A CASE REPORT REGARDING MANAGEMENT OF KAMALA THROUGH AYURVEDA

Ayurveda is traditionally skilful in treating liver diseases for centuries. Although named Jaundice as a liver disorder was not mentioned in Ayurveda literature but based on common characteristics and Pathology, Kamala can be correlated with jaundice. Jaundice is a clinical manifestation of disorders of underlying bilirubin metabolism, hepa- tocellular dysfunction, or biliary obstruction. Jaundice occurs in settings of cholestasis or inability to effectively secrete bile as well as disorders of bilirubin metabolism and hepatocellular dysfunction. Today's lifestyle with un- hygienic and poor dietary habits and alcoholic habits, etc are responsible factors to promote hepatic damage which is clinically reflected as Kamala. This paper discusses a patient seen in the OPD of Kayachikitsa Quadra Institute of Ayurveda Roorkee Haridwar. Her chief complaints Udara shool (pain in the abdomen), Kshudha Mandhya (loss of appetite), Daurbalya (weakness), Hrullas (Nausea), Mutrapitata (yellow discolouration of urine, Vibhandha (constipation) for 15 days. This patient was effectively treated by the combination of Kutaki Churna, Triphala, Trivrita Churna, Bhunimba Churna, Arogya Vardhini Vati, Phalatrikadi Kashaya, Punarnava Mandoor and Liv 52. All the symptoms showed highly significant results. Hence it can be concluded that these medicines are very effective in patients with jaundice. Keywords: Udara shool, Kshudha mandhya, Daurbalya, Hrullas, Mutrapitata, Vibhandha.

Liver dysfunction in idiopathic pulmonary arterial hypertension: prevalence, characteristics and prognostic significance, a retrospective cohort study in China

ObjectivesThe aim was to elucidate the relationship between liver function and idiopathic pulmonary arterial hypertension (IPAH).Design and settingRetrospective, longitudinal study in urban tertiary care centre in Shanghai, China.Participants407 IPAH consecutive incident patients age 18–65 years were retrospectively enrolled from January 2008 to December 2018.Outcome measurementsThe primary endpoint was all-cause mortality. The cut-off value was determined by receiver operating characteristic curve (ROC), which was validated by Cox proportional hazard model was internally validated by bootstrap analysis and used for survival analysis. The Cox model was (internally) validated and cross-validated areas under the curve (AUC) should be reported.ResultsThe prevalence of abnormal liver function tests (LFTs) at baseline was 77.6%. Hyperbilirubinaemia is the most common abnormal biochemical liver test: abnormal total bilirubin (TBIL in 51.6% patients). During the follow-up, 160 patients died. Patients with mixed liver dysfunction have worse prognosis than those with normal LFTs or isolated abnormal bilirubin metabolism. Comparing with patients with hepatocellular injury, the survival of patients with abnormal bilirubin metabolism is lower. Multivariable Cox models revealed a positive association between TBIL, γ-glutamyltransferase (GGT) and mortality showing that each Ig increment in TBIL and GGT was associated with a higher all-cause mortality (TBIL: HR 4. 29 (95% CI 1. 21 to 15. 27), p=0. 02; GGT: HR 2. 76 (95% CI 1. 18 to 6. 45), p=0. 02). A novel formula named Liver Function Predict Index (LFPI) was constructed (LFPI=−0.002*6MWD+1.014*lg GGT+1.458*lg TBIL) to predict prognosis. ROC curve analysis did further identify 2.729 as the best cut-off value for LFPI (AUC 0.75, p<0.001, sensitivity 79%, specificity 70%).ConclusionsLiver dysfunction is frequent in IPAH, and characterised by a predominantly cholestatic enzyme profile. LFTs abnormalities are associated with worse survival and LFPI was a new and simple predictor for prognosis of IPAH.

How dangerous Gilbert's syndrome is

Gilbert's syndrome is a benign (functional) hyperbilirubinemia, which is based on a hereditary disorder of bilirubin metabolism, as a result of which the concentration of unbound bilirubin can increase several times. Bilirubin, being a breakdown product of hemoglobin, circulates through the bloodstream, combining with albumin molecules. Such bilirubin is called indirect. In the endoplasmic reticulum, it is conjugated; the enzyme glucuronyltransferase is responsible for this process. In Gilbert's syndrome, as a result of insufficient production of this enzyme, the conjugation process is disrupted, and, as a result, the concentration of unconjugated bilirubin increases. According to statistics, this pathological condition is observed in about 5 % of Russians. This syndrome was first described in 1901 by the French physician Augustin Nicolas Gilbert, and was subsequently named after him. The literature also contains references to this syndrome, described as «constitutional hepatic dysfunction», «familial non-hemolytic hyperbilirubinemia», «idiopathic non-conjugated hyperbilirubinemia». Gilbert's syndrome is inherited in an autosomal recessive manner; men get ill 3–4 times more often than women. A number of scientists associate this with a possible inhibitory effect of testosterone on the enzyme UDP-GT1, which breaks down bilirubin. Clinically, Gilbert's syndrome is manifested by episodes of jaundice caused by an increase in the level of unconjugated bilirubin in the blood serum. Against the background of icterus of the sclera and skin, there is increased fatigue, the appearance of a feeling of bitterness in the mouth, loss of appetite, nausea, and sometimes vomiting. The association of Gilbert's syndrome with functional disorders of the biliary tract, in particular, with gallbladder dyskinesia, is often noted.

Changes of Serum Bilirubin and Urine Peptides Related to Bilirubin Metabolism in Patients with Allergic Rhinitis

Background: The incidence rate of allergic rhinitis (AR) has been increasing, which has become a global health problem. As a kind of inflammatory airway disease, allergic rhinitis has a large number of inflammatory cells and inflammatory mediators that participate. Bilirubin is an effective endogenous antioxidant and anti-inflammatory molecule. This study aims to explore the relationship between bilirubin and allergic rhinitis, and to explore the potential value of bilirubin-related metabolites in blood and urine in the assessment of AR disease. Methods: A total of 63 allergic rhinitis (AR-S group) patients and 86 healthy controls (NC-S group) were enrolled. Venous blood was obtained for measurement of serum total IgE levels and bilirubin parameters. Patients were classified into normal IgE level group (AR2-S group) and elevated IgE level group (AR1-S group). Ten subjects were randomly selected from each group, which were AR2 group, AR1 group and NC group. Urine samples were measured with the nano UPLC-MS/MS system consisting of a Nanoflow HPLC system (EASY-nLC 1000 system from Thermo Scientific) and Orbitrap Fusion Lumos mass spectrometer (Thermo Scientific). Results: The mean total TBIL level (12.5 vs 15.7 μmol /L, p <0.001), median total DBIL level (4.4 vs 5.3 μmol /L, p <0.001) and mean total IBIL level (8.1 vs 10.3 μmol/L, p <0.001) in AR-S group were significantly lower than those in NC-S group. The mean total TBIL level (13.1 vs 15.7 μmol /L, p = 0.007), median total DBIL level (4.74 vs 5.3 μmol /L, p = 0.022), and mean total IBIL level (8.39 vs 10.3 μmol/L, p = 0.005) in AR2-S were significantly lower than those in NC-S group. The median total TBIL level (12.0 vs 15.7 μmol /L, p < 0.001), median total DBIL level (4.09 vs 5.3 μmol /L, p < 0.001), and median total IBIL level (7.91vs 10.3 μmol/L, p <0.001) in AR1-S were significantly lower than those in NC-S group. In addition, we found that there were 15 urine differential proteins related to bilirubin metabolism in AR2 and AR1. Their relative expression levels increased or decreased successively in NC group, normal IgE level group (AR2) and increased IgE level group (AR1). Conclusions: Compared with healthy people, the levels of bilirubin metabolites in patients with allergic rhinitis were decrease in the blood. The levels of bilirubin metabolites in urine of patients with allergic rhinitis have changed. This result suggests that bilirubin may be a new target for AR diagnosis and treatment.

Abstract P756: Bilirubin Oxidation and Cerebral Vasospasm in Subarachnoid Hemorrhage: A Feasibility Study

Introduction: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high degree of morbidity and mortality. In an adequate oxidative environment, certain products of bilirubin metabolism have been hypothesized to be a cause of CV. To our knowledge no prospective CSF collection has been performed to establish a time course for their formation in the clinical context of CV. We aimed to design a pilot study assessing the feasibility of collecting and storing CSF for analysis of potential biochemical markers for CV, and to evaluate which variables can accurately and reliably be measured for a larger prospective study. Methods: Adult patients with aSAH and an external ventricular drain (EVD) were enrolled. Patients who had complications following treatment of aSAH or who developed any neurological deterioration unrelated to the aSAH were excluded. CSF was extracted from patients on the initial day of EVD placement and then daily for a total of 10 days and frozen until data analysis. Heme, Heme Oxygenase (HO-1) and Cu/Zn-Superoxide Dismutase (SOD) were measured using commercially available assay kits. Results: Patients 1, 2 and 3 had modified Fisher grades of 2, 3 and 4, respectively. Patients 1 and 3 underwent endovascular coiling and patient 2 had surgical clipping. There were no complications and no CV. Heme concentrations were 40.0 ± 8.5 μm, 55.6 ± 7.7 μm, and 64.7 ± 0.4 μm on day of bleed (day 0) for patients 1, 2, and 3, respectively, and decreased in patients 1 and 2 on day 1. SOD concentrations peaked on day 2 for patient 1 (140.2 ± 15.6 ng/mL), on day 0 for patient 2 (25.8 ± 14.9 ng/mL), and on day 1 for patient 3 (215.9 ± 24.4 ng/mL). HO-1 concentrations peaked for all three patients on day 2 (14.6 ± 0.4, 17.6 ± 12.0 and 23.6 ± 5.4 ng/mL, respectively). Conclusions: The study was successful in completing our objective of establishing a protocol for collection, storage, and measurement of three potential biochemical markers in CSF. A larger prospective study will be performed to establish the time course of bilirubin metabolism and oxidation in the CSF relative to the clinical condition of CV in patients after aSAH.

Identifying UGT1A1 gene mutations in Vietnamese patients with Gilbert syndrome

Gilbert’s syndrome (GS) is the most common inherited disorder of bilirubin metabolism, non-lethal, affecting 3-12% of the population. The genetic variants of the UDP- glucuronosyltransferase 1A1 (UGT1A1) gene might reduce the gene transcription activity and its enzyme expression, which affects the ability to conjugate glucuronidation in the liver. This study aimed to identify genetic variants of UGT1A1 in two Vietnamese sibling brothers with jaundice manifestations suspected GS. The peripheral blood samples of patients were used to extract genome DNA and sequence the enhancer, promoter, and coding all five exons of UGT1A1. Two pathogenic variants c.-3279T>G located in the phenobarbital responsive enhancer module (gtPBREM) and A(TA)7TAA of the TATA box in the promoter region were identified. They are twice common pathogenic variants that were reported in almost hyperbilirubinemia individuals from different populations. The obtained results improved the accuracy of medical diagnosis and warned the patients to be cautious in case they have to use medical drugs in the future.

Mechanism of bilirubin elimination in urine: insights and prospects for neonatal jaundice

Despite a century of research, bilirubin metabolism and the transport mechanisms responsible for homeostasis of bilirubin in serum remain controversial. Emerging evidence on the hepatic membrane transporters and inherited disorders of bilirubin metabolism have contributed to a greater understanding of the various steps involved in bilirubin homeostasis and its associated excretory pathways. We discuss these recent research findings on hepatic membrane transporters and evaluate their significance on the newborn bilirubin metabolism and excretion. New insights gained speculate that a proportion of conjugated bilirubin is excreted via the renal system, as an alternative to the intestinal excretion, even in normal physiological jaundice with no associated pathological concerns. Finally, this paper discusses the clinical relevance of targeting the altered renal excretory pathway, as bilirubin in urine may hold diagnostic importance in screening for neonatal jaundice.

Physiological and Hereditary Hyperbilirubinemia in Athletes: Role in Reducing Efficiency and Correction Methodology

Under high-intensity loads, the athlete's bodies take place a number of biochemical reactions and physiological processes that can lead to hyperbilirubinemia. The factors that can initiate the onset of this phenomenon include the syndrome of micro-damage muscle, violation of the integrity of erythrocyte membranes, decreased blood pH, malnutrition and increase oxygen demand of the body. Degree of expression of manifestations of physiological bilirubinemia depends on the level of adaptation of the athlete to the physical activities offered. Hyperbilirubinemia in athletes can be one of the components of the deterioration of the functional state, forming the symptoms of endogenous intoxication. The relevance of this problem in sport lies in the relatively low detection rate of hyperbilirubinemia due to the lack of regular screening studies. However, in drawing up a plan of nutritional- metabolic support for training and competitive activity and recovery measures, must not only the individual reaction of the athlete body to physical activity, but also the severity of shifts in the indicators of bilirubin metabolism and their ratio. The article describes the reasons for the increase in bilirubin levels, which can be caused by both the effect of physical activity and by the presence of pathological processes in athletes. The factors influencing the blood serum’s bilirubin content are also highlighted, which include the state of erythrocyte cell membranes and the rate of hemoglobin destruction, the functional state of the liver, the specifics of physical loads and the use of ergogenic pharmacological agents by athletes. Particular accent has been placed on the illumination of hereditary hyperbilirubinemias, which may have been detected at the stage of selection of athletes. The most common phenomenon is Gilbert's syndrome, which occurs in 2-5% of cases in the general population, is characterized in the clinic by a benign flow and is manifested by episodes of jaundice and an increase in total bilirubin content to moderate values due to indirect. The frequency of detection of hyperbilirubinemias in the population of athletes is 4.68%, among which Gilbert's disease accounts for almost half (48.7%). Conclusion. The work highlighted the pathogenesis and diagnostic algorithm of Gilbert's disease, and also emphasized that its drug prevention and correction in athletes to maintain functional and physical fitness should be carried out taking into account anti-doping rules, which requires upon diagnosis timely receipt of a therapeutic exclusion