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1
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Portincasa P, Bonfrate L, Wang DQH, Frühbeck G, Garruti G, Di Ciaula A. Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract. Eur J Clin Invest 2022; 52:e13846. [PMID: 35904418 DOI: 10.1111/eci.13846] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 11/09/2022]
Abstract
Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - David Q-H Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, Pamplona, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Gabriella Garruti
- Department of Emergency and Organ Transplants, Unit of Endocrinology, University of Bari Medical School, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
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Differences and Similarities in Neuropathy in Type 1 and 2 Diabetes: A Systematic Review. J Pers Med 2021; 11:jpm11030230. [PMID: 33810048 PMCID: PMC8004786 DOI: 10.3390/jpm11030230] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/10/2021] [Accepted: 03/18/2021] [Indexed: 12/11/2022] Open
Abstract
Background: Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes mellitus. Its presence is associated with increased morbidity and mortality. Although several studies have found alterations at somatic motor, sensory levels and at the level of autonomic nervous system in diabetic patients, there is not a systematic approach regarding the differences in neuropathy between the major variants of diabetes, e.g., type 1 and 2 diabetes at both neurological and molecular level. Data sources: we systematically (Medline, Scopus, and Cochrane databases) evaluated the literature related to the difference of neuropathy in type 1 and 2 diabetes, differences in molecular biomarkers. Study characteristics: seventeen articles were selected based on pre-defined eligibility criteria. Conclusions: both superficial sensitivity (primarily thermal sensitivity to cold) and deep sensitivity (such as vibratory sensitivity), have been reported mainly in type 2 diabetes. Cardiac autonomic neuropathy is one of the diabetic complications with the greatest impact at a clinical level but is nevertheless one of the most underdiagnosed. While for type 1 diabetes patients most neuropathy alterations have been reported for the Valsalva maneuver and for the lying-to-standing test, for type 2 diabetes patients, alterations have been reported for deep-breathing test and the Valsalva test. In addition, there is a greater sympathetic than parasympathetic impairment, as indicated by the screening tests for autonomic cardiac neuropathy. Regarding subclinical inflammation markers, patients with type 2 diabetes showed higher blood levels of inflammatory markers such as high-sensitivity C-reactive protein, proinflammatory cytokines IL-6, IL-18, soluble cell adhesion molecules and E-selectin and ICAM-1, than in type 1 diabetes patients. By contrast, the blood levels of adiponectin, an adipocyte-derived protein with multiple paracrine and endocrine activities (anti-inflammatory, insulin-sensitizing and proangiogenic effects) are higher in type 1 than in type 2 diabetic patients. This review provides new insights into the clinical differences in type 1 and 2 diabetes and provide future directions in this research field.
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Rahmani B, Gandhi J, Joshi G, Smith NL, Reid I, Khan SA. The Role of Diabetes Mellitus in Diseases of the Gallbladder and Biliary Tract. Curr Diabetes Rev 2020; 16:931-948. [PMID: 32133965 DOI: 10.2174/1573399816666200305094727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 02/18/2020] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The increasing prevalence of diabetes mellitus worldwide continues to pose a heavy burden. Though its gastrointestinal impact is appropriately recognized, the lesser known associations may be overlooked. OBJECTIVE We aim to review the negative implications of diabetes on the gallbladder and the biliary tract. METHODS A MEDLINE® database search of literature was conducted with emphasis on the previous five years, combining keywords such as "diabetes," "gallbladder," and "biliary". RESULTS The association of diabetes to the formation of gallstones, gallbladder cancer, and cancer of the biliary tract are discussed along with diagnosis and treatment. CONCLUSION Though we uncover the role of diabetic neuropathy in gallbladder and biliary complications, the specific individual diabetic risk factors behind these developments is unclear. Also, in addition to diabetes control and surgical gallbladder management, the treatment approach also requires further focus.
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Affiliation(s)
- Benjamin Rahmani
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Jason Gandhi
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Medical Student Research Institute, St. George’s University School of Medicine, Grenada, West Indies
| | - Gunjan Joshi
- Department of Internal Medicine, Stony Brook Southampton Hospital, Southampton, NY, USA
| | | | - Inefta Reid
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Sardar Ali Khan
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Department of Urology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
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Di Ciaula A, Molina-Molina E, Bonfrate L, Wang DQH, Dumitrascu DL, Portincasa P. Gastrointestinal defects in gallstone and cholecystectomized patients. Eur J Clin Invest 2019; 49:e13066. [PMID: 30592298 PMCID: PMC8118136 DOI: 10.1111/eci.13066] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 12/25/2018] [Accepted: 12/27/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy. MATERIALS AND METHODS Forty-six gallstone patients (age 55 ± 2 years; 15M, 31F) and 24 cholecystectomized patients (age 57 ± 2 years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51 ± 2 years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose-enriched standard liquid meal. RESULTS Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls. CONCLUSION Gallstone patients with the gallbladder "in situ" or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens.
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Affiliation(s)
- Agostino Di Ciaula
- Division of Internal Medicine, Hospital of Bisceglie, ASL BAT, Bisceglie, Italy
| | - Emilio Molina-Molina
- Department of Biomedical Sciences and Human Oncology, Clinica Medica “A. Murri”, University of Bari Medical School, Bari, Italy
| | - Leonilde Bonfrate
- Department of Biomedical Sciences and Human Oncology, Clinica Medica “A. Murri”, University of Bari Medical School, Bari, Italy
- Division of Geriatrics and Gerontology, Hospital “Miulli”, Acquaviva delle Fonti, Italy
| | - David Q.-H. Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York
| | - Dan L. Dumitrascu
- 2nd Department of Internal Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica “A. Murri”, University of Bari Medical School, Bari, Italy
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Di Ciaula A, Wang DQH, Portincasa P. Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention. Expert Rev Gastroenterol Hepatol 2019; 13:157-171. [PMID: 30791781 DOI: 10.1080/17474124.2019.1549988] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 11/15/2018] [Indexed: 02/07/2023]
Abstract
Cholesterol gallstone disease have relationships with various conditions linked with insulin resistance, but also with heart disease, atherosclerosis, and cancer. These associations derive from mechanisms active at a local (i.e. gallbladder, bile) and a systemic level and are involved in inflammation, hormones, nuclear receptors, signaling molecules, epigenetic modulation of gene expression, and gut microbiota. Despite advanced knowledge of these pathways, the available therapeutic options for symptomatic gallstone patients remain limited. Therapy includes oral litholysis by the bile acid ursodeoxycholic acid (UDCA) in a small subgroup of patients at high risk of postdissolution recurrence, or laparoscopic cholecystectomy, which is the therapeutic radical gold standard treatment. Cholecystectomy, however, may not be a neutral event, and potentially generates health problems, including the metabolic syndrome. Areas covered: Several studies on risk factors and pathogenesis of cholesterol gallstone disease, acting at a systemic level have been reviewed through a PubMed search. Authors have focused on primary prevention and novel potential therapeutic strategies. Expert commentary: The ultimate goal appears to target the manageable systemic mechanisms responsible for gallstone occurrence, pointing to primary prevention measures. Changes must target lifestyles, as well as experimenting innovative pharmacological tools in subgroups of patients at high risk of developing gallstones.
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Affiliation(s)
- Agostino Di Ciaula
- a Division of Internal Medicine , Hospital of Bisceglie , Bisceglie , Italy
| | - David Q-H Wang
- b Department of Medicine, Division of Gastroenterology and Liver Diseases , Marion Bessin Liver Research Center, Albert Einstein College of Medicine , Bronx , NY , USA
| | - Piero Portincasa
- c Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri" , University of Bari Medical School , Bari , Italy
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Abstract
PURPOSE OF REVIEW Gallstone disease is a major epidemiologic and economic burden worldwide, and the most frequent form is cholesterol gallstone disease. RECENT FINDINGS Major pathogenetic factors for cholesterol gallstones include a genetic background, hepatic hypersecretion of cholesterol, and supersaturated bile which give life to precipitating cholesterol crystals that accumulate and grow in a sluggish gallbladder. Additional factors include mucin and inflammatory changes in the gallbladder, slow intestinal motility, increased intestinal absorption of cholesterol, and altered gut microbiota. Mechanisms of disease are linked with insulin resistance, obesity, the metabolic syndrome, and type 2 diabetes. The role of nuclear receptors, signaling pathways, gut microbiota, and epigenome are being actively investigated. SUMMARY Ongoing research on cholesterol gallstone disease is intensively investigating several pathogenic mechanisms, associated metabolic disorders, new therapeutic approaches, and novel strategies for primary prevention, including lifestyles.
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Affiliation(s)
| | - David Q.-H. Wang
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica “A. Murri”, University of Bari Medical School, Bari, Italy
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Arshad F, Laway BA, Rather TA, Kuchay MS, Khan SH. Impaired gallbladder motility in adults with newly detected type 2 diabetes and lack of reversibility after achieving euglycemia. Can J Diabetes 2014; 39:101-4. [PMID: 25444680 DOI: 10.1016/j.jcjd.2014.07.223] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 07/31/2014] [Accepted: 07/31/2014] [Indexed: 11/30/2022]
Abstract
OBJECTIVE The effects of hyperglycemia and normoglycemia on gallbladder emptying have not been studied in detail. This prospective case-control study was designed to investigate the gallbladder ejection fraction in patients with newly detected diabetes and to assess the impact of restoring normoglycemia on gallbladder ejection fraction in such patients. METHODS (99m)Tc-mebrofenin scintigraphy was performed in 22 patients with newly detected type 2 diabetes for measurement of gallbladder ejection fraction. The scintigraphy was performed at the time of first presentation and again 6 months after control of diabetes (glycated hemoglobin [A1C] <7%). Also, gallbladder ejection fraction was measured in 20 age- and sex-matched controls without diabetes. RESULTS Gallbladder ejection fraction was lower in patients with newly detected diabetes compared with controls (31.4%±5.9% vs. 70.7%±4.3%, p<0.001). Gallbladder ejection fraction did not improve after the treatment of diabetes mellitus (21.3%±5.7%, p=0.395). CONCLUSIONS Gallbladder ejection fraction was markedly reduced in patients with newly detected diabetes compared to controls without diabetes. Control of diabetes and normalization of A1C did not reverse the motility defect.
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Affiliation(s)
- Faheem Arshad
- Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India
| | - Bashir Ahmad Laway
- Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
| | - Tanveer Ahmad Rather
- Department of Nuclear Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India
| | - Mohammad Shafi Kuchay
- Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India
| | - Shoukat Hussain Khan
- Department of Nuclear Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India
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Bonfrate L, Wang DQH, Garruti G, Portincasa P. Obesity and the risk and prognosis of gallstone disease and pancreatitis. Best Pract Res Clin Gastroenterol 2014; 28:623-635. [PMID: 25194180 DOI: 10.1016/j.bpg.2014.07.013] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 07/02/2014] [Accepted: 07/15/2014] [Indexed: 02/06/2023]
Abstract
Obesity is a risk factor for the formation of cholesterol gallstones and exposes patients to increased risk of gallstone-related complications and cholecystectomy. Rapid weight loss achieved by very low calorie diets or bariatric surgery is also a risk factor for cholelithiasis in obese patients, and therapy should take into account the higher prevalence of gallstones, the possibility of more frequent complications and the need for prophylactic treatment with oral ursodeoxycholic acid during weight loss. Obesity is also frequent in children and adolescents, and the burden of cholesterol cholelithiasis is increasing in this population. The chance to develop acute pancreatitis and the severity of the disease are higher in obese subjects because of specific pathogenic factors, including supersaturated bile and crystal formation, rapid weight loss, and visceral obesity. All health policies aimed at reducing the incidence of obesity worldwide will decrease the incidence of gallstones and gallstone-related complications. The pathophysiological scenarios and the therapeutic implications for obesity, gallstone disease, and pancreatitis are discussed.
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Affiliation(s)
- Leonilde Bonfrate
- Residency Programme in Internal Medicine, University of Bari Medical School, 70124 Bari, Italy.
| | - David Q-H Wang
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
| | - Gabriella Garruti
- Department of Emergency and Organ Transplants, Section of Endocrinology, Andrology and Metabolic Diseases, University of Bari Medical School, 70124 Bari, Italy.
| | - Piero Portincasa
- Department of Biomedical Sciences and Human Oncology, Clinica Medica "A. Murri", University of Bari Medical School, Piazza Giulio Cesare 11, 70124 Bari, Italy.
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Said K, Edsborg N, Albiin N, Bergquist A. Gallbladder emptying in patients with primary sclerosing cholangitis. World J Gastroenterol 2009; 15:3498-503. [PMID: 19630104 PMCID: PMC2715975 DOI: 10.3748/wjg.15.3498] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess gallbladder emptying and its association with cholecystitis and abdominal pain in patients with primary sclerosing cholangitis (PSC).
METHODS: Twenty patients with PSC and ten healthy subjects were investigated. Gallbladder fasting volume, ejection fraction and residual volume after ingestion of a test meal were compared in patients with PSC and healthy controls using magnetic resonance imaging. Symptoms, thickness and contrast enhancement of the gallbladder wall and the presence of cystic duct strictures were also assessed.
RESULTS: Median fasting gallbladder volume in patients with PSC [67 (19-348) mL] was twice that in healthy controls [32 (16-55) mL] (P < 0.05). The median postprandial gallbladder volume in patients with PSC was significantly larger than that in healthy controls (P < 0.05). There was no difference in ejection fraction, gallbladder emptying volume or mean thickness of the gallbladder wall between PSC patients and controls. Contrast enhancement of the gallbladder wall in PSC patients was higher than that in controls; (69% ± 32%) and (42% ± 21%) (P < 0.05). No significant association was found between the gallbladder volumes and occurrence of abdominal pain in patients and controls.
CONCLUSION: Patients with PSC have increased fasting gallbladder volume. Gallbladder Mucosal dysfunction secondary to chronic cholecystitis, may be a possible mechanism for increased gallbladder.
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Portincasa P, Di Ciaula A, Wang HH, Palasciano G, van Erpecum KJ, Moschetta A, Wang DQH. Coordinate regulation of gallbladder motor function in the gut-liver axis. Hepatology 2008; 47:2112-2126. [PMID: 18506897 DOI: 10.1002/hep.22204] [Citation(s) in RCA: 101] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Gallstones are one of the most common digestive diseases with an estimated prevalence of 10%-15% in adults living in the western world, where cholesterol-enriched gallstones represent 75%-80% of all gallstones. In cholesterol gallstone disease, the gallbladder becomes the target organ of a complex metabolic disease. Indeed, a fine coordinated hepatobiliary and gastrointestinal function, including gallbladder motility in the fasting and postprandial state, is of crucial importance to prevent crystallization and precipitation of excess cholesterol in gallbladder bile. Also, gallbladder itself plays a physiopathological role in biliary lipid absorption. Here, we present a comprehensive view on the regulation of gallbladder motor function by focusing on recent discoveries in animal and human studies, and we discuss the role of the gallbladder in the pathogenesis of gallstone formation.
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Affiliation(s)
- Piero Portincasa
- Department of Internal Medicine and Public Medicine, Clinica Medica A. Murri, University of Bari Medical School, Bari, Italy.
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Swartz-Basile DA, Goldblatt MI, Ho Choi S, Svatek C, Tran K, Nakeeb A, Pitt HA. Biliary lipids and cholesterol crystal formation in leptin-deficient obese mice. HPB (Oxford) 2006; 8:386-92. [PMID: 18333092 PMCID: PMC2020751 DOI: 10.1080/13651820600641233] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Obesity is often associated with increased biliary cholesterol secretion resulting in cholesterol gallstone formation. We have previously demonstrated that leptin-deficient C57Bl/6J Lep ob obese mice have abnormal biliary motility and are prone to cholesterol crystal formation. In addition, others have demonstrated that leptin-deficient mice when fed a lithogenic diet for eight weeks are not prone to gallstone formation. However, the biliary lipid and in vivo cholesterol crystal response of homozygous and heterozygous leptin-deficient mice to four weeks on a lithogenic diet has not been studied. Therefore, we tested the hypothesis that lithogenic diets influence gallbladder bile composition, serum lipids and cholesterol crystal formation in homozygous and heterozygous leptin-deficient mice compared to normal lean controls. METHODS 319 female lean control mice, 280 heterozygous lep ob obese mice and 117 homozygous lep ob obese mice were studied. Mice were fed either a lithogenic or control non-lithogenic chow diet for four weeks. Gallbladder volumes were measured, and bile was pooled to calculate cholesterol saturation indices. Serum cholesterol, glucose, and leptin levels were determined. Hepatic fat vacuoles were counted, and bile was observed microscopically for cholesterol crystal formation. RESULTS The lithogenic diet and mouse strain influenced body and liver weights, gallbladder volume, cholesterol crystal formation, serum cholesterol, glucose and leptin levels and hepatic fat vacuole numbers. However, only diet, not strain, altered biliary cholesterol saturation. CONCLUSION The association among obesity, leptin, and gallstone formation may be primarily related to altered gallbladder motility and cholesterol crystal formation and only secondarily to biliary cholesterol saturation.
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Affiliation(s)
| | | | | | - Carol Svatek
- Department of Surgery, Medical College of Wisconsin
| | - Khoi Tran
- Department of Surgery, Medical College of Wisconsin
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Portincasa P, Moschetta A, Petruzzelli M, Palasciano G, Di Ciaula A, Pezzolla A. Gallstone disease: Symptoms and diagnosis of gallbladder stones. Best Pract Res Clin Gastroenterol 2006; 20:1017-1029. [PMID: 17127185 DOI: 10.1016/j.bpg.2006.05.005] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The clinical aspects and the diagnostic features of gallstone disease are described. The natural history of silent gallstones is overviewed, and the risk of developing symptoms and complications is also discussed. The importance of colicky pain as a specific gallstone symptom is highlighted, and the role of both laboratory tests and diagnostic investigations for differential diagnosis is discussed. Finally, we describe the diagnostic features of gallbladder stone disease, including indications, sensitivity, specificity, and limitations of different test investigations under special circumstances.
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Affiliation(s)
- P Portincasa
- Clinica Medica A. Murri, Department of Internal and Public Medicine, University of Bari Medical School, Piazza Giulio Cesare 11-Policlinico-70124 Bari, Italy.
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Szepes A, Bertalan V, Várkonyi T, Pávics L, Lonovics J, Madácsy L. Diagnosis of gallbladder dyskinesia by quantitative hepatobiliary scintigraphy. Clin Nucl Med 2005; 30:302-7. [PMID: 15827396 DOI: 10.1097/01.rlu.0000159522.19509.30] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM The aim of the present study was to develop a new pharmacologic method during hepatobiliary scintigraphy by which patients with functional and organic forms of gallbladder (GB) dysfunction can be differentiated. METHODS Quantitative hepatobiliary scintigraphy (QHBS) was performed on 31 patients with impaired GB motility selected by cerulein-augmented ultrasonography. Nineteen patients had acalculous biliary pain (ABP) and suspected GB dyskinesia, 6 patients had celiac disease, and 6 patients had type II diabetes mellitus. Sixty minutes after the isotope administration, 1 ng/bwkg/min cerulein (CCK10) was infused for 10 minutes, and then from the 90th minute, an equivalent dose of CCK10 was infused in the presence of 0.5 mg sublingual glyceryl trinitrate (GTN) in 12 or placebo in 7 consecutive patients. The GB ejection fraction (GBEF) was calculated repeatedly in time periods from 60 to 90 and from 90 to 120 minutes. RESULTS In the majority of patients with ABP and suspected GB dyskinesia, CCK10 and GTN coadministration normalized the previously impaired GB-emptying. When the cumulative results of all 12 patients were calculated, we demonstrated significant differences (P=0.003) in the GBEF between the first (CCK10) versus the second (CCK10 plus GTN) stimuli: 19+/-11% versus 40+/-17%, respectively. In contrast, in 12 patients with celiac sprue and diabetes mellitus, no differences in the GBEF were detected when the first (CCK10 alone) versus the second (CCK10 plus GTN) stimuli was compared: 21+/-10% versus 22+/-13%, respectively. Finally, placebo and CCK10 coadministration in 7 consecutive patients with ABP and suspected GB dyskinesia did not influence the GBEF as compared with CCK10 alone: 13+/-9% versus 15+/-10%, respectively. CONCLUSION GTN and CCK10 coadministration induces a significant improvement of the GBEF in patients with GB dyskinesia. The application of this new pharmacologic test during QHBS permitted the noninvasive separation of those patients with secondary impaired GB-emptying as a result of GB dyskinesia from those with primary forms of GB hypokinesia.
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Affiliation(s)
- Attila Szepes
- 1st Department of Internal Medicine, University of Szeged, Szeged, Hungary.
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14
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Portincasa P, Moschetta A, Berardino M, Di-Ciaula A, Vacca M, Baldassarre G, Pietrapertosa A, Cammarota R, Tannoia N, Palasciano G. Impaired gallbladder motility and delayed orocecal transit contribute to pigment gallstone and biliary sludge formation in beta-thalassemia major adults. World J Gastroenterol 2004; 10:2383-2390. [PMID: 15285024 PMCID: PMC4576293 DOI: 10.3748/wjg.v10.i16.2383] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2004] [Revised: 02/14/2004] [Accepted: 03/13/2004] [Indexed: 12/15/2022] Open
Abstract
AIM Gallbladder and gastrointestinal motility defects exist in gallstones patients and to a lesser extent in pigment gallstone patients. To investigated the role of gallbladder and gastrointestinal motility disorders in pigment gallstone formation in beta-thalassemia major. METHODS Twenty-three patients with beta-thalassemia major (16 females; age range 18-37 years) and 70 controls (47 females, age range 18-40 years) were studied for gallbladder and gastric emptying (functional ultrasonography), orocecal transit (OCTT, H(2)-breath test), autonomic dysfunction (sweat-spot, cardiorespiratory reflex tests), bowel habits, gastrointestinal symptoms and quality of life (all with questionnaires). Gallbladder content (ultrasonography) was examined before and during 8-12 mo follow-up. RESULTS Gallstones and/or biliary sludge were found in 13 (56%) patients. beta-thalassemia major patients had increased fasting (38.0+/-4.8 mL vs 20.3+/-0.7 mL, P = 0.0001) and residual (7.9+/-1.3 mL vs 5.1+/-0.3 mL, P = 0.002) volume and slightly slower emptying (24.9+/-1.7 min vs 20.1+/-0.7 min, P = 0.04) of the gallbladder, together with longer OCTT (132.2+/-7.8 min vs 99.7+/-2.3 min, P = 0.00003) than controls. No differences in gastric emptying and bowel habits were found. Also, patients had higher dyspepsia (score: 6.7+/-1.2 vs 4.9+/-0.2, P = 0.027), greater appetite (P = 0.000004) and lower health perception (P = 0.00002) than controls. Autonomic dysfunction was diagnosed in 52% of patients (positive tests: 76.2% and 66.7% for parasympathetic and sympathetic involvement, respectively). Patients developing sludge during follow-up (38%, 2 with prior stones) had increased fasting and residual gallbladder volume. CONCLUSION Adult beta-thalassemia major patients have gallbladder dysmotility associated with delayed small intestinal transit and autonomic dysfunction. These abnormalities apparently contribute together with haemolytic hyperbilirubinemia to the pathogenesis of pigment gallstones/sludge in beta-thalassemia major.
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Affiliation(s)
- Piero Portincasa
- Section of Internal Medicine, Department of Internal and Public Medicine, University Medical School of Bari, P.zza G. Cesare 11, 70124 Bari, Italy.
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15
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Portincasa P, Moschetta A, Colecchia A, Festi D, Palasciano G. Measurements of gallbladder motor function by ultrasonography: towards standardization. Dig Liver Dis 2003; 35 Suppl 3:S56-S61. [PMID: 12974512 DOI: 10.1016/s1590-8658(03)00096-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
As real-time ultrasonography is a cheap, noninvasive, relatively easy, validated and reproducible technique, it can be repeated over time to document time-related changes of gallbladder motor function. Ultimately, functional ultrasonography estimates gallbladder shape and volume in fasting state and in response to a test meal (liquid or mixed solid-liquid, provided there is sufficient fat content) or exogenous stimulus (e.g., i.v. cholecystokinin or ceruletide). Although functional ultrasonography of the gallbladder has been mainly used for research purposes in specific referral centres, its simplicity makes such a technique appealing in the clinical setting to assess gallbladder motor function in both health and disease. Indications include the study of healthy subjects and of patients during pathophysiologically relevant conditions; in particular when subjects are at risk for gallbladder stasis and gallstone disease or during gallstone disease when a decision concerning medical dissolution therapy is required.
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Affiliation(s)
- P Portincasa
- Section of Internal Medicine, Department of Internal Medicine and Public Medicine, University Medical School of Bari, Piazza G. Cesare, 70124 Bari, Italy.
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16
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Fraquelli M, Pagliarulo M, Colucci A, Paggi S, Conte D. Gallbladder motility in obesity, diabetes mellitus and coeliac disease. Dig Liver Dis 2003; 35 Suppl 3:S12-S16. [PMID: 12974503 DOI: 10.1016/s1590-8658(03)00087-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
We reviewed data on gallbladder motility in obesity, diabetes and coeliac disease. In obesity, a condition characterised by increased risk of gallstone(s), decreased gallbladder motility has heterogeneously been reported as a consequence of the different type of meals used to induce gallbladder contraction, characteristics of the population studied, technique used, and proportion of patients with hyperinsulinaemia. Moreover, recent studies have evaluated the effect of dietary restriction on gallbladder motility in obese patients. A two- to three-fold increase in the risk of cholesterol gallstone(s) has been reported in diabetic patients, mainly in relation to obesity and hypertriglyceridaemia. Furthermore, decreased gallbladder motility has been described and attributed to other factors, including underlying autonomic neuropathy, reduced gallbladder sensitivity to cholecystokinin and/or reduced number of cholecystokinin receptors on the gallbladder wall. Impaired gallbladder motility has been reported also in patients with coeliac disease in relation to reduced secretion of enteric hormones and/or decreased gallbladder sensitivity to them. In particular, untreated coeliacs, when compared to controls, showed low postprandial cholecystokinin and increased fasting somatostatin levels. Interestingly, the correlation between fasting somatostatin levels and gallbladder size has clearly been confirmed in patients affected by somatostatinoma or treated with somatostatin or its analogues. Gallbladder motility can be affected by various clinical conditions, such as obesity, diabetes mellitus and coeliac disease.
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Várkonyi TT, Lengyel C, Madácsy L, Velösy B, Kempler P, Fazekas T, Pávics L, Csernay L, Lonovics J. Gallbladder hypomotility in diabetic polyneuropathy. Clin Auton Res 2001; 11:377-81. [PMID: 11794719 DOI: 10.1007/bf02292770] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This study was performed to evaluate the gallbladder motility in long-standing diabetes mellitus. The gallbladder function of diabetic patients was measured by means of quantitative hepatobiliary scintigraphy, and the severity of the associated autonomic and sensory polyneuropathy was determined. The presence of a marked gallbladder hypomotility was established, and a positive correlation was observed between the severity of the autonomic disturbance and the contractile disorder. This study underlines the important role of the neuropathy in the development of gallbladder hypomotility accompanying long-term diabetes mellitus.
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Affiliation(s)
- T T Várkonyi
- 1st Department of Medicine, University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Medical and Pharmaceutical Center Szeged, Hungary.
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18
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Dhiman RK, Arke L, Bhansali A, Gupta S, Chawla YK. Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus. J Gastroenterol Hepatol 2001; 16:1044-50. [PMID: 11595071 DOI: 10.1046/j.1440-1746.2001.02586.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). METHODS Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. RESULTS Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3 +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0 vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs 20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/- 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/- 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. CONCLUSION Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.
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Affiliation(s)
- R K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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19
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Pazzi P, Scagliarini R, Gamberini S, Pezzoli A. Review article: gall-bladder motor function in diabetes mellitus. Aliment Pharmacol Ther 2000; 14 Suppl 2:62-5. [PMID: 10903007 DOI: 10.1046/j.1365-2036.2000.014s2062.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
Although some controversy exists, diabetic patients generally are thought to have a two- to threefold increased risk of cholesterol gallstones. From previous studies there is no convincing evidence for a supersaturated bile in diabetics, whereas several reports indicate that impaired gall-bladder emptying could be one of the important factors in the increased incidence of gallstones in diabetics. However, studies of gall-bladder motility in diabetics have yielded conflicting results, probably because of substantial heterogeneity in the patients studied, emptying stimulus and technique used to assess gall-bladder motor function. The mechanism of the gall-bladder emptying abnormality in diabetics is not completely understood, although it has been proposed that it could represent a manifestation of denervation caused by visceral neuropathy. Based on normal post-prandial cholecystokinin release, it can be ruled out that impaired cholecystokinin release is the mechanism responsible for reduced gall-bladder emptying in diabetics. Other possible explanations for impaired gall-bladder contraction in diabetics include a decreased sensitivity of the smooth muscle of the gall-bladder to plasma cholecystokinin, and/or decreased cholecystokinin receptors on the gall-bladder wall.
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Affiliation(s)
- P Pazzi
- Department of Gastroenterology, S. Anna Hospital, Ferrara, Italy.
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20
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Lonovics J, Madácsy L, Szepes A, Szilvássy Z, Velösy B, Varró V. Humoral mechanisms and clinical aspects of biliary tract motility. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1998; 228:73-89. [PMID: 9867117 DOI: 10.1080/003655298750026606] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
This review is intended to summarize current information on neurohumoral regulation of the gallbladder and sphincter of Oddi motility under both physiological and pathological circumstances with emphasis on Hungarian contributions to today's knowledge. The mechanism of action of neurohumoral agents that interact on these segments of the biliary tract, and the explored details of the stimulation-contraction/relaxation coupling process of these substances, will be discussed. A modified classification of biliary tract motility disorders with new diagnostic and therapeutic approaches will also be provided. This information will aid understanding of the pathogenesis of motor disorders of the gallbladder and sphincter of Oddi, and will indicate possibilities for pharmacological exploitation in the treatment of diseases resulting from biliary tract motility abnormalities.
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Affiliation(s)
- J Lonovics
- First Dept. of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary
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21
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Abstract
Diabetes mellitus can lead to metabolic changes that alter normal hepatic and biliary function and structure. These alterations in hepatic and biliary function and structure are usually benign, but in certain situations lead to significant, disabling disease. This article reviews the hepatic and biliary complications of diabetes, with emphasis on epidemiology, diagnosis, and management, as well as the glucose intolerance seen in liver disease.
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Affiliation(s)
- F J Farrell
- Department of Medicine, University of California, San Francisco/Mount Zion Medical Center, San Francisco, USA
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Meguro T, Shimosegawa T, Satoh A, Suzuki H, Takasu A, Takayama A, Koizumi M, Toyota T. Gallbladder emptying and cholecystokinin and pancreatic polypeptide responses to a liquid meal in patients with diabetes mellitus. J Gastroenterol 1997; 32:628-34. [PMID: 9349988 DOI: 10.1007/bf02934112] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
To investigate gallbladder motility and its regulation in patients with diabetes mellitus (DM), we examined the gallbladder response to an intraduodenal test meal by measuring the temporal course of plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels. Eighteen patients with type 2 DM and 7 healthy subjects (controls) were enrolled. The gallbladder volume was calculated by the sum-of-cylinders method from ultrasonographic images, and plasma CCK and PP were measured by radioimmunoassays. No significant difference was found in either the gallbladder response or in the CCK response between patients with DM and controls. However, the fasting plasma PP level of patients with DM was more than tenfold higher than that of controls. The integrated PP response (IPPR) of patients with DM to the test meal was 8.3-fold higher than that of controls. When patients with DM were grouped according to whether they had been treated with insulin or not, the fasting plasma PP of patients with DM without insulin treatment was significantly higher than the level in those treated with insulin. These results suggest that overproduction of PP-like immunoreactive substance(s) may occur in patients with DM, but the high plasma PP immunoreactivity does not appear to be related to the fasting gallbladder volume or to gallbladder emptying and filling.
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Affiliation(s)
- T Meguro
- Third Department of Internal Medicine, Tohoku University School of Medicine, Miyagi, Japan
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23
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Portincasa P, Di Ciaula A, Palmieri V, Van Berge-Henegouwen GP, Palasciano G. Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects. Eur J Clin Invest 1995; 25:746-753. [PMID: 8557061 DOI: 10.1111/j.1365-2362.1995.tb01953.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through disinhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by real-time ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4 g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 +/- 6.9 vs. 21.6 +/- 1.7 mL, P < 0.02), larger residual volume (12.3 +/- 1.8 vs. 4.0 +/- 0.5 ml, P < 0.0006) and slower emptying time (T/2: 33 +/- 2 vs. 21 +/- 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 +/- 578 vs. 7908 +/- 491 %120 min-1, P < 0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.
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Affiliation(s)
- P Portincasa
- Institute of Clinica Medica I, University of Bari Medical School, Italy
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Portincasa P, Stolk MF, van Erpecum KJ, Palasciano G, van Berge-Henegouwen GP. Cholesterol gallstone formation in man and potential treatments of the gallbladder motility defect. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1995; 212:63-78. [PMID: 8578234 DOI: 10.3109/00365529509090303] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Cholelithiasis affects 10-15% of the adult population in Western society, and about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of cholesterol with the formation of instable cholesterol-rich vesicles in bile, an imbalance between nucleation-inhibiting and nucleation-promoting proteins with further aggregation of cholesterol crystals in a gallbladder with a motility defect (stasis), all play a role in the pathogenesis of cholesterol gallstones. Experimental animal models suggest that gallstone formation can be prevented by improving gallbladder emptying. Thus, a better understanding of the causes underlying the impaired gallbladder motor function in patients with gallstones might lead to the selection of therapeutic approaches for those individuals who are at increased risk for the formation or recurrence of gallstones. The present article focuses on current concepts and theories on the pathogenesis of cholesterol gallstones with emphasis on the gallbladder motility defect. Several treatment strategies for the correction of gallbladder hypomotility are also discussed.
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Affiliation(s)
- P Portincasa
- Dept. of Gastroenterology, University Hospital Utrecht, The Netherlands
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25
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Paro M, Prashar A, Prosdocimi M, Cherian PV, Fiori MG, Sima AA. Urinary bladder dysfunction in the BB/W diabetic rat: effect of ganglioside treatment on functional and structural alterations. J Urol 1994; 151:781-6. [PMID: 8309006 DOI: 10.1016/s0022-5347(17)35087-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Urinary bladder dysfunction in the diabetic BB/W rat is characterized by infrequent irregular contractions of high amplitude. Initially these occur in the absence of detectable neuroanatomical lesions of sensory afferent and parasympathetic fibers of the pelvic nerve, which constitute the micturition reflex arc. Structural lesions consisting of progressive axonal atrophy of myelinated and unmyelinated fibers become detectable only after 4 months of diabetes. In the current study we evaluated the effect of ganglioside treatment (10 mg./kg. body weight) for one month. This drug regimen was initiated at 4 months of diabetes, when functional bladder abnormalities were well established, whereas structural lesions were yet to appear. Animals examined 1 or 3 months after termination of the one-month treatment protocol showed sustained normalization of the characteristic functional abnormalities, accompanied by prevention of the neuroanatomical lesions of sensory afferent and parasympathetic efferent myelinated fibers in the pelvic nerve. These data suggest that ganglioside treatment may be beneficial in delaying the progression of diabetic autonomic neuropathy in this experimental animal model.
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Affiliation(s)
- M Paro
- FIDIA Research Laboratories, Abano Terme (PD), Italy
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