Oral cocaine produces dose-related hepatotoxicity in male mice.

Cocaine remains a widely abused substance. While most addicts take cocaine intranasally, a considerable number abuse cocaine by mouth. It has been assumed that after oral exposure cocaine is hydrolyzed in the stomach rendering it ineffective. This study investigated the effect of orally administered cocaine on liver function and integrity as well as its effect on liver and blood antioxidative enzymes. Male CF-1 mice were orally administered either 0, 5, 10 or 20 mg cocaine/kg body weight and sacrificed 24 h after the last treatment. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured as markers of liver injury. Blood and liver glutathione (GSH) levels were determined as well as the activities of glutathione peroxidase (GPx) and catalase (CAT). In addition, the activity of liver glutathione reductase (GRx) was also measured. The results demonstrated that oral cocaine caused hepatotoxicity in a dose dependent manner. Serum ALT and AST were elevated while blood GSH concentration decreased in all cocaine treated animals. In addition, there was a significant dose dependent decrease in the activities of GPx and CAT in blood and liver of cocaine treated animals. However, hepatic GSH content and GRx activity manifested a significant increase, particularly in the group, which received 20 mg/kg cocaine. This study is the first to demonstrate that cocaine-induced hepatotoxicity results following the oral route of administration.     

Foot-and-Mouth Disease Virus: Molecular Interplays with IFN Response and the Importance of the Model

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals with a significant socioeconomic impact. One of the issues related to this disease is the ability of its etiological agent, foot-and-mouth disease virus (FMDV), to persist in the organism of its hosts via underlying mechanisms that remain to be elucidated. The establishment of a virus–host equilibrium via protein–protein interactions could contribute to explaining these phenomena. FMDV has indeed developed numerous strategies to evade the immune response, especially the type I interferon response. Viral proteins target this innate antiviral response at different levels, ranging from blocking the detection of viral RNAs to inhibiting the expression of ISGs. The large diversity of impacts of these interactions must be considered in the light of the in vitro models that have been used to demonstrate them, some being sometimes far from biological systems. In this review, we have therefore listed the interactions between FMDV and the interferon response as exhaustively as possible, focusing on both their biological effect and the study models used.     

Juvenile Visual Callosal Axons in Kittens Display Origin-and Fate-related Morphology and Distribution of Arbors

In kittens, callosal axons originating either from medial area 17 (transient axons) or near the 17/18 border (mostly permanent axons) were labelled with anterogradely transported biocytin; they were reconstructed by computer from serial sections, and their morphologies compared at different ages. During the first and second postnatal weeks both sets of axons branched profusely in the white matter of the lateral gyrus and the number of branches increased with age. The most common type of axon ending was the growth cone; others may have been collapsing growth cones, branches in the process of elimination or early synaptic boutons. Axons from medial area 17 distributed over a broad territory, including the 17/18 border where callosal axons terminate in the adult cat, but without aiming specifically at any one area. The majority of axons and their branches terminated in the white matter or at the bottom of layer VI; exceptionally they extended further into the cortex. Most of the axons originating near the 17/18 border were different from those described above, and the difference increased with age. Although they also terminated profusely in the white matter of the lateral gyrus, most of the branches terminated near the contralateral 17/18 border; they frequently entered the grey matter up to the superficial layers and branched into it. During the third week, axons from medial area 17 were rarely found to extend beyond the corpus callosum, probably because they were in the process of being eliminated. In contrast, axons originating near the 17/18 border had increased their number of branches in the grey matter. In conclusion, during the first and second postnatal weeks axons grew and differentiated according to their origin, and this anticipated whether they would be maintained or eliminated. Neurotrophic signals, possibly from the white matter or the subplate, and growth-inhibiting signals from area 17 may be involved in this process.     

Pemphigus foliaceus antigen: characterization of a keratinocyte envelope associated pool and preparation of a soluble immunoreactive fragment

In both the endemic and sporadic forms of pemphigus foliaceus (PF), antiepidermal autoantibodies against desmoglein I are present. Desmoglein I is a highly insoluble 160-kD transmembrane glycoprotein of the desmosomal core. The detailed immunochemical characterization of the epitope(s) recognized by the PF autoantibodies is hampered by its large molecular weight and the insolubility of desmoglein I in nondenaturing buffers. This study was designed to identify alternative methods that could yield soluble immunoreactive PF antigen (Ag) from normal human epidermis. The presence of PF Ag in human epidermis and in its soluble or insoluble fractions was monitored by indirect immunofluorescence, immunoadsorption of PF sera, and immunoprecipitation of radiolabeled fractions. The PF Ag from trypsin-resistant, radiolabeled cell envelope preparations was cleaved by papain and immunoprecipitated by PF sera. A 50-kD peptide, isoelectric at pH 5.5-5.8, was immunoprecipitated by sera from all patients with endemic PF (n = 15) or idiopathic PF (n = 4), and by two of four pemphigus vulgaris sera, but by no control sera (n = 7). This study shows that a significant fraction of the PF Ag is insoluble, trypsin-resistant, and is associated with the cornified cell envelope fraction, but an Ag fragment can be obtained in a small molecular weight, soluble, and immunoreactive form by papain digestion. This 50-kD papain fragment is more amenable to detailed chemical and immunologic characterization than the native molecule.     

Post-traumatic diabetes insipidus combined with primary polydipsia

We describe a case of diabetes insipidus after head injury in which thirst persisted despite treatment with DDAVP and normal plasma osmolality. Symptoms were only completely relieved when plasma osmolality was below 270 mosmol/kg. We believe that this might have been due to hypothalamic injury causing resetting of the thirst osmostat. To our knowledge, this type of primary polydipsia has not been described before in association with diabetes insipidus following head injury.     

Growth of Callosal Terminal Arbors in Primary Visual Areas of the Cat

In kittens ranging in age between postnatal day (P) 5 and P150, callosal axons originating near the 17/18 border were anterogradely labelled with biocytin and reconstructed from serial sections. At the end of the first postnatal week most of the axons begin to invade the cortex near the 17/18 border with multiple branches; some axons already span the grey matter up to layer I. Branches tend to grow into the grey matter in loose bundles ≤l00 μm in diameter, separated by empty spaces of comparable width. In the following weeks additional branches are produced in the grey matter; this appears to blur the initial bundled distribution, although by the end of the first postnatal month the branches are distributed in discrete patches similar to the adult terminal columns. Although a few boutons (presumably synaptic boutons) are found in the white matter/subplate region at earlier ages, they appear in the grey matter from P12 onwards. Their number per axon increases with age, reaching adult values about the end of the first month. Subsequently the number of boutons continues to increase and remains above adult values at P50, P65 and P80; it then decreases, reaching adult levels by P150. During the first month boutons tend to be more numerous in the infragranular layers, but then the trend reverses in favour of the supragranular layers. In most cases, the distribution of boutons spares layer IV partially or completely. From the onset boutons are distributed in radial‘columns’whose diameter increases with age. They maintain selective laminar and columnar distributions through the period of rapid and exuberant increase. These distributions do not appear to be sharpened further by the reduction in the number of boutons to adult levels. On the whole, callosal terminal arbors differentiate through stages of exuberant, albeit progressively constrained, growth involving both progressive and regressive events. Comparisons with previous work suggest that visual activity might finely shape the arbor, from the onset of synaptogenesis onwards.     

Protective Role of <Emphasis Type="Italic">N</Emphasis>-Acetylcysteine on Isoprenaline-Induced Myocardial Injury: Histological,Immunohistochemical and Morphometric Study

Several researchers studied the protective effect of the N-acetylcysteine (NAC) when it was given before the induction of myocardial infarction (MI). Other researchers studied such protective effect when it was before done and after done of the MI. The missing data are the comparison between the protective effect of NAC before myocardial injury with its protective effect both before and after myocardial injury. The aim of the study was to compare the cardioprotective effect of NAC on the isoprenaline-induced myocardial injury before the isoprenaline (ISP) injection with its protective effect both before and after the ISP injection. This study was applied over both short and long time periods. A total of 90 male adult Wistar albino rats were used in the study. The rats were divided into four groups: control group, ISP-treated group, NAC-pretreated group and NAC-pre-& posttreated group. Based on the duration of the experiment, the second and third groups were further subdivided into a and b groups. Histological, immunohistochemical and histomorphometric analysis were used. The myocytes in the ISP-treated groups were fragmented, disrupted with karyolysis. The blood vessels were dilated, congested and associated with blood extravasation, interstitial edema and cellular inflammatory infiltration. Much improvement was observed in the NAC-pretreated group. Focal degeneration was detected in the muscle fibers. The capillaries were normal. Minimal blood extravasation and cellular infiltration were seen. The cardiac muscle fibers in the NAC-pre-& posttreated group were regularly arranged. The mean collagen fiber area percent of the ISP-treated groups was significantly higher by 8.3-folds and 10.1-folds as compared with that of the control group and was also higher by 5.5-folds and 6.8-folds as compared with that of the NAC-pre-&posttreated groups. The α-SMA area percent in the ISP-treated groups was significantly higher by 12.2-folds and 23.9-folds as compared with that of the control group and was higher by 7.5-folds and 15-folds as compared with that of the NAC-pre-& posttreated groups. The mean PCNA area percent of the ISP-treated groups was significantly higher by 126.2 and 164.8% as compared with that of the control group and was higher by 106.3 and 141.5% as compared with that of NAC-pre-& posttreated groups. ISP had deleterious effects on the heart. Administration of NAC before ISP injection could largely reduce the ISP-induced short- and long-term alterations. The protection was maximum with the use of NAC before the ISP injection and continued after the injection for 12 days.     

The optimal treatment of patients with mild and moderate acute cholecystitis: time for a revision of the Tokyo Guidelines

Introduction

According to the Tokyo Guidelines, severity of acute cholecystitis is divided into three grades based on the degree of inflammation and the presence of organ dysfunction. These guidelines recommend grade I (mild) acute cholecystitis to be treated with early laparoscopic cholecystectomy and grade II (moderate) acute cholecystitis with delayed cholecystectomy. Yet, several studies have shown that, for acute cholecystitis in general, early cholecystectomy is superior to delayed cholecystectomy in terms of complication rate, duration of hospital stay and costs. The aim of this study was to determine the clinical outcomes of emergency cholecystectomy in patients with grade II acute cholecystitis. Based on our findings, we propose a revision of the Tokyo Guidelines.

Methods

We performed a retrospective observational cohort study of 589 consecutive patients undergoing emergency cholecystectomy for acute calculous cholecystitis in a large teaching hospital between January 2002 and January 2015. Patients were classified according to the severity assessment criteria of the Tokyo Guidelines. Patients with grade I and grade II acute cholecystitis were compared for perioperative outcomes.

Results

Emergency cholecystectomy was performed in 270 patients with grade I acute cholecystitis and 187 patients with grade II acute cholecystitis. There was no difference in conversion rate (6 vs. 6%, p = 0.985) and operating time (60 min [25–255] vs. 70 min [30–255], p = 0.421). Also the perioperative complication rate (7 vs. 9%, p = 0.517), 30-day mortality (1 vs. 1%, p = 0.648) and length of hospital stay (4 days [1–42] vs. 4 days [1–62], p = 0.327) were similar between grade I and grade II acute cholecystitis.

Conclusion

The clinical outcomes of emergency cholecystectomy did not differ between patients with grade I and grade II acute cholecystitis. The findings support a revision of the Tokyo Guidelines with respect to the recommendation of performing emergency cholecystectomy in both grade I and grade II acute cholecystitis.