Supersaturated Bile Research Articles

THERAPEUTIC EFFECT OF ABHAYA LAVANA WITH SHARAPUNKHA KWATHA IN THE MANAGEMENT OF CHOLELITHIASIS – CASE STUDY

Cholelithiasis is a worldwide medical condition, resulting from a combination of several factors like supersaturation of bile with cholesterol, accelerated nucleation of cholesterol monohydrate in bile, and bile stasis or delayed gallbladder emptying. Gallbladder stones present in one of three clinical stages: asymptomatic, symptomatic and with complications. The treatment options for asymptomatic range from no treatment to selective cholecystectomy. Laparoscopic cholecystectomy remains the default option for symptomatic cases. A definite non-invasive management is be a boon in asymptomatic and symptomatic uncomplicated gallstones. Abhaya Lavana is a strategic combination of Kshara & Lavana kalpana described in classical texts. Its indications point towards that this combination has a definite result in cholelithiasis and associated symptoms. Kwatha of Sharapunkha as anupana would definitely help to carry the drug to its site of action. To evaluate the effect of the treatment, A pre-post-test clinical study was conducted among the 13 participants. Clinical Intervention was done with 2g of Abhaya Lavana with 96ml of Sharapunkha Kwatha in the Middle of every Breakfast for 45 Days. Assessment of Subjective Parameters and Associated symptoms were done prior to the intervention and on 15th, 30th and 45th day. Pre and Post Assessment of Primary Objective - USG and Secondary objective - Lipid Profile were Conducted after Study. Safety of the Drug has been assessed by Pre and Post RFT and LFT. This study reveals that combined effect of Abhaya Lavana and Sharapunkha Kwatha is effective in Cholelithiasis and reducing associated symptoms.

Ayurvedic Management of Cholelithiasis (Pittashmari) – A CaseStudy

Gallstone formation, or cholelithiasis, is caused by a number of factors, including supersaturation of bile with cholesterol, accelerated nucleation of cholesterol monohydrate in bile, bile stasis, or delayed gallbladder emptying due to impaired gallbladder motility. After carefully rewriting Ayurvedic scriptures, we find that, because of its resemblance in location and function, the bile secreted from the gallbladder can be compared to the Accha Pitta stated in Ayurveda. We report that a case of cholelithiasis (Pittashmari) in a 31-year-old female patient had been complaining of severe abdominal pain, distension of the abdomen, and vomiting. Oral medications such as Arogyavardhini vati, tablet Trikatu, Kashaya of Trivrit, Katuki, Sanaya, Arghvad, and Daruharidra were administered to the patient for 3 months. A significant response was observed over clinical symptoms and USG reports. Ayurvedic remedies were used to treat the patient for 3 months. This case study demonstrates the efficacy of Ayurvedic treatment for cholelithiasis (Pittashmari). The study reached the conclusion that Ayurvedic therapy was significantly effective in the treatment of cholelithiasis (Pittashmari).

Enterohepatic circulation of bile acids and its role in pathologies of the hepatobiliary system

Enterohepatic circulation of bile acids is a highly regulated process of secretion of these compounds, intestinal reabsorption and reverse transport to the liver. Violation of this process has significant consequences for the homeostasis of the gastrointestinal tract, liver and the whole organism. This process is tightly controlled by regulatory enzymatic reactions with negative feedback, which leads to the maintenance of a pool and adequate homeostasis of bile acids. The main purpose of this article is to consider the mechanism of enterohepatic circulation of bile acids and evaluate their role both in the formation of pathologies of the hepatobiliary system of various origins, and as a predictor of such processes. We searched for original studies in the scientific databases PubMed, Elsevier Science (Scopus) and Clarivate Analytics (Web of Science) over the past 20 years to identify the features of the above processes, after which a formalized content analysis of the found publications was carried out. Theoretically, every factor that disrupts the enterohepatic circulation leads to pathologies of the hepatobiliary system. However, there are still many unknown aspects when it comes to the regulation of bile acid homeostasis in the enterohepatic circulation. In the last few decades, it is believed that the most important prerequisites for the occurrence of hepatopathy are hypersecretion of bile cholesterol and supersaturation of bile with it. An equally important problem is the change in the pool of bile acids, since its various representatives differ both in chemical activity and in the mechanism of action (from cytotoxicity to cytoprotection).

Effects of Biliary Phospholipids on Cholesterol Crystallization and Growth in Gallstone Formation.

The prevalence of cholesterol gallstone disease is increasing, primarily due to the global epidemic of obesity associated with insulin resistance, and this trend leads to a considerable healthcare, financial, and social burden worldwide. Although phospholipids play an essential role in maintaining cholesterol solubility in bile through both mixed micelles and vesicles, little attention has been paid to the impact of biliary phospholipids on the pathogenesis of cholesterol gallstone formation. A reduction or deficiency of biliary phospholipids results in a distinctly abnormal metastable physical-chemical state of bile predisposing to supersaturation with cholesterol. Changes in biliary phospholipid concentrations influence cholesterol crystallization by yielding both liquid crystalline and "anhydrous" crystalline metastable intermediates, evolving into classical parallelogram-shaped cholesterol monohydrate crystals in supersaturated bile. As a result, five distinct crystallization pathways, A-E, have been defined, mainly based on the prime habits of liquid and solid crystals in the physiological or pathophysiological cholesterol saturation of gallbladder and hepatic bile. This review concisely summarizes the chemical structures and physical-chemical properties of biliary phospholipids and their physiological functions in bile formation and cholesterol solubility in bile, as well as comprehensively discusses the latest advances in the role of biliary phospholipids in cholesterol crystallization and growth in gallstone formation, largely based on the findings from clinical and animal studies and in vitro experiments. The insights gleaned from uncovering the cholelithogenic mechanisms are expected to form a fundamental framework for investigating the hitherto elusive events in the earliest stage of cholesterol nucleation and crystallization. This may help to identify better measures for early diagnosis and prevention in susceptible subjects and effective treatment of patients with gallstones.

Gallstone-related complications and evidence base treatments. A scoop review

The incidence of gallstones is 10-15%, making it one of the most common causes of surgical admissions. The number of admissions and operations for gallstone disease is increasing. Commonly gallstones are formed in the gallbladder but can also develop in the biliary tree. Commonly, gallstones are made of cholesterol. Even though the exact cause of supersaturation of bile is not known, there are multiple associate factors for gallstone formation. Most patients with gallstones never experience any symptoms, but the risk of presenting with complications related to gallstones is 1%-4% a year. Patients with gallstones can present with pain or other more severe complications that demand surgical treatment and follow-up. This article looks into epidemiology, basic pathophysiology, complications, pregnancy and gallstones, diagnosis and recent evidence base treatment of gallstone disease.

Gallstones: The thing in itself.

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Adeno-associated virus-based caveolin-1 delivery via different routes for the prevention of cholesterol gallstone formation

BackgroundHepatic caveolin-1 (CAV1) is reduced in cholesterol gallstone disease (CGD). Mice with CAV1 deficiency were prone to develop CGD. However, it remains unknown whether restored hepatic CAV1 expression prevents the development of CGD.MethodsC57BL/6 mice were injected with adeno-associated virus 2/8 (AAV2/8) vectors carrying the CAV1 gene (AAV2/8CAV1) via intravenous (i.v.) or intraperitoneal (i.p.) route and then subjected to a lithogenic diet (LD) for 8 weeks. Uninjected mice were used as controls. The functional consequences of rescuing CAV1 expression by either i.v. or i.p. AAV2/8CAV1 treatment for CGD prevention and its subsequent molecular mechanisms were examined.ResultsCAV1 expression was reduced in the liver and gallbladder of LD-fed CGD mice. We discovered that AAV2/8CAV1 i.p. delivery results in higher transduction efficiency in the gallbladder than tail vein administration. Although either i.v. or i.p. injection of AAV2/8CAV1 improved liver lipid metabolic abnormalities in CGD mice but did not affect LD feeding-induced bile cholesterol supersaturation. In comparison with i.v. administration route, i.p. administration of AAV2/8CAV1 obviously increased CAV1 protein levels in the gallbladder of LD-fed mice, and i.p. delivery of AAV2/8CAV1 partially improved gallbladder cholecystokinin receptor (CCKAR) responsiveness and impeded bile cholesterol nucleation via the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling, which induced a reduction in gallbladder mucin-1 (MUC1) and MUC5ac expression and gallbladder cholesterol accumulation.ConclusionCGD prevention by i.p. AAV2/8CAV1 injection in LD-fed mice was associated with the improvement of gallbladder stasis, which again supported the notion that supersaturated bile is required but not sufficient for the formation of cholesterol gallstones. Additionally, AAV treatment via the local i.p. injection offers particular advantages over the systemic i.v. route for much more effective gallbladder gene delivery, which will be an excellent tool for conducting preclinical functional studies on the maintenance of normal gallbladder function to prevent CGD.

S2843 How Many Stones Are Too Many Stones?

Introduction: Gallstones disease or cholelithiasis has become one of the most prevalent diseases of the developed world in the last few decades. Certain populations, including pregnant females, have been identified to be at increased risk. Gallstones can be present in 1-3% of all pregnancies and acute cholecystitis is the second cause of non-obstetric indication for surgery in pregnancy. In pregnancy, there is an influx of estrogen, which increases cholesterol secretion. By the other side, increased progesterone levels reduce bile secretion and delay gallbladder emptying. These changes result in super-saturation of bile with cholesterol and a predisposition to gallstone formation. We present the case of a postpartum female that presented with cholelithiasis and choledocholithiasis. Case Description/Methods: A 28-year-old female with past medical history significant for hypothyroidism and recent pregnancy, presented to the hospital with complaints of right upper quadrant (RUQ) abdominal pain. She had gone out of the country in order to seek medical attention and was prescribed Flagyl and Ketorolac, with no symptomatic relief. She had worsening RUQ pain described as “colicky”, worse in the epigastric region, in addition to significant pruritus. Patient’s review of systems was positive for nausea, dark urine, and jaundice for the last 4 days. In the hospital, she had abnormal liver enzymes. Ultrasound and abdominal CT presented with significant biliary dilation. Magnetic resonance cholangiopancreatography (MRCP) demonstrated “innumerable gallstones”, measuring between 3 to 6mm, located in the cystic and common bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincteroctomy resolved patient symptomatology. (Figure) Discussion: Despite the increased frequency of gallstone disease in pregnancy, there is no consensus on the management of symptomatic cholelithiasis and/or choledocholithiasis, in this setting. Conservative management with symptomatic treatment has been the gold standard for decades. However, the risk for recurrent symptoms and subsequent hospital admission is high, at times up to 72%. The Society of American Gastrointestinal and Endoscopic Surgeons recommend laparoscopic cholecystectomy as the treatment of choice for symptomatic cholelithiasis, regardless of pregnancy state. Developing a standard guide to manage symptomatic cholelithiasis and choledocholithiasis in pregnancy would save both time and cost to the patient and healthcare system.Figure 1.: Shows the magnetic resonance cholangiopancreatography (MRCP) of our patient with numerous stones on the common bile duct Panel 1 and 2). Endoscopic retrograde cholangiopancreatography (ERCP) showing some of the multiple stones that came out after sphincterotomy was performed (Panel 3).

Prevalence of iron deficiency anaemia in patients of cholelithiasis undergoing laparoscopic cholecystectomy

Background: Gallstone disease (GSD) is a very common condition worldwide and the key event in the cholesterol stone formation is the supersaturation of bile with cholesterol. The role of trace elements like iron, calcium has been suggested in the pathogenesis of gallstones. Both iron deficiency and GSD are more prevalent in India. With this background, we studied the frequency of iron deficiency anaemia in GSD patients.Methods: This prospective observational study enrolled 150 adult patients undergoing laparoscopic cholecystectomy for symptomatic GSD in a north-Indian tertiary care hospital. Complete hemogram, serum ferritin, iron and unbound iron-binding capacity (TIBC) were performed in all patients. To simplify interpretation, anaemia was defined as Hb <12 gm/dl; iron deficiency was defined as either ferritin value lower than the reference range, or, if the ferritin was within the reference range, reduced % transferrin saturation with normal-or-high TIBC.Results: Anaemia was present in 66% and 77.3% were having iron deficiency; of which 84.5% were females. Iron deficiency with anaemia was present in 85.3%; therefore remaining patients had latent iron deficiency. Serum ferritin was normal or raised in 52 (68.1%) patients with iron deficiency, indicating that it is insensitive as a stand-alone test for iron deficiency.Conclusions: At a public health level, our results may suggest that addressing the problem of endemic iron deficiency may also reduce the possible development of GSD in the community. Thus, pre-operative assessment of iron status appears to be a cautious choice in all patients planned for cholecystectomy as indirectly it will address the problem of anaemia in the population.

Pathogenesis, Diagnosis and Treatment of Gallstone Disease A Brief Review

Gallstone disease is a gastrointestinal disease that results from the dysfunction of cholesterol, bile, and bilirubin metabolism. Gallstones in the gallbladder are common and form through cholelithiasis. They can also grow in biliary ducts through choledocholithiasis. In industrial countries, gallstone disease has increased in prevalence and affects up to 20% of the adult population. Its major risk factors are female gender, age, obesity, type 2 diabetes, rapid weight loss, physical inactivity, and genetic traits. Various systems for gallstone classification are available. Gallstones are classified as cholesterol, pigmented, and mixed gallstones in accordance with their chemical composition. Gallstone disease is either asymptomatic or has symptoms that manifest as pain in the right upper part of the abdomen, fever, and jaundice. The pathogenesis of this disease is related to the interaction between genetic and environmental factors, which include hepatic cholesterol hypersecretion, bile supersaturation, mucin, inflammatory changes, intestinal hypomotility, intestinal cholesterol hyperabsorption, and gut microbe alterations. The major genetic factors of this disease are the mutations in the hepatic cholesterol transporter ABCC8 and the cholecystokinin a receptor gene. Metabolic syndrome, insulin resistance, and type 2 diabetes increase the risk of developing gallstone disease. The standard diagnostic method for gallstone disease is ultrasound imaging. Medical treatment involves the administration of bile acid drugs and/or cholecystectomy.

From acute pancreatitis to pancreonecrosis during pregnancy

Acute pancreatitis during pregnancy is a rare but extremely formidable complication and accompanied by a high level of perinatal and maternal mortality. Excessive hypertriglyceridemia is an extremely important risk factor for pancreatitis, especially during pregnancy. The secretion of cholesterol in hepatic bile increases in the second trimester and reaches a peak in the third trimester compared with bile acids and phospholipids, which leads to a supersaturation of bile. This is determines the highest incidence of acute pancreatitis in pregnant women in the third trimester. Acute onset, nature of the disease and difficulties in diagnosis and treatment of acute pancreatitis in pregnant women significantly threaten the health of mother and fetus. Although most authors argue that treating acute pancreatitis during pregnancy is similar to treating non-pregnant patients, this is actually far from the truth. Pathogenesis features of acute pancreatitis in pregnant women come to the fore, which must be taken into account when managing these patients. Medical workers (primarily obstetricians) have a question about the advisability of preserving pregnancy, fetus, timing and method of abortion, and today these are extremely controversial decisions.Management of pregnant women with acute pancreatitis is an extremely difficult task, despite the achievements of recent years, and is accompanied by high perinatal and maternal mortality, the level of which depends on the severity of acute pancreatitis.The severe course of acute pancreatitis in pregnant women is extremely dangerous for the fetus and in all cases leads to its distress and in more than half of cases to fetal loss. The average severity of pancreatitis is also unfavorable for the fetus and is accompanied by its loss in every fourth case. Emergency abortion is indicated if triglycerides are the cause of acute pancreatitis. Management of such pregnant women requires a multidisciplinary approach to predict the course of pancreatitis, determine the tactics of pregnancy and acute pancreatitis, method and timing of delivery.

Gallstone formation analysis using the particle appearance, the particle binding to calcium ions, and the cholesterol nucleation with time in supersaturated taurocholate–lecithin–calcium ion solutions

AbstractWe conducted a time‐dependent study of cholesterol (Ch) nucleation to investigate the effect of calcium ions in the moderate supersaturated bile. In taurocholate/lecithin (TC/L) bile at a TC to L ratio of 5.1, the presence of calcium ions enhanced the nucleation rate of Ch. Contrarily, we observed the delayed nucleation of Ch after ~30 days in TC/L bile at a ratio of 2.0, regardless of the calcium ions. From the physical chemistry standpoint, the cholesterol activity (ChAT) is believed to be the driving force for Ch nucleation together with the sufficient nucleation sites. Hence, the micellar formation models along with the binding of TC monomers to calcium ions interpreted the time‐dependent results. Furthermore, a quasielastic light–scattering technique detected the formation of micelles and vesicles. In conclusion, the presence of calcium ions in TC/L bile at a high ratio enhances the vesicle appearance for nucleation sites and the high ChAT values for fast nucleation rate of Ch. However, an increase in the L concentration (i.e., low ratio bile) plays a significant role in the prevention of Ch gallstone formation, compared to the decrease in calcium ion concentration.

ACUTE PANCREATITIS AND PREGNANCY : A RARE AND SEVERE ASSOCIATION

Introduction Acute pancreatitis associated with pregnancy is a serious condition, surgical discovery or even necropsy and difficult diagnosis. We report a case of acute pancreatitis occurring in a pregnant woman. Observation This is a 29-year-old woman, nulliparous with no previous pathological history, presented to obstetric emergencies for hepatic colic. The patient had no transit disorder or gastrointestinal bleeding. Clinically, the patient was feverish, blood pressure was 16/9 mmHg and her hemodynamic status was stable. Obstetrical examination was normal, correlated with gestational age. The biological assessment performed showed anemia. The viral serology performed was negative. Liver status, renal status and coagulation status were normal. The diagnosis was acute pancreatitis and pre-eclampsia in pregnancy. Discussion Acute pancreatitis rarely occurs during pregnancy. It is associated with high maternal and fetal mortality. It occurs in most cases in the 3rd trimester of pregnancy [1]. In the 2nd and 3rd trimesters, supersaturation of bile in relation to increased cholesterol excretion and stagnation of supersaturated bile in the gallbladder induces formation of cholesterol crystals and gallstones [2]. In the 3rd trimester, the gravid uterus compresses the common bile duct and can lead to acute pancreatitis. Acute pancreatitis during pregnancy may be associated with pre-eclampsia that increases fetal mortality [3]. Conclusion Acute pancreatitis during pregnancy is a rare association, difficult to diagnose and has a terrible prognosis for both the mother and the fetus. The diagnostic and therapeutic delay will be fatal to the mother-child couple.

A Case Study on the management of Pittashmari w.s.r. to Gall Bladder Stone

Introduction: Ankylosing Spondylitis (AS) is a sero negative chronic inflammatory arthritis of Gall stone disease is a worldwide medical problem, but the incidence rates show substantial geographical variation, Cholelithiasis (gallstone formation) results from a combination of several factors, including super saturation of bile with cholesterol, accelerated nucleation of cholesterol monohydrate in bile, and bile stasis or delayed gallbladder emptying due to impaired gallbladder motility. In India it is more common in women in north, north-east and east as compared to other zones in the country. The disease Gall Stone has not been described directly in Ayurvedic classics. The word Ashmari in Ayurveda stands for stone which is described only in the context of Bastigata Ashmari (urinary calculi). After analyzing the Ayurvedic texts it was found that the bile secreted from gall bladder can be correlated with Accha Pitta mentioned in Ayurveda due to the similarity in location and function. The pathogenesis of the disease occurs due to the abnormal formation of Kapha during the process of digestion and its vitiation due to Vata. Once gallstones become symptomatic, definitive surgical intervention with cholecystectomy is usually indicated (typically, laparoscopic cholecystectomy is first-line therapy at centers with experience in this procedure). The present article deals with “Management of Pittashmari - A Case Study”

Genetics of gallstone disease.

Gallstone disease (GD) belongs to the most frequent disorders in gastroenterology and causes high costs in our health-care systems. Gallstones are uncommon in children but frequent in adults, in particular in women, and are triggered by exogenous risk factors. Here, we summarize the current knowledge concerning the contribution of inherited predisposition to gallstone risk. In this review, we present the current data and recent research on the genetics of gallstone disease. Several GD-predisposing gene variants have been reported, with most prominent effects being conferred by a common variant (p.D19H) of the hepatic and intestinal cholesterol transporter ABCG5/G8. A smaller group of patients might develop gallstones primarily due low phosphatidylcholine concentrations in bile as a result of loss-of-function mutations of the ABCB4 transporter (low phospholipid-associated cholelithiasis syndrome). Regardless of the origin, the risk factors for gallstones lead to the supersaturation of bile with insoluble compounds, in particular cholesterol. As result, cholesterol stones develop and present the most frequent type of gallstones. Laparoscopic cholecystectomy with low morbidity and mortality is currently the most common and effective method for the therapy of symptomatic gallbladder stones. Gallstone disease represents a multifactorial condition and previous studies have identified the major genetic contributors to gallstone formation. The increasing knowledge about the pathomechanisms of hepatobiliary metabolism and GD as well as the identification of additional risk factors might help to overcome the current invasive therapy by specific lifestyle intervention and precise molecular treatment.

Lack of a liver‐specific apolipoprotein (apo)A‐V in bile promotes cholesterol gallstone formation by disrupting biliary cholesterol homeostasis in mice

BackgroundApoA‐V is synthesized exclusively by the liver and secreted into the circulation, involving in plasma lipoprotein and lipid metabolism. Although its concentration in human plasma is extremely low (114–258 ng/mL), 1,000 to 10,000‐fold lower than that of apoB‐100 and apoA‐I, respectively, human and mice lacking functional apoA‐V suffer from hypertriglyceridemia. Because our new results found that apoA‐V is also secreted into bile, we hypothesize that it plays an important role in regulating biliary cholesterol metabolism, and its deficiency reduces cholesterol solubility in bile, promoting cholesterol crystallization and gallstone formation.MethodsTo explore the lithogenic mechanisms of biliary apoA‐V deficiency, male apoA‐V knockout (KO) and wild‐type (WT) mice (n=10 per group) were fed a lithogenic diet for 4 wk. Gallstones and cholesterol crystallization in bile were examined by physical‐chemical methods. Hepatic lipid output was determined by biliary secretion studies. Gene expression and protein content were analyzed by qRT‐PCR, Western blots, and ELISA.ResultsCompared to the chow diet, feeding the lithogenic diet significantly (P<0.01) reduced hepatic apoA‐V mRNA and protein levels by 55% and its bile concentrations from 45.7±12.4 ng/mL to 16.7±6.0 ng/mL in WT mice. ApoA‐V was associated only with vesicles, but not micelles, in bile of WT mice. Biliary cholesterol, but not phospholipid or bile salt, output was higher (P<0.05) in KO mice (29.0±8.5 μmol/h/kg) than in WT mice (20.4±5.5 μmol/h/kg), leading to cholesterol‐supersaturated bile. The deficiency of apoA‐V in bile reduced biliary cholesterol solubility and promoted cholesterol crystallization through the liquid crystalline pathway by enhancing biliary unilamellar vesicle aggregation and fusion to form unstable multilamellar vesicles in KO mice. After 50 ng/mL of apoA‐V protein isolated from WT mice was added to supersaturated model bile, cholesterol crystallization was significantly delayed than that added the protein at 0 ng/mL. This implies that apoA‐V plays a key role in regulating cholesterol solubility in bile by modulating the physical state of cholesterol carriers. In addition, the lack of apoA‐V impaired gallbladder emptying and refilling function, thus promoting the accumulation of excess mucin gel and the formation of biliary sludge, a precursor of gallstones. These abnormalities enhanced the growth and agglomeration of solid cholesterol crystal into microlithiasis. After 4 wk of feeding, gallstone prevalence was higher (P<0.05) in KO mice (60%) than in WT mice (25%).ConclusionsThese findings clearly demonstrate that the liver‐specific protein apoA‐V plays a critical role in the regulation of biliary cholesterol metabolism and transport, and its lack in bile dramatically enhances cholelithogenesis by disrupting biliary cholesterol homeostasis. Increasing biliary apoA‐V may be a novel and efficient approach for the prevention of cholesterol gallstones.Support or Funding InformationThis work was supported in part by research grants DK101793, DK106249 and AA03557, all from the National Institutes of Health (US Public Health Service).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Correlation of gallstone disease with iron deficiency anemia

Association between gallstone disease and iron deficiency anemia is not uncommon. The objective of this study was to assess correlation between gallstone formation and iron deficiency anemia in patients presenting with gallstone disease. Materials and Methods: A total of 60 patients' sonological evidence of gallstone were included in the study. Serum ferritin and serum iron levels were estimated. Gallstone patients were divided into anemic and non-anemic groups and compared with each other. Data were analyzed with descriptive statistical principles. Patients and Methods: Chi-square test or Fisher's exact test , Yates correction, independent t-test or Mann–Whitney U test. Results: There was significant association between serum iron and hemoglobin levels in patients with gallstone disease. This study suggests that iron deficiency leading to anemia plays a significant role in super saturation of bile, leading to stone formation in the gall bladder. Conclusions: Low serum iron and ferritin levels were found to be statistically significant in gallstone patients. Significant correlation found between iron deficiency and gallstone disease. Iron deficiency and low serum ferritin are probably independent risk factors operating for the causation of gallstones.

Biliary Polyunsaturated Fatty Acids and Telocytes in Gallstone Disease

It has been reported that intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risk of coronary heart disease. It also influences bile composition, decreasing biliary cholesterol saturation in the bile of patients with gallstones. In addition to bile composition disturbances, gallbladder hypomotility must be a cofactor in the pathogenesis of cholelithiasis, as it leads to the prolonged nucleation phase. Our current knowledge about gallbladder motility has been enhanced by the study of a population of newly described interstitial (stromal) cells—telocytes (TCs). The purpose of this study was to determine whether TC loss, reported by our team recently, might be related to bile lithogenicity, expressed as cholesterol saturation index or the difference in biliary PUFA profiles in patients who suffer from cholecystolithiasis and those not affected by this disease. We determined biliary lipid composition including the fatty acid composition of the phospholipid species in bile. Thus, we investigated whether differences in biliary fatty acid profiles (ω-3 PUFA and ω-6 PUFA) in gallbladder bile may influence its lithogenicity and the quantity of TCs within the gallbladder wall. We conclude that the altered PUFA concentrations in the gallbladder bile, with elevation of ω-6 PUFA, constitute important factors influencing TC density in the gallbladder wall, being one of the possible pathophysiological components for the gallstone disease development. This study established that altered bile composition in patients with cholelithiasis may influence TC quantity within the gallbladder muscle, and we concluded that reduction in TC number may be a consequence of the supersaturated bile toxicity, while some other bile components (ω-3 PUFA, glycocholic, and taurocholic acids) may exert protective effects on TC and thus possibly influence the mechanisms regulating gallbladder and extrahepatic bile duct motility. Thus, ω-3 PUFA may represent a possible option to prevent formation of cholesterol gallstones.

The Concept of Cholelithiasis as Per Ayurvedic Text

Cholelithiasis (gallstone formation) results from a combination of several factors, including super saturation of bile with cholesterol, accelerated nucleation of cholesterol monohydrate in bile, and bile stasis or delayed gallbladder emptying due to impaired gallbladder motility. In India it is more common in women in north, north-east and east as compared to other zones in the country. The disease Gall Stone has not been described directly in Ayurvedic classics. The word Ashmari in Ayurveda stands for stone which is described only in the context of Bastigat Ashmari (urinary calculi). After analyzing the Ayurvedic texts it was found that the bile secreted from gall bladder can be correlated with Accha Pitta mentioned in Ayurveda due to the similarity in location and function. The pathogenesis of the disease occurs due to the abnormal formation of Kapha during the process of digestion and its vitiation due to Vata. The present article deals with description of formation of gall stone from the Ayurvedic perspective. Along with this the specific remedy for gall stone according to Ayurveda is also described.

Prevention of gallbladder hypomotility via FATP2 inhibition protects from lithogenic diet-induced cholelithiasis.

Gallstone disease is a widespread disorder costing billions for annual treatment in the United States. The primary mechanisms underlying gallstone formation are biliary cholesterol supersaturation and gallbladder hypomotility. The relative contribution of these two processes has been difficult to dissect, as experimental lithogenic diets cause both bile supersaturation and alterations in gallbladder motility. Importantly, there is no mechanistic explanation for obesity as a major risk factor for cholelithiasis. We discovered that lithogenic diets induce ectopic triacylglycerol (TAG) accumulation, a major feature of obesity and a known muscle contraction impairing condition. We hypothesized that prevention of TAG accumulation in gallbladder walls may prevent gallbladder contractile dysfunction without impacting biliary cholesterol saturation. We utilized adeno-associated virus-mediated knock down of the long-chain fatty acid transporter 2 (FATP2; Slc27A2), which is highly expressed by gallbladder epithelial cells, to downregulate lithogenic diet-associated TAG accumulation. FATP2-knockdown significantly reduced gallbladder TAG, but did not affect key bile composition parameters. Importantly, measurements with force displacement transducers showed that contractile strength in FATP2-knockdown gallbladders was significantly greater than in control gallbladders following lithogenic diet administration, and the magnitude of this effect was sufficient to prevent the formation of gallstones. FATP2-driven fatty acid uptake and the subsequent TAG accumulation in gallbladder tissue plays a pivotal role in cholelithiasis, and prevention of this process can protect from gallstone formation, even in the context of supersaturated bile cholesterol levels, thus pointing to new treatment approaches and targets.