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PubMed2000

Asthma: pathophysiology of the bronchial obstruction.

From a pathophysiologic perspective, the changes that occur in asthma are multiple, diverse, and complex. Assessment of the mechanical properties of the ventilatory apparatus provides several different types of information, depending on the gravity of the bronchial obstruction. During asthma, or induced bronchial obstruction, the function of the muscles is altered, causing changes in respiratory timing. Expiratory duration decreases more than inspiratory duration, and the functional residual capacity (FRC) increases, due to mechanical changes within the airways that lead to air trapping. The related hypoventilation is responsible for hypoxemia and hypercapnia, but it does not severely affect the diffusion capacity of the alveolocapillary membrane. We describe the pathophysiology of the bronchial obstruction in asthmatic patients, underlining the critical function of the respiratory muscles. Moreover, we clarify the relations between the ventilatory changes and gas-exchange alteration.

Airway Obstruction↗
PubMed2002

The pathophysiological basis of acute-on-chronic liver failure.

The vast majority of patients that are referred to a specialist hepatological centre suffer from acute deterioration of their chronic liver disease. Yet, this entity of acute-on-chronic liver failure remains poorly defined. With the emergence of newer liver support strategies, it has become necessary to define this entity, its pathophysiology and the short and long-term prognosis. This review focuses upon how a precipitant such as an episode of gastrointestinal bleeding or sepsis may start a cascade of events that culminate in end-organ dysfunction and liver failure. We briefly review the pathophysiological basis of the therapeutic modalities that are available. Our current strategy for the management of liver failure involves supportive therapy for the end-organs with the hope that the liver function would recover if sufficient time for such a recovery is allowed. Because liver failure, whether of the acute or acute-on-chronic variety, is potentially reversible, the stage is set for the application of newer liver support strategies to enhance the recovery process.

Acute Disease↗
PubMed2001

Multiple sclerosis: current pathophysiological concepts.

Multiple sclerosis (MS) is an often disabling disease primarily affecting young adults that exhibits extraordinary clinical, radiological, and pathological heterogeneity. We review the following: (a) known environmental and genetic factors that contribute to MS susceptibility; (b) current knowledge regarding fundamental pathophysiological processes in MS, including immune cell recruitment and entry into the central nervous system (CNS), formation of the plaque, and orchestration of the immune response; (c) descriptive and qualitative distinct pathological patterns in MS and their implications; (d) the evidence supporting the causative role of direct toxins, cell-mediated and humorally mediated immune mechanisms, and the concept of a "primary oligodendrogliopathy" in demyelination and axonal injury; (e) the potential benefits of inflammation; (f) the prospects for remyelination; and (g) therapeutic implications and approaches suggested by putative pathophysiological mechanisms.

Humans↗
PubMed1997

Mapping pathophysiological features of breast tumors by MRI at high spatial resolution.

Magnetic resonance imaging (MRI) is a noninvasive method that reveals anatomical details in vivo and detects lesions for diagnosis. Although standard breast MRI cannot clearly delineate breast cancer, contrast-enhanced MRI enables the detection of breast masses with high sensitivity. Dynamic studies demonstrated that malignant lesions were characterized by a faster signal enhancement rate than benign ones. Dynamic MRI of human breast cancer in mice revealed high heterogeneity in the distribution of contrast-enhanced curves and derived pathophysiological features, indicating the importance of high spatial resolution. With clinical MRI, it is difficult to achieve simultaneously high spatial and temporal resolution. In previous dynamic studies, the emphasis was on high temporal resolution and mainly empiric analyses. We describe here a new model-based method that optimizes spatial resolution by using only three time points, and yet characterizes tumor heterogeneity in terms of microvascular permeability and extracellular fraction. Mapping these pathophysiological features may aid diagnosis and prognosis assessment, while the high spatial resolution may improve the capacity to detect smaller lesions. The method was tested in human breast tumors implanted in mice and in a limited number of benign and malignant breast lesions of patients.

Animals↗
PubMed2002

Implications of nitric oxide synthase isoforms in the pathophysiology of Peyronie's disease.

Peyronie's disease is an idiopathic, localized connective tissue disorder of the penis which involves the tunica albuginea of the corpus cavernosum and the adjacent areolar space. Peyronie's disease is characterized by local changes in the collagen and elastic fiber composition of the tunica albuginea. The formation of fibrotic plaques alters penile anatomy and can cause different degrees of bending and narrowing, as well as penile pain and erectile dysfunction. Though long recognized as an important clinical entity of the male genitalia, the etiology of this disease has remained poorly understood. Until recently there have been no studies to examine the role nitric oxide (NO) and nitric oxide synthase (NOS) isoforms may play in the onset and progression of Peyronie's disease. NO is a potent biological mediator with diverse physiological and pathophysiological roles. The purpose of this review is to describe each of the NOS isoforms and their potential roles in the pathophysiology of Peyronie's disease, with particular emphasis on the regulation of endothelial and inducible NOS isoforms.

Animals↗
PubMed1998

Isolated systolic hypertension: pathophysiology, consequences and therapeutic benefits.

During recent decades the importance of perceiving isolated systolic hypertension (ISH) in cardiovascular pathophysiology has been changed from a benign condition to the major cardiovascular risk factor. Aging is per se associated with the deterioration in arterial compliance through both structural and functional changes in large arteries which mainly involves the intima and media. The observed changes result in a decrease of the lumen-to-wall ratio, the overall lumen cross-sectional area and an increase of arterial stiffness which especially involve the aorta and other elastic arteries. In addition to the structural changes in vessel walls, aging is associated with certain functional changes such as an increase in sympathetic system activity probably due to the age-related decreased sensitivity of beta-receptors. While the function of arterial wall alpha-receptors remains intact, in elderly subjects a shift towards arterial vasoconstriction can be observed. In many of the published studies the definition of ISH was based on the criterion 160/95 mm Hg or 160/90 mm Hg while in recognition of the high risk associated with systolic blood pressure (SBP) the WHO/ISH guidelines and Report of the Sixth Joint National Committee on Hypertension indicated that ISH should be diagnosed with SBP as > or =140 mm Hg and diastolic BP (DBP) as <90 mm Hg. Thus the setting down of normal values of SBP will lead to an earlier diagnosis and treatment of ISH. Several prospective studies, such as the US Hypertension Detection and Follow-up Programme, confirmed this and the Multiple Risk Factor Intervention Trial demonstrated that for any given level of DBP, higher SBP was associated with an increase in cardiovascular risk. Moreover, data from the Framingham Study show that ISH was associated not only with increased mortality but also cardiovascular morbidity. Risk of non-fatal stroke and myocardial infarction was increased three and two-times respectively in the presence of ISH. Three major up-to-date studies that included patients with ISH have been published. In concordance to the previously published SHEP and MCR trials, the most recent, the Systolic Hypertension in the Elderly Trial (SYST-EUR), demonstrated that active treatment significantly reduces the risk of stroke and all fatal and non-fatal cardiac end-points, including sudden death. Of note, these benefits were demonstrated with new anti-hypertensive classes such as dihydropiridyne calcium channel blocker (nitrendipine) and the angiotensin-converting enzyme inhibitor (enalapril). The necessity to carefully balance the benefits and risks of anti-hypertensive therapy in the elderly indicates that patients with suspected ISH should undergo careful BP measurements on at least three different occasions before the diagnosis is established and an orthostatic reaction should be evaluated. If non-pharmacological procedures fail, drug therapy should be considered, especially in elderly patients with a SBP over 160 mm Hg, since their risk of complications is markedly higher. Pharmacological treatment should also be strongly considered in patients with a SBP between 140 and 160 mm Hg with such concomitant cardiovascular risk factors as diabetes, angina pectoris, and left ventricular hypertrophy. The drug regimen should be simple, starting with a low dose of a single drug that is titrated slowly. The selection of the first-line anti-hypertensive agent should be based on a careful assessment of pathophysiological and clinical parameters in each individual geriatric patient.

Age Distribution↗
PubMed2006

Contrast medium-induced nephropathy: the pathophysiology.

A widespread, rather general, definition of contrast-induced nephropathy (CIN) is an impairment in renal function occurring within 3 days following the intravascular administration of contrast media (CM) and the absence of an alternative aetiology. In spite of the vast clinical importance of CIN, its understanding and the pathophysiology behind CIN remain incomplete. Many studies have been performed; however, they have provided no widely accepted conclusion so far. Here the possible mechanisms underlying CIN are outlined, which span from altered rheological properties, perturbation of renal haemodynamics, regional hypoxia, auto-, and paracrine factors (adenosine, endothelin, reactive oxygen species) to direct cytotoxic effects. Although these potential mediators of CIN will be discussed separately, several factors may act in concert to perturb kidney function after exposure to contrast media. From the current knowledge of the mechanisms causing CIN, it is not possible to recommend a certain class of contrast media, except to avoid large doses of CM of the first generation. From a pathophysiological perspective, volume expansion is effective in avoiding CIN, since water permeability of the collecting ducts will decrease and enhance fluid excretion. Hence, CM in the distal portions of the tubular system is diluted, which implies reduced fluid viscosity and a lower risk of obstruction.

Coloring Agents↗
PubMed1997

Interleukin 1 receptor antagonist gene expression in rat pituitary in the systemic inflammatory response syndrome: pathophysiological implications.

The systemic inflammatory response syndrome (SIRS) is characterized by endothelial cell activation causing a generalized inflammatory response and cytokine-mediated pathophysiological alterations. The pathophysiology of SIRS involves changes in the functioning of several endocrine glands, including the pituitary. SIRS-induced alterations in pituitary function include activation of the hypothalamic-pituitary adrenal (HPA) axis causing hypercortisolemia, the euthyroid sick syndrome, and cessation of reproductive function. These changes are in part mediated by cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1). IL-1 function depends on the local ratio of bioactive IL-1 and IL-1 receptor antagonist. Here we review our studies on IL-1 beta and IL-1ra mRNA levels in the pituitary in a rat model of SIRS. We have found that IL-1 beta mRNA peaked at 2 h after lipopolysaccharide (LPS) administration, increasing twelvefold over control values in the posterior pituitary and fivefold over controls in the anterior pituitary. IL-1ra mRNA levels peaked at 6 h post-LPS administration, later than those of IL-1 beta mRNA. IL-1ra mRNA levels increased tenfold in the anterior pituitary, but were induced only threefold in the posterior pituitary. IL-1ra gene expression is profoundly induced in the pituitary in vivo during systemic inflammation and its induction follows that of IL-1 beta, but it is differentially regulated and tissue-specific, occurring predominantly in the anterior pituitary. Future studies of the effects of IL-1 in the pituitary should take into account the local levels of IL-1ra.

Animals↗
PubMed2004

Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiology.

Bipolar affective disorder (manic-depressive illness) is a common, severe, chronic, and often life-threatening illness, associated with significant comorbidity. The recognition of the significant morbidity and mortality of patients with bipolar disorder, as well as the growing appreciation that a high percentage of patients respond poorly to existing treatments, has made the task of discovering new therapeutic agents, that are both efficacious and have few side effects increasingly more important. Most recent agents introduced into the pharmacopeia for the treatment of bipolar disorder have been anticonvulsants and atypical antipsychotics. We propose that novel treatments developed specifically for bipolar disorder will arise from (1) understanding more precisely the molecular mechanisms of treatments that are clearly efficacious or (2) developing medications based on the knowledge obtained of the underlying pathophysiology of bipolar disorder. Knowledge with regard to the underlying pathophysiology of bipolar disorder is increasing at a rapid pace, including alterations in intracellular signaling cascades as well as impairments of cellular plasticity and resilience in critical neuronal circuits. We propose that therapeutics designed to enhance cellular plasticity and resilience and that counter maladaptive stress-responsive systems may have considerable utility for the treatment of bipolar disorder. Therapeutic strategies designed to address cellular resilience and plasticity include the regulation of neurotrophic pathways, glucocorticoid signaling, phosphodiesterase activity, and glutamatergic throughput and mitochondrial function. While the task of developing novel medications for bipolar disorder is truly daunting, these and similar approaches will ultimately lead to better medications for the millions who suffer from this devastating illness.

Antimanic Agents↗
PubMed2006

Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics.

Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics. We therefore investigated neuroactive steroid levels in post-mortem brain tissue from subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects to determine if neuroactive steroids are altered in these disorders. Posterior cingulate and parietal cortex tissue from the Stanley Foundation Neuropathology Consortium collection was analyzed for neuroactive steroids by negative ion chemical ionization gas chromatography/mass spectrometry preceded by high-performance liquid chromatography. Subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects were group matched for age, sex, ethnicity, brain pH, and post-mortem interval (n = 14-15 per group, 59-60 subjects total). Statistical analyses were performed by ANOVA with post-hoc Dunnett tests on log transformed neuroactive steroid levels. Pregnenolone and allopregnanolone were present in human post-mortem brain tissue at considerably higher concentrations than typically observed in serum or plasma. Pregnenolone and dehydroepiandrosterone levels were higher in subjects with schizophrenia and bipolar disorder compared to control subjects in both posterior cingulate and parietal cortex. Allopregnanolone levels tended to be decreased in parietal cortex in subjects with schizophrenia compared to control subjects. Neuroactive steroids are present in human post-mortem brain tissue at physiologically relevant concentrations and altered in subjects with schizophrenia and bipolar disorder. A number of neuroactive steroids act at inhibitory GABA(A) and excitatory NMDA receptors and demonstrate neuroprotective and neurotrophic effects. Neuroactive steroids may therefore be candidate modulators of the pathophysiology of schizophrenia and bipolar disorder, and relevant to the treatment of these disorders.

Analysis of Variance↗
PubMed1999

Spinal shock and brain death': somatic pathophysiological equivalence and implications for the integrative-unity rationale.

The somatic pathophysiology of high spinal cord injury (SCI) not only is of interest in itself but also sheds light on one of the several rationales proposed for equating 'brain death' (BD) with death, namely that the brain confers integrative unity upon the body, which would otherwise constitute a mere conglomeration of cells and tissues. Insofar as the neuropathology of BD includes infarction down to the foramen magnum, the somatic pathophysiology of BD should resemble that of cervico-medullary junction transection plus vagotomy. The endocrinologic aspects can be made comparable either by focusing on BD patients without diabetes insipidus or by supposing the victim of high SCI to have pre-existing therapeutically compensated diabetes insipidus. The respective literatures on intensive care for BD organ donors and high SCI corroborate that the two conditions are somatically virtually identical. If SCI victims are alive at the level of the 'organism as a whole', then so must be BD patients (the only significant difference being consciousness). Comparison with SCI leads to the conclusion that if BD is to be equated with death, a more coherent reason must be adduced than that the body as a biological organism is dead.

Brain Death↗
PubMed2003

Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiology.

The molybdo-flavoenzymes are structurally related proteins that require a molybdopterin cofactor and FAD for their catalytic activity. In mammals, four enzymes are known: xanthine oxidoreductase, aldehyde oxidase and two recently described mouse proteins known as aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2. The present review article summarizes current knowledge on the structure, enzymology, genetics, regulation and pathophysiology of mammalian molybdo-flavoenzymes. Molybdo-flavoenzymes are structurally complex oxidoreductases with an equally complex mechanism of catalysis. Our knowledge has greatly increased due to the recent crystallization of two xanthine oxidoreductases and the determination of the amino acid sequences of many members of the family. The evolution of molybdo-flavoenzymes can now be traced, given the availability of the structures of the corresponding genes in many organisms. The genes coding for molybdo-flavoenzymes are expressed in a cell-specific fashion and are controlled by endogenous and exogenous stimuli. The recent cloning of the genes involved in the biosynthesis of the molybdenum cofactor has increased our knowledge on the assembly of the apo-forms of molybdo-flavoproteins into the corresponding holo-forms. Xanthine oxidoreductase is the key enzyme in the catabolism of purines, although recent data suggest that the physiological function of this enzyme is more complex than previously assumed. The enzyme has been implicated in such diverse pathological situations as organ ischaemia, inflammation and infection. At present, very little is known about the pathophysiological relevance of aldehyde oxidase, aldehyde oxidase homologue 1 and aldehyde oxidase homologue 2, which do not as yet have an accepted endogenous substrate.

Aldehyde Oxidase↗
PubMed2006

IRES-dependent regulation of FGF-2 mRNA translation in pathophysiological conditions in the mouse.

The mRNA coding for FGF-2 (fibroblast growth factor 2), a major angiogenic factor, is translated by an IRES (internal ribosome entry site)-dependent mechanism. We have studied the role of the IRES in the regulation of FGF-2 expression in vivo, under pathophysiological conditions, by creating transgenic mice lines expressing bioluminescent bicistronic transgenes. Analysis of FGF-2 IRES activity indicates strong tissue specificity in adult brain and testis, suggesting a role of the IRES in the activation of FGF-2 expression in testis maturation and brain function. We have explored translational control of FGF-2 mRNA under diabetic hyperglycaemic conditions, as FGF-2 is implied in diabetes-related vascular complications. FGF-2 IRES is specifically activated in the aorta wall in streptozotocin-induced diabetic mice, in correlation with increased expression of endogenous FGF-2. Thus, under hyperglycaemic conditions, where cap-dependent translation is blocked, IRES activation participates in FGF-2 overexpression, which is one of the keys of diabetes-linked atherosclerosis aggravation. IRES activation under such pathophysiological conditions may involve ITAFs (IRES trans-acting factors), such as p53 or hnRNP AI (heterogeneous nuclear ribonucleoprotein AI), recently identified as inhibitory or activatory ITAFs respectively for FGF-2 IRES.

Animals↗
PubMed2001

Pathophysiology of acute pain: implications for clinical management.

To effectively treat acute pain, emergency medicine practitioners must have a thorough understanding of both the pathophysiology and terminology of the pain experience. The pathophysiology of pain is discussed with an emphasis on the mechanisms of acute, inflammatory pain. The various types of pain receptors, pathways and neurotransmitters are also discussed.

Acute Disease↗
PubMed2003

Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice.

AIM: There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology. OBESITY-RELATED HYPERTENSION: An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of beta3-adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post-ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity-related hypertension, but this has not been adequately tested. ESSENTIAL HYPERTENSION: Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress. CARDIAC FAILURE: At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50-fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of beta-adrenergic blockers for treatment of heart failure.

Autonomic Nervous System Diseases↗
PubMed1997

The pathophysiological mechanism of fluid retention in advanced cancer patients treated with docetaxel, but not receiving corticosteroid comedication.

AIMS: Fluid retention is a phenomenon associated with taxoids. The principal objective of this study was to investigate the pathophysiological mechanism of docetaxel-induced fluid retention in advanced cancer patients. METHODS: Docetaxel was administered as a 1 h intravenous infusion every 3 weeks, for at least 4-6 consecutive cycles, to patients with advanced breast (n = 21) or ovarian (n = 3) carcinoma, who had received previous chemotherapy, 21 for advanced disease. Phase II clinical trials have shown that 5 day corticosteroid comedication, starting 1 day before docetaxel infusion, significantly reduces the incidence and severity of fluid retention. This prophylactic corticosteroid regimen is currently recommended for patients receiving docetaxel but was not permitted in this study because of its possible interference with the underlying pathophysiology of the fluid retention. RESULTS: Fluid retention occurred in 21 of the 24 patients but was mainly mild to moderate, with only five patients experiencing severe fluid retention. Eighteen patients received symptomatic flavonoid treatment, commonly prescribed after the last cycle. Specific investigations for fluid retention confirmed a relationship between cumulative docetaxel dose and development of fluid retention. Capillary filtration test analysis showed a two-step process for fluid retention generation, with progressive congestion of the interstitial space by proteins and water starting between the second and the fourth cycle, followed by insufficient lymphatic drainage. CONCLUSIONS: A vascular protector such as micronized diosmine hesperidine with recommended corticosteroid premedication and benzopyrones may be useful in preventing and treating docetaxel-induced fluid retention.

Adenocarcinoma↗
PubMed2000

Sperm ultramorphology as a pathophysiological indicator of spermatogenesis in males suffering from varicocele.

Varicocele of spermatic veins is considered to be one of the major causes of male infertility associated with reduction of sperm quality. The pathophysiology of this condition is not yet completely understood. The aim of this study was to shed light on the pathophysiology of varicocele by identifying semen parameters, especially sperm ultramorphology, which improve following high ligation of the spermatic vein. Seventy-five males with diagnosed varicocele were included in this study. Semen parameters were assessed prospectively using light microscopy, semen biochemistry and sperm quantitative ultramorphological analysis, before high ligation and 3-9 months after high ligation. The control group consisted of twenty-five untreated varicocele patients who underwent two semen examinations within 3-9 months. No statistical difference in any of the examined variables was found between the two examinations in the control group. The treated patients exhibited a significant improvement in sperm density, progressive motility, percentage of normally formed spermatozoa, agenesis of sperm acrosome, chromatin condensation and incidence of amorphous heads compared with the pretreatment condition (P < or = 0.01). In contradiction, no significant improvement was observed following treatment in any of the sperm tail subcellular organelles. It is concluded that varicocele may cause deleterious alterations in early spermatid head differentiation during spermiogenesis and that varicocele patients with a high incidence of sperm acrosome and nucleus malformations are appropriate candidates for varicocele correction.

Adult↗
PubMed2000

Pathophysiology of the intrahepatic biliary epithelium.

The intrahepatic bile duct epithelium modulates the fluidity and alkalinity of the primary hepatocellular bile from which it reabsorbs fluids, amino acids, glucose and bile acids, while secreting water, electrolytes and immunoglobulin A. The transport function of the intrahepatic biliary epithelium is finely regulated by a number of gastrointestinal hormones, neuropeptides and neurotransmitters that promote either secretion or absorption. The intrahepatic biliary epithelium appears to be a primary target in a broad group of chronic cholestatic disorders that represent an important cause of morbidity and mortality. The spectrum of cholangiopathies ranges from conditions in which a normal epithelium is damaged by disordered autoimmunity, infectious agents, toxic compounds or ischaemia, to genetically determined disorders arising from an abnormal bile duct biology, such as cystic fibrosis or biliary atresia. Probably as a result of the known heterogeneity in cholangiocyte function, different portions of the biliary tree appear to be preferentially affected in specific cholangiopathies. From a pathophysiological point of view, cholangiopathies are characterized by the coexistence of cholangiocyte loss (by apoptotic or lytic cell death) with cholangiocyte proliferation and various degrees of portal inflammation, fibrosis and cholestasis. These basic disease mechanisms are discussed in detail. Better understanding of cholangiocyte pathophysiology, in particular the immune regulation of cholangiocyte function, will help in designing newer genetic or pharmacological approaches to treat cholangiopathies.

Absorption↗