Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors.

BACKGROUND & AIMS There is an unclear relationship between inhibitory receptor expression on T cells and their ability to control viral infections. Studies of human immune cells have been mostly limited to T cells from blood, which is often not the site of infection. We investigated the relationship between T-cell location, expression of inhibitory receptors, maturation, and viral control using blood and liver T cells from patients with hepatitis C virus (HCV) and other viral infections. METHODS We analyzed 36 liver samples from HCV antibody-positive patients (30 from patients with chronic HCV infection, 5 from patients with sustained virological responses to treatment, and 1 from a patient with spontaneous clearance) with 19 paired blood samples and 51 liver samples from HCV-negative patients with 17 paired blood samples. Intrahepatic and circulating lymphocytes were extracted; T-cell markers and inhibitory receptors were quantified for total and virus-specific T cells by flow cytometry. RESULTS Levels of the markers PD-1 and 2B4 (but not CD160, TIM-3, or LAG-3) were increased on intrahepatic T cells from healthy and diseased liver tissues compared with T cells from blood. HCV-specific intrahepatic CD8(+) T cells from patients with chronic HCV infection were distinct in that they expressed TIM-3 along with PD-1 and 2B4. In comparison, HCV-specific CD8(+) T cells from patients with sustained virological responses and T cells that recognized cytomegalovirus lacked TIM-3 but expressed higher levels of LAG-3; these cells also had different memory phenotypes and proliferative capacity. CONCLUSIONS T cells from liver express different inhibitory receptors than T cells from blood, independent of liver disease. HCV-specific and cytomegalovirus-specific CD8(+) T cells can be differentiated based on their expression of inhibitory receptors; these correlate with their memory phenotype and levels of proliferation and viral control.
Susceptibility to praziquantel of male and female cercariae of praziquantel-resistant and susceptible isolates of Schistosoma mansoni

Abstract Praziquantel (PZQ) is now widely used for the treatment of human schistosomiasis. However, in recent years, there has been a growing concern about the resistance of Schistosoma to PZQ. The mechanisms of PZQ action against Schistosoma and resistance of Schistosoma to PZQ are poorly understood. Here, we report differential susceptibilities to PZQ between male and female cercariae in the PZQ-susceptible and PZQ-resistant isolates of Schistosoma mansoni, using tail loss as a measurement of PZQ action. The miracidia were collected by hatching eggs collected from faeces of infected mice. Single-sex cercaria lines were made by infecting a single Biomphalaria glabrata snail with a single miracidium. The sex of each single-sex cercaria line was identified by a direct W1-specific polymerase chain reaction (PCR) technique. Single-sex cercariae of two isolates were exposed to four different concentrations of PZQ, respectively. The tail shedding of cercariae was observed under a dissecting microscope for five time points up to 100 min after adding PZQ. The results showed that male cercariae have higher tail-shedding rates than that of female cercariae when PZQ-susceptible isolates of S. mansoni are exposed to the same concentration of PZQ. But this phenomenon was not observed in the PZQ-resistant isolates. This sexual differential resistance phenomenon of S. mansoni suggests that resistance to PZQ is induced by decreasing the PZQ susceptibility of male worms. The experiment described here may also be useful for developing tests to detect PZQ resistance in the field.
Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21.

BACKGROUND & AIMS The hepatocyte-derived hormone fibroblast growth factor 21 (FGF21) is a hormone-like regulator of metabolism. The nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 regulates fatty acid metabolism through multiple nutrient sensors. Hepatic overexpression of SIRT1 reduces steatosis and glucose intolerance in obese mice. We investigated mechanisms by which SIRT1 controls hepatic steatosis in mice. METHODS Liver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates (controls) were divided into groups that were placed on a normal chow diet, fasted for 24 hours, or fasted for 24 hours and then fed for 6 hours. Liver tissues were collected and analyzed by histologic examination, gene expression profiling, and real-time polymerase chain reaction assays. Human HepG2 cells were incubated with pharmacologic activators of SIRT1 (resveratrol or SRT1720) and mitochondrion oxidation consumption rate and immunoblot analyses were performed. FGF21 was overexpressed in SIRT1 LKO mice using an adenoviral vector. Energy expenditure was assessed by indirect calorimetry. RESULTS Prolonged fasting induced lipid deposition in livers of control mice, but severe hepatic steatosis in SIRT1 LKO mice. Gene expression analysis showed that fasting up-regulated FGF21 in livers of control mice but not in SIRT1 LKO mice. Decreased hepatic and circulating levels of FGF21 in fasted SIRT1 LKO mice were associated with reduced hepatic expression of genes involved in fatty acid oxidation and ketogenesis, and increased expression of genes that control lipogenesis, compared with fasted control mice. Resveratrol or SRT1720 each increased the transcriptional activity of the FGF21 promoter (-2070/+117) and levels of FGF21 messenger RNA and protein in HepG2 cells. Surprisingly, SIRT1 LKO mice developed late-onset obesity with impaired whole-body energy expenditure. Hepatic overexpression of FGF21 in SIRT1 LKO mice increased the expression of genes that regulate fatty acid oxidation, decreased fasting-induced steatosis, reduced obesity, increased energy expenditure, and promoted browning of white adipose tissue. CONCLUSIONS SIRT1-mediated activation of FGF21 prevents liver steatosis caused by fasting. This hepatocyte-derived endocrine signaling appears to regulate expression of genes that control a brown fat-like program in white adipose tissue, energy expenditure, and adiposity. Strategies to activate SIRT1 or FGF21 could be used to treat fatty liver disease and obesity.
Global burden of oral diseases: emerging concepts, management and interplay with systemic health.

OBJECTIVES This study presents the global burden of major oral diseases with an exegetical commentary on their current profiles, the critical issues in oral healthcare and future perspectives. METHODS A narrative overview of current literature was undertaken to synthesise the contexts with critical elaboration and commentary. RESULTS Oral disease is one of the most common public health issues worldwide with significant socio-economic impacts, and yet it is frequently neglected in public health policy. The oral data extracted from the Global Burden of Disease Study in 2010 (Murray et al, 2012) show that caries, periodontal disease, edentulism, oral cancer and cleft lip/palate collectively accounted for 18 814 000 disability-adjusted life-years; and the global burden of periodontal disease, oral cancer and caries increased markedly by an average of 45.6% from 1990 to 2010 in parallel with the major non-communicable diseases like diabetes by 69.0%. Oral diseases and non-communicable diseases are closely interlinked through sharing common risk factors (e.g. excess sugar consumption and tobacco use) and underlying infection/inflammatory pathways. CONCLUSIONS Oral disease remains a major public health burden worldwide. It is of great importance to integrate oral health into global health agenda via the common risk factor approach. The long-term sustainable strategy for global oral health should focus on health promotion and disease prevention through effective multidisciplinary teamwork.
HYPERTENSION IN TAKAYASU'S ARTERITIS: PP.38.493

Introduction and Purpose: Takayasu's arteritis is a rare chronic inflammatory disease, which normally affects the aorta and its main branches, and less often, the pulmonary arteries. Hypertension is common in Takayasu's arteritis and may be related to changes of vascular compliance, renal vascular ischaemia with hypereninaemia or increased sensitivity of the carotid body. The aim of our study was to determine the etiologic profile of hypertension in Takayasu's disease. Patients and Methods: We carried out a retrospective study of 7 cases of Takayasu's arteritis admitted to our department from January 1999 to April 2009. Diagnosis was established according to the classification criteria of the American College of Rheumatology (ACR) in 1990. Results: Seven women were studied; mean age at diagnosis was 34, 57 years. Classification criteria were abnormal arteriography in 100% of cases, diminished brachial pulses in 100%, vascular bruits in 85%, claudication of lower limbs in 57%, difference of blood pressure between arms (>10mmHg) in 57% and age <40 years in 85%. Mean clinical manifestations were malaise in 42%, syncope in 14%, acute cerebrovascular accident in 14%, arthralgia in 28% and visual disorders in 28% of cases. Hypertension was noted in 4 cases (57%). The mean age was 25.5 years (21 – 35 years). In the 4 cases arteriography was abnormal showing renal artery stenosis. Stenosis was bilateral in one case. In one case, the patient was admitted for malignant hypertension and the diagnosis of TA was making. All patients were treated with calcic blokers drugs in association with specific treatment. The chirurgical treatment was angioplasty of the left renal artery in one case and by-pass of the left renal artery in one case. Conclusion: The diagnosis and treatment of hypertension in this disease is imperative, as the commonest causes of death are congestive heart failure, myocardial infarction and strokes, while retinopathy and severe systemic hypertension are predictive of increased mortality.
Oral manifestations associated with human immunodeficiency virus infection in 200 Indian patients

Objective: To determine the pattern and prevalence of oral lesions in HIV infected 200 costal Andhra Pradesh patients. Patients and methods: the study population comprised 200 consecutive HIV seropositive patients presented to regional ART center at Andhra Pradesh, India. The oral lesions were diagnosed based on clinical appearance and were entered in to the database for analysis. Results: 30-39 yrs age group was most commonly affected and 87% of the patients had acquired infection via heterosexual contact. Oral lesions were seen in 66% of the patients. Gingivitis (36.7% males & 33.9% females) was the most common lesion followed by candidiasis (21% males & 26.4% females), periodontitis (6.8% males & 7.5% females), pigmentation (36.7% males & 33.9% females), ulcers (2.7% males & 0% females) and leukoplakia (1.3% males & 0% females). Conclusion: The pattern of oral lesions associated with HIV infection was not markedly different form those reported in the literature, the prevalence of each type of lesion differ slightly. Key words: CD4 lymphocyte count; Female; HIV infections; Male; Humans. DOI: 10.3329/bjms.v9i3. 6470 Bangladesh Journal of Medical Science Vol.09 No.3 July 2010, pp.150-153
Heterorhabditis atacamensis n. sp. (Nematoda: Heterorhabditidae), a new entomopathogenic nematode from the Atacama Desert, Chile

Abstract A new Heterorhabditis species of entomopathogenic nematode was isolated from soil of the Atacama Desert in Chile. The new species is characterized by morphometrics of the infective juvenile (IJ) with length (L) = 611 (578–666) μm, head to excretory pore length (EP) = 115 (101–126) μm, tail = 69 (62–79) μm long, (EP/tail) × 100 (E%) = 165 (149–182) and L/maximum body diameter (ratio a) = 28 (25–31). The male has spicules 45 (40–49) μm long, gubernaculum 20 (17–22) μm long and (spicule length/anal body diameter) × 100 (SW%) = 205 (179–249). The hermaphroditic adult has shallow cuticular folds immediately anterior and posterior to the vulva, a slight post-anal swelling and a finely rounded tail terminus. Morphologically, H. atacamensis n. sp. resembles H. safricana, H. marelatus, H. downesi and H. amazonensis, but can be distinguished by characters of adult and IJ stages. In particular, for adult males, H. atacamensis n. sp. differs from H. amazonensis by the number and orientation of the genital papillae and from H. downesi by the position of the excretory pore; by the shape of the female tail terminus from H. downesi and by the position of the IJ hemizonid from H. marelatus. Heterorhabditis atacamensis n. sp. is further characterized by internal transcribed spacer (ITS) and D2D3 rDNA sequences, the closest species, H. safricana, being separated by 13 bp across 730 bp of the ITS (incorporating ITS1 (partial sequence), 5.8S (complete sequence), ITS2 (complete sequence)) and 5 bp across 592 bp of the partial 28S (incorporating D2D3) sequence. The morphological and molecular data confirm that H. atacamensis n. sp. is a valid species.
In vitro assessment of praziquantel and a novel nanomaterial against protoscoleces of Echinococcus granulosus

Abstract The present study describes the activity of a nanomaterial on protoscoleces of Echinococcus granulosus, which exhibited morphological changes and apoptosis. Apoptotic changes were deduced on the basis of effector caspase activation and nucleosomal laddering. Invaginated protoscoleces maintained in vitro became evaginated and had hooks, presumptive suckers and stalks. Degenerative changes of protoscoleces were evidenced after treatment with praziquantel and nano-combination. Protoscoleces treated with praziquantel had distinct attestation of necrosis and nano-combination-treated protoscoleces had signatures of apoptosis.
Different techniques for management of common bile duct stones: a single centre experience.

Abstract Local experience on the combined technique of endoscopic sphincterotomy followed by endo: scopic balloon dilation is scarce. This study clarified whether this crombined technique will offer any advantages, with respect to therapeutic outcome and complications rate, as compared with endoscopic sphincterotomy (ES) and endoscopic balloon dilatation (EBD) alone for the extraction of large and/or multiple common bile duct stones. For a total of 76 patients, extraction of large and/or multiple common bile duct (CBD) stones during endoscopic retrograde cholangiopancreatography was performed. According to the used technique, they were categorized into 3 groups; Endoscopic sphincterotomy, endoscopic balloon dilatation or combined technique. The success rate of complete stone removal and the incidence of procedure-related complications were compared among the three groups. Success rate after one session was recorded to be comparable among the three groups. Relative Risk Ratio assessment of success rate after single session among the three groups showed no statistically significant difference. Regarding bleeding, only 3 (10%) cases were recorded in the ES group with no cases in the, other 2 groups. No significant difference was noted among the three groups regarding other complication. The combined technique of ES followed by EBD is an effective and safe technique enables extraction of multiple and/or relatively large stones. It could be a reasonable alternative option when standard techniques are inadequate to remove bile duct stones.
Levels of infection of gastric nematodes in a flock of great cormorants (Phalacrocorax carbo) from Lake Biwa, Japan

Abstract A high prevalence (86.7%) of various species of nematodes was observed in the stomach of great cormorants living in Lake Biwa, Japan. There were varying numbers of adults belonging to two common genera, Eustrongylides Jagerskiold 1909 (Nematoda: Dioctophymatidae) and Contracaecum Railliet & Henry 1912 (Nematoda: Anisakidae). The first included common adenophorean nematodes comprising a single species, Eustrongylides tubifex and the second comprised ascaroid nematodes that contained four named species: Contracaecum rudolphii Hartwich, 1964, Contracaecum microcephalum Yamaguti, 1961, Contracaecum multipapillatum Drasche, 1882 and Contracaecum chubutensis Garbin, 2008. After the prevalence and intensity of the infection had been noted, both types of nematodes were frequently observed to penetrate the mucosa and intrude into the wall of the glandular stomach, where they caused gross haemorrhage and ulceration. The Eustrongylides sp. was predominantly found in a nodular lesion of the proventricular wall, while Contracaecum spp. were observed either free in the lumen of the proventriculus or, on occasion, deeply penetrating its wall. Of the Contracaecum spp. , C. rudolphii was the most prevalent. Grossly, large numbers of nematodes were present in infected stomachs (for C. rudolphii intensity was 1–34 and 3–57 nematodes in male birds and 1–21 and 1–32 in females; for C. microcephalum 1–2 and 1 in male birds and 1–2 in females; for C. multipapillatum 2 in male cormorants and no infection in females; for C. chubutensis 1–2 and 1 in male birds and 1–5 and 1 in females and for E. tubifex 1–5 nematodes in male birds and 2–8 in females). Ulcerative inflammation and hyperaemia were the most common pathological presentations, especially in areas that had been invaded by parasites. Microscopically, varying degrees of granulomatous inflammatory reactions were seen, in addition to degenerated nematodes which appeared to have deeply penetrated mucosal surfaces and were surrounded by fibrous connective tissues.
Helicobacter pylori vaccines—the current status

In this review, we take a look at the current status in the development of a vaccine against the human pathogenic bacterium, Helicobacter pylori, a major aetiological factor in peptic ulcer disease and gastric adenocarcinoma. Various animal models are now in use from mice infected with H. pylori, through gnotobiotic pigs and primates to ferrets naturally infected with their own Helicobacter, H. mustelae. A significant problem remains the requirement for a suitable mucosal adjuvant. Detoxification or the use of low doses of adjuvants already available may provide a solution and new immune stimulating compounds have been tested with some success. New approaches include the delivery of Helicobacter antigens by DNA immunization, microparticles or live vectors such as attenuated salmonella and the examination of alternative routes of vaccine administration. The phenomenon of post‐immunization gastritis and improvements in vaccine efficacy are also discussed. A major area of interest is the mechanism by which immunization actually influences Helicobacter colonization. This remains a mystery: antibodies appear to be unimportant whereas CD4+ T‐cells essential. Finally, a viewpoint is given on whom should be immunized when a final vaccine becomes available.
Intracellular Hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice.

BACKGROUND & AIMS High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice after induction of acute pancreatitis. METHODS We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1(flox/flox) mice). Acute pancreatitis was induced in these mice (HMGB1(flox/flox) mice served as controls) after injection of l-arginine or cerulein. Pancreatic tissues and acinar cells were collected and analyzed by histologic, immunoblot, and immunohistochemical analyses. RESULTS After injection of l-arginine or cerulein, Pdx1-Cre; HMGB1(flox/flox) mice developed acute pancreatitis more rapidly than controls, with increased mortality. Pancreatic tissues of these mice also had higher levels of serum amylase, acinar cell death, leukocyte infiltration, and interstitial edema than controls. Pancreatic tissues and acinar cells collected from the Pdx1-Cre; HMGB1(flox/flox) mice after l-arginine or cerulein injection demonstrated nuclear catastrophe with greater nucleosome release when compared with controls, along with increased phosphorylation/activation of RELA nuclear factor κB, degradation of inhibitor of κB, and phosphorylation of mitogen-activated protein kinase. Inhibitors of reactive oxygen species (N-acetyl-l-cysteine) blocked l-arginine-induced DNA damage, necrosis, apoptosis, release of nucleosomes, and activation of nuclear factor κB in pancreatic tissues and acinar cells from Pdx1-Cre; HMGB1(flox/flox) and control mice. Exogenous genomic DNA and recombinant histone H3 proteins significantly induced release of HMGB1 from mouse macrophages; administration of antibodies against H3 to mice reduced serum levels of HMGB1 and increased survival after l-arginine injection. CONCLUSIONS In 2 mouse models of acute pancreatitis, intracellular HMGB1 appeared to prevent nuclear catastrophe and release of inflammatory nucleosomes to block inflammation. These findings indicate a role for the innate immune response in tissue damage.
Co-infections of the cestode Echinococcus vogeli and the nematode Calodium hepaticum in the hystricomorphic rodent Agouti paca from a forest reserve in Acre, Brazil

Abstract The helminth fauna of Agouti paca (Linnaeus, 1766) has seldom been studied. In this paper, we report an unusual mixed infection of Echinococcus vogeli Rausch & Bernstein, 1972 and Calodium hepaticum (syn. Capillaria hepatica Bancroft, 1863) in free-ranging paca from a forested region in Acre (Brazil). Gross morphological examination revealed that paca liver contained multiple spherical to subspherical white or translucent lesions, which were isolated or frequently contiguous and partially covered by Glisson's capsule. Microscopic examination revealed unilocular cystic structures that contained abundant brood capsules in which numerous protoscolices budded from the inner surface. The protoscolices possessed rostellar hooks (33–41 μm in length), a morphological characteristic of the blade and calcareous corpuscles that is consistent with the metacestode E. vogeli. The diagnosis of C. hepaticum infection was based on the morphology and morphometry of the egg-shaped ellipsoids with bipolar plugs (44.8 ± 1.9 μm (length) × 24.4 ± 2.0 μm (width)) and liver histopathology. This finding expands the known range of C. hepaticum hosts in South America and, to the best of our knowledge, it is the first case of a mixed infection of E. vogeli and C. hepaticum. Furthermore, our data provide evidence that wild animal meat may be a source of C. hepaticum infection.
Determination of role of ceruloplasmin in oral potentially malignant disorders and oral malignancy-A cross-sectional study.

OBJECTIVES In the process of carcinogenesis, lipid peroxidation and increased oxidative stress lead to changes in certain antioxidants. This study was aimed to assess and co-relate serum levels of ceruloplasmin in oral premalignancies and oral cancer so as to gauge its possible association with the process of carcinogenesis and to determine its role as tumor marker. MATERIAL AND METHODS The study population comprised of 300 participants, equally divided into six study groups, that is, oral submucous fibrosis (OSMF), oral leukoplakia (OL), nicotina stomatitis (NS), oral malignancy (OM), controls (C), and healthy controls (HC); 5 ml of blood was collected from ante cubital vein from each participant. The serum was analyzed for ceruloplasmin levels using ERBA CHEM 5 PLUS semiautomated chemistry analyzer and diagnostic kit by turbidimetric immunoassay. RESULTS There were total 242 males and 58 females, who were between 18 and 82 years of age, with a mean of 45.31 ± 13.97 years. The serum ceruloplasmin levels were significantly increased in OM, OSMF, OL, and NS groups as compared to C and HC groups (p < .001). No statistically significant difference was found in intragroup analysis of the disease groups (p > .05). CONCLUSION Serum ceruloplasmin can be used as diagnostic marker for oral premalignant and malignant lesions.