM, LOD=2.7) and Lith21 (Chr 10, 24 cM, LOD=2.9); one new, suggestive QTL (Chr 17) remains unnamed. Upon searching for epistatic interactions that contributed to gallstone susceptibility, the final suggestive QTL on Chr 7 was determined to interact significantly with Lith18 and, therefore, was named Lith22 (65 cM). A second interaction was identified between Lith19 and a locus on Chr 11; this QTL was named Lith23 (13 cM). mRNA expression analyses and amino acid haplotype analyses likely eliminated Slc10a2 as a candidate gene for Lith19. The QTLs identified herein largely contributed to gallstone formation rather than gallstone severity. Cloning the genes underlying these murine QTLs should facilitate prediction and cloning of the orthologous human genes.