Grape seed protects cholestatic rats liver from ischemia/reperfusion injury

ABSTRACT PURPOSE: To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed. RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.

Cytotoxicity and hepatoprotective attributes of methanolic extract of Rumex vesicarius L

BACKGROUND: To evaluate the hepatoprotective potential and invitro cytotoxicity studies of whole plant methanol extract of Rumex vesicarius L. Methanol extract at a dose of 100 mg/kg bw and 200 mg/kg bw were assessed for its hepatoprotective potential against CCl4-induced hepatotoxicity by monitoring activity levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamic pyruvic transaminase), ALP (Alkaline phosphatase), TP (Total protein), TB (Total bilirubin) and SOD (Superoxide dismutase), CAT (Catalase), MDA (Malondialdehyde). The cytotoxicity of the same extract on HepG2 cell lines were also assessed using MTT assay method at the concentration of 62.5, 125, 250, 500 µg/ml. RESULTS: Pretreatment of animals with whole plant methanol extracts of Rumex vesicarius L. significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver. The biochemical parameters in serum also improved in treated groups compared to the control and standard (silymarin) groups. Histopathological investigation further corroborated these biochemical observations. The cytotoxicity results indicated that the plant extract which were inhibitory to the proliferation of HepG2 cell line with IC50 value of 563.33 ± 0.8 Mg/ml were not cytotoxic and appears to be safe. CONCLUSIONS: Rumex vesicarius L. whole plant methanol extract exhibit hepatoprotective activity. However the cytotoxicity in HepG2 is inexplicable and warrants further study.

Detection of Apical Inflammatory Root Resorption Associated with Periapical Lesion Using Different Methods

The aim of this study was to detect apical inflammatory root resorption (AIRR) associated with periapical lesion using cone beam computed tomography (CBCT) and scanning electronic microscopy (SEM). This clinical study evaluated AIRR in 88 root apexes, from 52 permanent teeth of 14 patients, extracted for different reasons. The patients were submitted to a clinical interview, review of dental/medical histories and clinical/imaging examinations for treatment planning. All selected teeth showed unrestorable condition because of the extensive coronal breakdown due to carious lesions, and root canal infection associated with periapical lesions. CBCT images were obtained from the patients with the aim of diagnosing the periapical diseases which showed complex or doubtful conditions. Two examiners assessed the presence or absence of AIRR. Apices were also analyzed under SEM. Chi-square test was used to compare the imaging methods for detection of AIRR. The level of statistical significance was set at 5%. AIRR associated with root canal infection and apical periodontitis was found in 61.4% of the cases studied by using SEM, and at least half of the cases by CBCT. The microscopic analysis remains as a reference standard against the imaging method to identify AIRR.

O objetivo deste estudo foi detectar reabsorção radicular inflamatória apical (RRIA) associada à lesão periapical utilizando tomografia computadorizada de feixe cônico (TCFC) e microscopia eletrônica de varredura (MEV). Este estudo clínico avaliou RRIA em 88 ápices radiculares de 52 dentes permanentes de 14 pacientes, extraídos por diferentes motivos. Os pacientes foram submetidos a uma entrevista clínica, revisão da história médica/dental, exames clínicos e de imagem para o plano de tratamento. Todos os dentes selecionados apresentaram condição não restaurável devido à extensa perda de estrutura dental associada a lesões cariosas, e infecção do canal radicular associada a lesões periapicais. TCFC foram obtidas dos pacientes com o objetivo de diagnosticar as alterações periapicais que se mostraram complexas ou duvidosas. Dois examinadores avaliaram a presença ou ausência de RRIA. Os ápices foram também analisados por MEV. O teste do qui-quadrado foi usado para comparar os métodos de detecção de RRIA. O nível de significância foi estabelecido em 5%. RRIA associada à infecção do canal radicular e periodontite apical foi encontrada em 61,4% dos casos estudados usando MEV, e pelo menos metade dos casos utilizando TCFC. A análise microscópica continua a ser o padrão frente a métodos de imagens para a identificação de RRIA.

Síntese e metabolismo da bilirrubina e fisiopatologia da hiperbilirrubinemia associados à Síndrome de Gilbert: revisão de literatura / Bilirubin synthesis and metabolism, and hyperbilirubinemia associated with Gilbert’s Syndrome: A review of the literature

A icterícia é sinal clínico comum a várias condições patológicas, podendo ser evidenciada em vários locais do organismo devido à grande capacidade de impregnação do pigmento biliar. A icterícia torna-se evidente quando a concentração plasmática encontra-se acima de 2,5 a 3,0 mg/dL. O presente trabalho retrata o metabolismo fisiológico dos pigmentos biliares concomitantemente com a síntese e metabolismo de bilirrubina, assim como processos fisiopatológicos causados pelo aumento da bilirrubina plasmática (hiperbilirrubinemia), como ocorre na síndrome de Gilbert, caracterizada pela deficiência enzimática, que se manifesta clinicamente como icterícia. Compreender os passos da formação e excreção da bilirrubina é fundamental para a compreensão das manifestações clínicas e que ocorrem na icterícia, facilitando o entendimento dos mecanismos fisiopatológicos da hiperbilirrubinemia, como ocorrem na síndrome de Gilbert.

Jaundice is a common clinical manifestation of several pathological conditions. It can be found in several parts of the body because of the high impregnation capacity of the bile pigment. Jaundice is evident when plasmatic concentration is higher than 2.5 ? 3.0 mg/dL. This paper describes the physiological metabolism of bile pigments concomitantly with bilirubin synthesis and metabolism, as well as the pathophysiological processes derived from increased plasmatic bilirubin (hyperbilirubinemia). This is a circumstance typical of the Gilbert?s syndrome, which causes enzymatic deficiency that is clinically manifested as jaundice. Knowledge of the steps of bilirubin formation and excretion is crucial to shed light into the clinical manifestations of jaundice and thus gain more understanding of the physiological mechanisms of hyperbilirubinema associated with Gilbert?s syndrome.

Níveis aumentados de bilirrubina estão associados com risco reduzido de doença pulmonar e mortalidade / Increased bilirubin levels are associated with reduced risk of lung disease and mortality

Níveis aumentados de bilirrubina (acima de 2,34 mg/dL para homens e 1,75 mg/dL para mulheres) estão associados com uma redução de risco de doença respiratória e mortalidade geral por todas as causas.

Correlacionando icterícia, resultados de exames laboratoriais e diagnósticos de doenças / Correlating jaundice, laboratory test results and diagnosis of diseases

Para descobrir quais as doenças que mais comumente cursam com a icterícia em pacientes internados no Hospital Universitário Antônio Pedro (HUAP) e correlacioná-las com marcadores bioquímicos foram utilizados dados extraídos de prontuários de pacientes internados durante os anos de 2005 a 2007. 0s dados foram analisados usando métodos estatísticos como qui-quadrado e teste Z. Utilizamos a análise das dosagens de aspartato-aminotrans ferase (AST), alanina-aminotransferase (ALT), fosfatase alcalina (FA), gama-glutamiltransferase (gama-GT), bilirrubina (Bb) total e suas frações direta e indireta. Os sinais e sintomas mais comuns na amostra estudada foram: dor abdominal, vômitos e colúria, que estão presentes em cerca de 60% das queixas dos pacientes estudados. Na população entre nove e 85 anos de idade, a análise sugere que AST e ALT nos chamam atenção para uma possível lesão hepática associada aos casos de icterícia. Enquanto que FA e GGT são marcadores de colestase. A bilirrubina direta tem média mais elevada no grupo de pacientes entre nove e 85 anos e a bilirrubina indireta atinge níveis maiores no grupo com até dois meses de vida. As dosagens bioquímicas são armas muito importantes na pesquisa etiológica dos casos de icterícia.

To find out which diseases most commonly lead to jaundice in hospitalized patients in HUAP and correlate them with biochemical markers. We used data from medical records of patients hospitalized during the years 2005 to 2007. The data were analyzed using statistical methods to test and chi-square-Z. We used the analysis of the strengths of AST, ALI, FA, GGT, Bb and its fractions total direct and indirect. The most common signs and symptoms in the sample studied were abdominal pain, vomiting and choluria that are present in about 60% of complaints from patients. In the population between nine and 85 years of age, the analysis suggests that AST and ALT in calling attention to a possible liver damage linked to cases of jaundice. While FA and gamma-GT are markers of cholestasis. The direct bilirubin is highest average in the group of patients between nine and 85 years and indirect bilirubin levels higher in the group with up to two months of life. The biochemical doses are very important weapons in the etiological research of cases of jaundice.

Predicting neonatal hyperbilirubinemia using first day serum bilirubin levels.

Objective. To determine the first day total serum bilirubin (TSB) value which will predict with reasonable accuracy, neonates likely to develop subsequent significant hyperbilirubinemia. Methods. Serum bilirubin was estimated for all enrolled cases within 18 to 30 hr of life by microcapillary. The babies were then followed up clinically by 2 observers for the appearance and progression of jaundice every 12 hr till discharge and then daily upto fifth day of life. TSB estimation was repeated if the clinical assessment of jaundice was more than 10 mg/dl by any observer using Kramers Rule. Hyerbilirubinemia was defined as TSB level ≥12 mg/dl between 24 to 48 hr of life ≥15 mg/dl between 48 to 72 hr of life and 17 mg/dl beyond 72 hours of life. Results. A total of 200 neonates were enrolled in the study. Of these, 24 neonates (i.e., 12%) developed hyperbilirubinemia. The mean first day TSB value in the neonates who subsequently developed hyperbilirubinemia was 7.716 mg/dl as compared to a value of 5.154 mg/dl in those who did not. The difference was significant (p=0.000). Using Receiver operating characteristic (ROC) curve analysis, a value of 6.4 mg/dl (first day TSB) was determined to have the best predictive ability for subsequent hyperbilirubinemia with a sensitivity of 87.5%, specificity of 80.11%, positive predictive value of 37.5% and a negative predictive value of 97.92%. Conclusion. First day TSB estimation can serve as a reliable screening test for neonates at risk for subsequent hyperbilirubinemia. Neonates with the first day TSB level of less than 6.4 mg/dl have minimum risk of subsequent hyperbilirubinemia.

Transcutaneous bilirubin levels in healthy term and late preterm indian neonates.

Objective. To provide normative data for transcutaneous bilirubin (TcB) measurements in healthy term and late-preterm Indian neonates during first 72 h of age using a multiwavelength reflectance transcutaneous bilimeter. Methods. TcB measurements were performed in healthy neonates (gestation 35 wk), in a well-baby ward, using a multiwavelength transcutaneous bilimeter (BiliCheck®, SpectRx Inc, Norcross, GA). Age-specific percentiles values for each 6- h epoch starting at 0 h of age were calculated and an age-specific TcB nomogram was developed using different percentile values. Diagnostic ability of each percentile curve for prediction of hyperbilirubinemia, defined as requirement of phototherapy, was calculated. Results. We performed 925 TcB measurements on 625 healthy newborn infants (gestation: 35 to 41 wk; age: 0 to 72 h; mean birth weight: 2808±437 g). TcB increased in a linear manner with maximum rate of rise observed during first 24 h of age (50th percentile: 0.22 mg/dL/h). 50th percentile curve of age-specific TcB nomogram had high negative predictive value (99.8%) and acceptable positive predictive value (16.4%) for prediction of hyperbilirubinemia. Conclusion: We provided age-specific nomogram of TcB for first 72 h of age in healthy term and late-preterm Indian neonates. Percentile curves and rate of rise in TcB may help in identification of neonates at low-risk of development of hyperbilirubinemia facilitating their safer discharge from the hospital. Diagnostic utility of this nomogram for predicting hyperbilirubinemia needs to be tested in a separate validation cohort.

Clinical factors influencing liver stiffness as measured by transient elastography (Fibroscan(R)) in patients with chronic liver disease / 대한간학회지

BACKGROUND/AIMS: Transient elastography as performed using the Fibroscan(R) is a useful noninvasive method for evaluating hepatic fibrosis. However, recent studies have found that liver stiffness measurement (LSM) values are inappropriately elevated in acute hepatitis or in the acute flare state of chronic hepatitis, suggesting that the LSM value obtained by the Fibroscan(R) is not a reliable marker for fibrosis. We retrospectively evaluated the clinical factors influencing the LSM value obtained using transient elastography as performed using the Fibroscan(R) in patients with chronic liver disease. METHODS: A total of 298 patients who were followed in Kungpook National University Hospital from November 2007 to May 2008 due to previously established liver cirrhosis or chronic liver disease were investigated using the Fibroscan(R), laboratory test, ultrasound, and/or abdominal computed tomography. RESULTS: The 298 patients were aged 47.8+/-12.9 years (mean+/-SD). The cut-off value for a diagnosis of liver cirrhosis was 12.5 kPa (as used in previous studies). Thirty-six patients (15%) and 202 patients (85%) with chronic liver disease without clinical manifestation of cirrhosis had LSMs of >12.5 kPa and <12.5 kPa, respectively. Multivariate analysis revealed that LSM values were unusually increased in patients with chronic liver disease who were older (P=0.007) or who had increased gamma gultamyltranspetidase (GGT) (P=0.022), decreased albumin (P=0.015), or increased total bilirubin (P=0.009). CONCLUSIONS: This study reveals that age, GGT, and albumin are clinical factors influencing LSM values. This reinforces the need to interpret LSM values in the context of a defined diagnosis, biochemical data, radiologic examination, and other clinical findings.

Role of bilirubin as antioxidant in neonatal jaundice and effect of ethanolic extract of sweet lime peel on experimentally induced jaundice in rat.

Bilirubin above a threshold level is toxic to human system and is excreted in urinary and through gastrointestinal tract. The role of bilirubin as antioxidant is debatable. This paper aims at elucidating the role of bilirubin as an antioxidant in neonatal jaundice patients. It is observed that bilirubin up to 6 mg/dl in blood acts as an antioxidant and above 12.5 mg/dl is strongly prooxidant. Phototherapy is the accepted therapeutic management of neonatal jaundice and has been shown to enhance the oxidative stress. Approaches have been taken to formulate a herbal medication which will reduce bilirubin level in the neonates without inducing additional damages. The ethanolic extract of sweet lime peel, administered orally at a dose of 72 microg is found to reduce the oxidative stress in erythrocytes of phenylhydrazine-induced jaundiced rats treated with phototherapy.

Effects of chichorium intybus on bilirubin.

OBJECTIVE: To evaluate the in vitro effects of chichorium intybus on bilirubin levels. METHODS: In this study the bilirubin levels in the serum of thirty neonates staying in the NICU and suffering from clinical jaundice was determined three times: first without any alterations, second after adding chichorium intybus extract and third after adding the same amount of distilled water. The results were compared using SPSS statistical software. RESULTS: Of the patients evaluated 76.7% were male and 23.3% were female. The average age was 7.35 days. The mean difference observed in unconjugated bilirubin levels in the specimens containing chichorium intybus extract was 3.84 +/- 2.38 mg/dl and in the ones containing distilled water was 2.85 +/- 2.00 mg/dl. The mean difference observed in conjugated bilirubin levels was 0.29 +/- 0.32 mg/dl in specimens containing distilled water and 0.35 +/- 0.26 in the ones containing chichorium intybus. In none of the cases the results were found to be significant. CONCLUSION: In this study chichorium intybus was found to have no significant in vitro effect on the bilirubin level reported by the laboratory. The in vivo effects of this herbal medicine must be evaluated more closely.

Transcutaneous bilirubin in predicting hyperbilirubinemia in term neonates.

OBJECTIVE: To assess the utility of 24 and 48 hours transcutaneous bilirubin (TcB) index for predicting subsequent significant hyperbilirubinemia in healthy term neonates. METHODS: TcB indices were obtained for healthy, breastfed, term AGA newborns at 24 +/- 2, 48 +/- 2 and subsequently at intervals of 24 hours. Neonates with illness, on treatment and positive Direct Coomb's test were excluded. Serum bilirubin levels were obtained whenever indicated. Neonates having serum bilirubin > or = 17 mg/dL were considered as significant hyperbilirubinemia. The 24 and 48 hour TcB indices, as risk predictors for such hyperbilirubinemia were determined. RESULTS: Study included 461 healthy term neonates. The mean birth weight was 2949 (+/- 390) gm and mean gestation of 38.6 (+/- 1.1) weeks. Eight one (17.6%) had significant hyperbilirubinemia. Of 461, 135 (29.3%) had TcB index. CONCLUSION: The 24 and 48 hour TcB indices are predictive for subsequent significant hyperbilirubinemia and can guide clinician in early discharge of healthy term newborns.

Late onset jaundice and urinary tract infection in neonates.

OBJECTIVE: To determine the prevalence and the associated parameters of urinary tract infection (UTI) in infants with late onset jaundice. METHODS: This prospective analytic study was conducted among 400 cases, selected by simple sampling from neonates with late onset jaundice admitted in two referral hospitals of Isfahan during a 9-month period. The information including the age, sex and feeding type, as well as the results of physical examination, treatment, radiology studies, etc were recorded. The etiology of jaundice was assessed by laboratory tests. Urine analysis and urine culture were performed for all subjects. XZ and t-test were used for analysis of the data in- SPSS software. RESULTS: Of the 400 icteric neonates, 147 (36.8%) were female and 253 (63.3%) were male; 23 (5.8%) were diagnosed to have UTI, 5 cases (1.3%) had G6PD deficiency, 19 (4.8%) had dysmorphic red blood cell and 3(0.75%) had ABO or RH incompatibility. The relation between the type of feeding, circumcision and UTI was significant (P< 0.05). Of the 23 neonates with UTI,4 cases (17. 39%) were found to have urogenital abnormality. CONCLUSION: UTI was found in 5.8% of infants with late onset jaundice. The study revealed significant association between breast feeding, circumcision and lower prevalence of UTI in icteric neonates. It is suggested that evaluation for UTI should be considered as a screening test in all cases of neonatal late onset jaundice.

Enfoque del Paciente Ictérico / Approach of the Ictérico Patient

La ictericia es una consulta frecuente en los servicios de urgencia y de consulta externa. El médico general de be estar capacitado para el adecuado diagnóstico de estos pacientes. Con este artículo se pretende dar una ilustración y una guía al médico general para enfocar adecuadamente al paciente ictérico de tal forma que rapidamente sepa qué examenes de laboratorio y de imagenología se requieren...

Neonatal surgical jaundice revisited.

Neonatal hyperbilirubinemia is a common problem in newborn nurseries and manifest clinically as jaundice. Nearly 25-50% of all newborns and a much higher percentage of premature babies develop hyperbilirubinemia. This is mostly physiological, but a small percentage of these babies have pathological jaundice, requiring detailed investigations and management. It is also absolutely essential to consider a possibility of extra-hepatic biliary atresia early, during management of a case of neonatal direct hyperbilirubinemia as early surgical intervention results in a better outcome in EHBA. This article aims to describe the diagnostic approach to neonatal hyperbilirubinemia with special emphasis on conditions requiring surgical intervention also it throws light on present status of EHBA in Indian circumstances.

Comparison of di-isopropyl iminodiacetic acid with methyl isobutyl isonitrile in the work-up of infants with prolonged jaundice

The study group comprised of 16 jaundiced children [mean age 3.16 months] with bilirubin levels of more than 8mg/dl. The clinical differential diagnosis included biliary atresia versus neonatal hepatitis. Informed consent was taken from all the parents. Parents were advised to omit the morning feed. All children were pretreated with phenobarbitone [5mg/ kg/day for 5 days] and imaged twice on two different days: first with Tc-99m-DISIDA and dose of 37MBq was injected intravenously. Liver images were obtained at 1, 2, 3 and 24 hours following injection. Then injection of Tc-99m-MIBI with a dose of 37MBq was injected intravenously. Anterior abdominal images with 350k counts were obtained at 10, 20, 30 and 40 minutes post injection and where appropriate delayed additional views were taken to optimize radionuclide intestinal transit. Two nuclear medicine physicians visually analyzed the scintigrams. On the basis of biliary-enteric kinetics the patients were subdivided into sub-groups: Group 1: Included 12 patients with no bowel activity with DISIDA scan but demonstrable bowel activity with MIBI liver scan with the appearance of central or peripheral abdominal activity. Group 2: Consisted of 4 patients with no bowel activity with both DISIDA and MIBI liver scans. Of the 4 patients 2 had biliary atresia confirmed at laparotomy whilst 2 children were lost to follow-up since the children had traveled from remote parts of the country

In vitro and in vivo Efficacy of New Blue Light Emitting Diode Phototherapy Compared to Conventional Halogen Quartz Phototherapy for Neonatal Jaundice

High intensity light emitting diodes (LEDs) are being studied as possible light sources for the phototherapy of neonatal jaundice, as they can emit high intensity light of narrow wavelength band in the blue region of the visible light spectrum corresponding to the spectrum of maximal bilirubin absorption. We developed a prototype blue gallium nitride LED phototherapy unit with high intensity, and compared its efficacy to commercially used halogen quartz phototherapy device by measuring both in vitro and in vivo bilirubin photodegradation. The prototype device with two focused arrays, each with 500 blue LEDs, generated greater irradiance than the conventional device tested. The LED device showed a significantly higher efficacy of bilirubin photodegradation than the conventional phototherapy in both in vitro experiment using microhematocrit tubes (44 +/-7% vs. 35 +/-2%) and in vivo experiment using Gunn rats (30 +/-9% vs. 16 +/-8%). We conclude that high intensity blue LED device was much more effective than conventional phototherapy of both in vitro and in vivo bilirubin photodegradation. Further studies will be necessary to prove its clinical efficacy.

Noninvasive transcutaneous bilirubin as a screening test to identify the need for serum bilirubin assessment.

Hyperbilirubinemia is a common problem in the newborn infant. It can progress to develop kernicterus unless intervention is initiated. Severity and decision for management are usually based on serum bilirubin (TsB) which needs blood sampling. Transcutaneous bilirubin measurement is a noninvasive technique and the result correlates closely with TsB. A new transcutaneous bilirubinometer, Minolta AirShields Jaundice Meter, JM103, has been introduced The objectives of this study were: 1) To evaluate the accuracy of transcutaneous bilirubin (TcB) measured by JM 103, when compared to TsB, used clinically in a hospital setting (Leica Unistat Bilirubinometer) and 2) To develop a cut-off point of TcB level which indicated the need for serum bilirubin assessment. Three hundred and eighty eight term and near-term newborn infants with 460 paired TcB-TsB specimens were studied from August to November 2003. Birth weight was 3117.57 +/- 424.82 grams. TsB ranged from 4 to 19.6 mg/dL (x 10.5, SD 2.46). The correlation coefficient between TcB and TsB was significant (r 0.8, p < 0.001). TcB showed a tendency to underestimate TsB, with mean difference of 0.7 mg/dL, SD 1.6 mg/dL, and 95% confidence interval 0.85 and 0.55 mg/dL. TcB values of 8, 9, 10, 12 mg/dL were chosen as cut-off points that indicated the need for blood sampling for TsB (corresponded to hour-specific levels of 10, 12, 13 and 15 mg/dL, respectively when phototherapy should be initiated). In conclusion, noninvasive TcB assessment demonstrates significant accuracy, compared to TsB. It can be used as a screening test to identify the need for blood sampling for serum bilirubin level.