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The purpose of this study was to quantify the proanthocyanidin content of pecan (Carya illinoinensis) pericarp extract (PPE) and to assess its useful impacts against carbon tetrachloride (CCl4)-induced hepatotoxicity. Rats were randomly divided into four groups: Group 1: received intraperitoneal injection of saline solution, Group 2: was injected with PPE (25 mg/kg body weight) for 10 consecutive days, Group 3: received CCl4 (0.5 ml/kg, subcutaneous injection), Group 4: was coadministred with PPE + CCl4. The CCl4 was administered every 3 days during 10 days. Results revealed the presence of a high amount of total proanthocyanidins in the PPE (81.01 ± 0.21 mg TAE.g−1DW). CCl4 injection induced significant reductions in hepatic antioxidants but increased hepatic lipid peroxidation (LPO) as well as serum injury biomarkers. However, cotreatment with PPE significantly (P

Hepatocellular carcinoma (HCC) is a serious threat to human health that has attracted substantial interest. The purpose of this study was to investigate the modulatory effect of bee honey against induced HCC by diethylnitrosamine/carbon tetrachloride (DEN/CCl4) in rats. HCC was induced by a single intraperitoneal dose of DEN (200 mg/kg B.W). Two weeks later, CCl4 (1 ml/kg) was intraperitoneally injected (three times a week). Bee honey was administered orally at 2 g/rat before and after the induction of HCC. The results showed that bee honey administration significantly increased body weight, decreased liver weight, and relative liver weight compared to those in the HCC-induced group. Moreover, a significant decrease in serum alpha-fetoprotein (AFP) as well as AST, ALT, GGT, ALP activities were observed in bee honey administration rats compared with those in HCC-induced group. Also, the hepatic MDA was significantly decreased; in addition, SOD, CAT, and GPx activities were significantly increased in groups treated with bee honey compared with those in the HCC group. The hepatic histopathology alterations caused by DEN/CCl4 injection were ameliorated by bee honey treatment. Likewise, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-β1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), glypican (GP-3), thioredoxin (TRX), and glutaredoxin (GRX) were downregulated, and caspase-3 was upregulated by bee honey treatment compared with untreated HCC-induced group. In conclusion, bee honey has remarkable beneficial effects against HCC induced in rats through its antioxidant, anti-inflammatory, antifibrotic, and antimetastatic effects. Practical Applications The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl4 exhibited inhibitory and ameliorative effects against DEN/CCl4-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey’s effects against DEN/CCl4-induced HCC in rats.

Colic remains a key health concern for horse owners and is one of the most common causes of death in managed horse populations.1 Intensive treatment for colic is required in 24 per cent of horses with colic seen in a primary care setting in the UK, and approximately half of these horses will undergo surgery.2 Since the 1970s, when colic surgery started to become more commonplace, advances in anaesthetic and surgical techniques, development of new pharmacological agents and improved postoperative care have led to significant increases in survival rates and reductions in postoperative morbidities.3 Colic surgery is now commonly performed in many equine referral hospitals and, for horses that stand following colic surgery, 74 to 85 per cent will survive to hospital discharge. Of these surviving horses, 63 to 85 per cent will return to their previous level of athletic performance.4 It can be difficult for first-opinion veterinary surgeons and horse owners to make decisions about the referral of a colic case and to estimate the likely costs of treatment – taking into account whether the horse is insured for treatment of colic. One of the challenges is that ‘colic’ is not a single disease but is a clinical sign of any one of 80 different conditions that can have different aetiologies and may or may not be treatable medically or surgically. Therefore, the likely treatment options, costs and prognosis can be difficult to predict in a first-opinion, non-hospital setting. Horse owners’ decision making regarding colic is also complex,5 and the …

Patients with Fanconi anemia (FA) often have birth defects that suggest the diagnosis of VATER association. A review of 2,245 cases of FA reported in the literature from 1927 to 2012 identified 108 cases with at least 3 of the defining features of VATER association; only 29 had been so noted by the authors. The FA VATER signature was the significantly higher frequency of renal and limb (radial and/or thumb) anomalies (93% of cases had both) compared with less than 30% of VATER patients; the presence of one or both of these birth defects should lead to testing for FA. The relative frequencies of the genotypes of the patients with FA VATER were strikingly different from those expected from the general FA population; only 19% were FANCA, while 21% were FANCB, 14% FANCD1/BRCA2, and 12% FANCD2. Consistent with their genotypes, those with the FA VATER phenotype had a worse prognosis than FA patients with milder phenotypes, with shorter median survival and earlier onset of malignancies. The early identification of FA patients among infants with VATER association should lead to earlier more proactive management, such as cancer surveillance and genetic counseling.

Objectives: To clarify the dynamics of molecules composing the blood–nerve barrier (BNB) in inflammatory neuropathies. Methods: The expression of four tight junction (TJ) proteins—claudin-1, claudin-5, occludin, and ZO-1—was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Results: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined. Conclusions: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB.

Hepcidin is the central regulator of systemic iron homeostasis. Dysregulation of hepcidin production results in a variety of iron disorders. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemias, and hepatitis C. Hepcidin excess is associated with anemia of inflammation, chronic kidney disease and iron-refractory iron deficiency anemia. Diagnostic and therapeutic applications of this new knowledge are beginning to emerge. Dr. Ernest Beutler played a significant role in advancing our understanding of the function of hepcidin. This review is dedicated to his memory.

There is increasing interest in the endoscopic treatment of Barrett’s esophagus. Endoscopic treatment has been utilized for many years, but in the past, no specific method has emerged as an appealing treatment option with appropriate safety, efficacy and ease of treatment for both patients and physicians. Recently there has been a growing literature related to the endoscopic ablation of Barrett’s esophagus using radiofrequency ablation (RFA) (Halo® system). In order to discuss when RFA is indicated for Barrett’s, one needs to know: (1) What is the ‘histology’ of the Barrett’s? Does the patient have intestinal metaplasia, low-grade dysplasia, high-grade dysplasia or intramucosal carcinoma? (2) What are the endoscopic options to be considered as opposed to RFA? What are the advantages and disadvantages of each? (3) What additional variables need to be examined?

Background: Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. No systematic study of the effect of gluten-free diet on gluten ataxia has ever been undertaken. Objective: To study the effect of gluten-free diet on patients presenting with ataxia caused by gluten sensitivity. Methods: 43 patients with gluten ataxia were studied. All were offered a gluten-free diet and monitored every six months. All patients underwent a battery of tests to assess their ataxia at baseline and after one year on diet. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. Fourteen patients refused the diet (control group). Three patients had persistently raised antigliadin antibodies despite adherence to the diet and were therefore excluded from the analysis. Results: After one year there was improvement in ataxia reflected in all of the ataxia tests in the treatment group. This was significant when compared with the control group. The diet associated improvement was apparent irrespective of the presence of an enteropathy. Conclusions: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy. The diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia.

Gastrointestinal (GI) function is complex and physiological measurements are subject to a variety of technical difficulties and practical limitations. The ideal technique would be non-invasive, widely available, convenient, and reliable and would not expose the subject to ionising radiation. It would permit direct assessment of GI function in the postprandial as well as the resting state, and be able to differentiate between food, secretion, and air in the lumen. GI structure and function are interdependent and the ideal technique would permit simultaneous assessment of these factors. Finally, the bowel operates as a functional whole and assessment of the GI tract proximal and distal to the area of interest is desirable. In this article the authors summarise the development and validation of magnetic resonance imaging techniques that overcome many of the deficiencies of existing methods, and have many characteristics of the "ideal" investigation of GI function.

To define the effects of Lee Silverman Voice Treatment (LSVT on swallowing and voice in eight patients with idiopathic Parkinson's disease.Each patient received a modified barium swallow (MBS) in addition to voice recording before and after 1 month of LSVT. Swallowing motility disorders were defined and temporal measures of the swallow were completed from the MBS. Voice evaluation included measures of vocal intensity, fundamental frequency, and the patient's perception of speech change.before LSVT, the most prevalent swallowing motility disorders were oral phase problems including reduced tongue control and strength. Reduced tongue base retraction resulting in residue in the vallecula was the most common disorder in the pharyngeal stage of the swallow. Oral transit time (OTT) and pharyngeal transit time (PTT) were prolonged. After LSVT, there was an overall 51% reduction in the number of swallowing motility disorders. Some temporal measures of swallowing were also significantly reduced as was the approximate amount of oral residue after 3 ml and 5 ml liquid swallows. Voice changes after LSVT included a significant increase in vocal intensity during sustained vowel phonation as well as during reading.LSVT seemingly improved neuromuscular control of the entire upper aerodigestive tract, improving oral tongue and tongue base function during the oral and pharyngeal phases of swallowing as well as improving vocal intensity.

Several biomarkers are currently used to determine chronic exposure of fish to environmental contaminants. In studies to assess the effects of pulp mill effluent on winter flounder (Pleuronectes americanus), body and hepatosomatic indices (HSIs), histopathology, levels of hepatic detoxifying enzymes, mixed function oxygenases (MFO), muscle acetylcholinesterase (Ache) and selected parasite abundance were compared in samples taken near a paper mill (sulphite-bleaching) and a number of reference sites. Our studies revealed a number of significant (P0.05) differences between samples taken near the paper mill and reference sites. Flounder captured at two locations near the mill were greater in length and weight, had elevated HSIs and more lesions in the liver and spleen while an acanthocephalan, Echinorhynchus gadi, located in the digestive tract, was lower than at more distant sites. Activity of MFO and Ache were similar at most sites and might be a reflection of the fish's foraging behaviour and consequently intermingling of populations from different locations during summer. These results support the view that several biomarkers should be utilised when assessing the health of fish living in habitats degraded by pollutants.

Study objective: To quantitatively assess cocaine liberation from various body packet materials. Design: 100-milligram cocaine packets (plastic bags with various wrapping techniques, paper, and condoms) were placed in a simulated gastric medium. Samples were also tested in an alkalinized gastric medium, with determination of both cocaine and benzoylecgonine concentrations using high-performance liquid chromatography with ultraviolet detection. Results: Cocaine liberation was greatest in acid medium, with increasing liberation from condom packets to cellophane bags (three wrapping techniques used) to paper packets. The same trend was noted in alkaline medium but with a far lower maximum cocaine concentration accompanied by rapid hydrolysis to its inactive metabolite, benzoylecgonine. Conclusion: Cocaine liberation of a known quantity of drug is dependent on the wrapping method and material used; thus, a good history from the "body-stuffer" is essential to predict potential cocaine liberation and toxicity. Rapid hydrolysis of cocaine to its inactive metabolite in an alkaline medium implies a role for gastric alkalinization in the acute management of these patients.

IN previous experiments1 the 0.02 M phosphate buffer of pH 6.8 was used for electrophoresis of bile pigments on paper. Under these conditions (in the absence of proteins) the conjugated bilirubin migrating anodically separates from the unconjugated bilirubin which remains on the starting line. The presence of bile salts clearly influences this separation. Purified preparations2 of conjugated bilirubin which are devoid of bile salts migrate in the form of a tail beginning just from the starting line. If bile salts are present a sharply denned zone of conjugated bilirubin separates, migrating in front of the bile salts. The velocity of migration of this zone in the presence of bile salts is considerably higher than the rate of migration of pure preparations of the pigment.