The ideal endpoint of hepatitis B virus (HBV) antiviral therapy is HBsAg loss, a difficult goal to obtain, especially in HBeAg negative patients. Herein, we report the results obtained by the addition of peg-interferon α-2a to a long-lasting nucleos(t)ide analogue therapy in a HBeAg negative, genotype D patient with steadily HBV-DNA negative/HBsAg positive values. In 2002, our Caucasian 44-year-old male patient received lamivudine and, 4 years later, added adefovir because of a virological breakthrough. In 2011, considering his young age, liver stiffness (4.3 kPa) and HBsAg levels (3533 IU/mL), we added Peg-interferon α-2a for six months (3 in combination with nucleos(t)ide analogues followed by 3 mo of Peg-interferon α-2a monotherapy). A decrease of HBsAg levels was observed after 1 mo (1.21 log) of Peg-interferon and 3 mo (1.88 log) after the discontinuation of all drugs. Later, a complete clearance of HBsAg was obtained with steadily undetectable HBV-DNA serum levels (< 9 IU/mL). HBsAg clearance by the addition of a short course of Peg-interferon α-2a represents an important result with clinical and pharmaco-economic implications, considering that nucleos(t)ide analogues therapy in HBeAg negative chronic hepatitis B patients is considered a long-lasting/life-long treatment. 相似文献
Central pancreatectomy (CP) is a parenchyma-sparing surgical procedure. The aims are to clarify the history and the development of CP and to give credits to those from whom it came. Ehrhardt, in 1908, described segmental neck resection (SNR) followed, in 1910, by Finney without reconstructive part. In 1950 Honjyo described two cases of SNR combined with gastrectomy for gastric cancer infiltrating the neck of the pancreas. Guillemin and Bessot (1957) and Letton and Wilson (1959) dealt only with the reconstructive aspect of CP. Dagradi and Serio, in 1982, performed the first CP including the resective and reconstructive aspects. Subsequently Iacono has validated it with functional endocrine and exocrine tests and popularized it worldwide. In 2003, Baca and Bokan performed laparoscopic CP and, In 2004, Giulianotti et al performed a robotic assisted CP. CP is performed worldwide either by open surgery or by using minimally-invasive or robotic approaches. This confirms that the operation does not belong to whom introduced it but to everyone who carries out it; however credit must be given to those from whom it came. 相似文献
The presence of pesticides has recently been reported in shrimp farms adjacent to agricultural areas on the east coast of the Gulf of California. This study assessed the possible effect of organophosphorus pesticides in the coastal environment of Sinaloa, México, using the white shrimp Litopenaeus vannamei as a bioindicator since their presence, abundance or behavior indicate some process or state of the system in which they live. Sublethal bioassays were performed on shrimps in intermolt state using commercial brands of organophosphorus pesticides, chlorpyrifos (0.0015 mg l−1), diazinon (0.0120 mg l−1), methamidophos (1.207 mg l−1), azinphos-methyl (0.0101 mg l−1), and methyl parathion (0.0075 mg l−1) were tested. Results showed reductions in glycogen, triglycerides, and total protein concentrations in shrimp muscle, except for the diazinon treatments, in which an increase in triglyceride level was detected. The observed alterations in the three cellular components were probably due to the metabolic compensation mechanism of the shrimp in reaction to the stress produced by organophosphorus pesticides, which act as endocrine disruptors. The establishment of continuous environmental monitoring programs of the coastal zone of Northwestern Mexico is strongly recommended.
The orexins A (oxA) and B are peptides discovered in the rat hypothalamus and successively found in some peripheral organs of the mammalian body. They binds two protein G-coupled receptors defined receptor 1 (ox1r) and 2 for orexins, the first of which is highly specific for oxA while the second binds both the peptides with equal affinity. This work aimed to detect the presence of oxA and ox1r in the testis of the South American camelid alpaca (Vicugna pacos) and investigate the role played by them on Leydig cell steroidogenesis. The species alpaca acquired, in the last years, increasing zootechnical interest for the quality of the wool produced and its breeding spread from the country of origin to USA, Australia and Europe. Immunohistochemistry allowed us to detect oxA in Leydig and Sertoli cells, spermatogonia, resting spermatocytes, round and oval spermatids. Ox1r-immunoreactivity was found in Leydig cells and round, oval and elongated spermatids. The expression of the two peptides in tissue extracts was established by using Western blotting technique. Such results demonstrated that in the alpaca testis exists in a cellular complex able to produce and/or internalize oxA. Finally, the effect of oxA on steroidogenesis was investigated by means of in vitro cultured thin testis slices which were added with oxA or/and Müllerian Inhibiting Substance (MIS), a steroidolitic agent basally produced by the Sertoli cell. OxA evoked increase of testosterone production while MIS a decrease. The consecutive addition of oxA and MIS, or vice versa, highlighted an antagonistic interplay between the two substances which has been thought to be the main molecular event at the basis of the oxA-stimulated steroidogenesis mechanism. 相似文献
Background.?Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. Methods.?HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180?μg/d) plus either RBV standard dosing (1000 or 1200?mg/d if <75 or ≥75?kg, respectively) or RBV induction (2000?mg/d) along with subcutaneous erythropoietin β (450?IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. Results.?A total of 357 patients received ≥1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14?μg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3?mg/dL; P?.005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P?=?.004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P?=?.007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P?=?.03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P?.001) as predictors of SVR. Conclusions.?A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV. 相似文献
Human malignant pleural mesothelioma (MPM) is considered a rare tumor, but recent estimations indicate that one-quarter million people will die of this neoplasm in Europe in the next three decades. The mineral asbestos is considered the main causative agent of this neoplasm. MPM is largely unresponsive to conventional chemotherapy/radiotherapy. In addition to asbestos exposure, genetic predisposition to asbestos carcinogenesis and to simian virus (SV)40 infection has also been suggested. SV40 is a DNA tumor virus found in some studies to be associated at high prevalence with MPM. SV40 sequences have also been detected, although at a lower prevalence than in MPM, in blood specimens from healthy donors. However, some studies have failed to reveal SV40 footprints in MPM and its association with this neoplasm. These conflicting results indicate the need for further investigations with new approaches. We report on the presence of antibodies in serum samples from patients affected by MPM that specifically react with two different SV40 mimotopes. The two SV40 peptides used in indirect ELISAs correspond to viral capsid proteins. ELISA with the two SV40 mimotopes gave overlapping results. Our data indicate that in serum samples from MPM-affected patients (n = 97), the prevalence of antibodies against SV40 viral capsid protein antigens is significantly higher (26%, P = 0.043) than in the control group (15%) represented by healthy subjects (n = 168) with the same median age (66 y) and sex. Our results suggest that SV40 is associated with a subset of MPM and circulates in humans. 相似文献
Regional odontodysplasia is a rare and significant dental malformation. It is a dental alteration of unknown etiology, involving both mesodermal and ectodermal dental components, which present clinical, radiographic, and histologic features. This article reports a clinical case of a 10-month-old child who was diagnosed with regional odontodysplasia in the maxilla, confirmed by radiographic examination, with a follow-up of 5 years. The clinical, radiographic, and histologic features were reviewed. 相似文献