Flaxseed extract reduces tissue accumulation and enhances urinary excretion of chondroitin sulphate in the rat: a possible new path in substrate reduction therapy for mucopolysaccharidosis.

CONTEXT: Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs. OBJECTIVE: We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation. MATERIALS AND METHODS: The study was performed in adult male Wistar rats (n = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined. RESULTS: Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC50 = 8.37 ± 0.176), DPPH (IC50 = 12.79 ± 0.273)]. The LD50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group. DISCUSSION AND CONCLUSIONS: EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.

Ameliorative effect of Ononis natrix against chronic lead poisoning in mice: neurobehavioral, biochemical, and histological study.

Lead (Pb) is one of the most common heavy metals with toxicological effects on many tissues in humans as well as animals. In order to counteract the toxic effects of this metal, the administration of synthetic or natural antioxidants is thus required. The aim of this study was to examine the beneficial effect of the aqueous extract of Ononis natrix (AEON) against lead acetate-induced damage from a behavioral, biochemical, and histological point of view. Forty-eight male mice were divided into four equal groups: Ctr (control); Pb (lead acetate 1g/l); Pb + On 100 mg/kg (lead acetate 1 g/l + AEON 100 mg/kg); Pb + On 500 mg/kg (lead acetate 1 g/l + AEON 500 mg/kg). AEON was administered orally from day 21 after the start of lead exposure up to the end of the experiment. The results revealed that lead induced behavioral disorders, increased serum levels of liver markers (AST, ALT, and bilirubin), as well as kidney markers (urea and creatinine). At the same time, levels of thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) increased significantly. Moreover, Pb caused structural changes in the liver and kidneys of Pb-exposed mice. However, AEON administration significantly improved all lead-induced brain, liver, and kidney dysfunctions. Our results suggest that AEON could be a source of molecules with therapeutic potential against brain, liver, and kidney abnormalities caused by lead exposure.

Time dependent alteration of locomotor behavior in rat with acute liver failure induced cerebellar neuroinflammation and neuro-astroglial damage.

Hepatic encephalopathy (HE) is a neurophysiological syndrome secondary to acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar functional impairment. The aim of this study is to assess the time-dependent alteration of locomotor behavior and the glial and neuronal alteration in rat with acute HE induced chemically. The study was carried out in male Sprague-Dawley rats with thioacetamide (TAA) induced acute liver failure at different stages 12 h, 24 h and 36 h. Hepatic and renal functions were assessed via various biochemical and histopathological examinations, while the cerebellum and the midbrain were examined using histology and immunohistochemistry for tyrosine hydroxylase (TH), cyclooxygenase-2 (COX-2) and glial fibrillary acidic protein (GFAP). We used as well, the open field test and the Rotarod test for assessing the locomotor activity and coordination. Our data showed a progressive loss of liver function and a progressive alteration in locomotor behavior and motor coordination in acute HE rats. In the cerebellum, we noted an increase in the degeneration of cerebellar Purkinje neurons parallel to increased COX-2 immunoreactivity together with astrocytic morphology and density changes. Likewise, in substantia nigra pars compacta, TH levels were reduced. We showed through the current study, a progressive deterioration in locomotor behavior in acute HE rats, as a result of Purkinje neurons death and a deficient dopaminergic neurotransmission, together with the morpho-functional astroglial modifications involving the oxidative stress and neuroinflammation.

Linking Helicobacter pylori with gallbladder and biliary tract cancer in Moroccan population using clinical and pathological profiles.

It is of interest to assess the clinical and pathological aspects of Gallbladder and biliary tract carcinomas confirmed by histological data. It is also of further interest to evaluate the link between Helicobacter pylori and biliary tract cancers. Eighty-nine (89) cases (mean age 60±12 years) of Gallbladder and biliary tract cancer confirmed by histological data were enrolled for the study at the Department of Pathology in Mohammed VI University Hospital, in Morocco. The data such as age, sex, clinical and histo pathological features were collected. Bile duct specimens were investigated for H. pylori using Giemsa and immuno histo chemistry staining. Results show that bile duct stones were found in 53.9% of cases. It is known using histological data that adeno carcinoma is common accounting for 70 % of all bile duct tumors. Moreover, Helicobacter pylori was detected in 54% of cases linking with the presence of bile duct stones characterized by the histological subtype, the macroscopic classification and lymph node's presence (p<0.001). Thus, data collected suggest the potential association of Helicobacter pylori with gallbladder cancer possibly through the formation of bile duct stones.

Antidiabetic potential of Caralluma europaea against alloxan-induced diabetes in mice.

Medicinal plants play an important role in the management of diabetes mellitus especially in developing countries where resources are lacking. Herbal of natural origin, unlike the synthetic compounds, are more effective, safer and have less side effects. For continuing research on biological properties of Moroccan medicinal plants, the present work was undertaken to evaluate the potential and mechanism of the antidiabetic activity of the Caralluma europaea methanolic extract in alloxan-induced diabetic mice. A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phenolic compounds in the methanolic extract. The in vitro antioxidant property was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging method, reducing power and ß-carotene-linoleic acid assays. The acute toxicity of the extract was evaluated by giving it orally to mice at single doses of 200, 500, 1000, 2000 mg/kg body weight. The antidiabetic effect was conducted on Swiss albino mice. Diabetes was induced with single intraperitonial injection of alloxan monohydrate (200 mg/kg body weight) and animals were treated with methanol extract at a dose of 250 mg/kg and 500 mg/kg body weight. The blood glucose levels were measured and histopathological analysis of pancreas was performed to evaluate alloxan-induced tissue injuries. The main phenols identified and quantified in the extract were ferulic acid, quercetine, 3,4 dihydroxybenzoic acid, rutin, epigallocatechin, and catechin. Ferulic acid was found to be the main phenolic compound ant its proportion was up to 52% of total phenolic compounds, followed by quercetin (36%). The result showed that methanol extract exhibited an antioxidant effect. Acute toxicity studies revealed that C. europaea extract was safe up 2000 mg/kg body weight and approximate LD50 is more than 2000 mg/kg. Moreover, the methanol extract prevented the diabetogenic effect of alloxan and decreased significantly the blood glucose level (P < 0.001) in treated mice. Morphometric study of pancreas revealed that C. europaea extract protected significantly the islets of Langerhans against alloxan-induced tissue alterations.

Kinetic deterioration of short memory in rat with acute hepatic encephalopathy: Involvement of astroglial and neuronal dysfunctions.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from acute or chronic hepatic impairments. The clinical features of HE include attention as well as a mild cognitive deficits associated with impaired attentional and executive networks in patients as well as in animal models of HE. The underlining pathomechanism of memory impairment in HE patients is still not fully understood; however, it may involve a possible gliopathy as well as neuropathy. The aim of the present investigation is to assess progression of short working memory deterioration in acute HE and to delineate the glial and the neuronal alteration which may underlie such cognitive impairment. The study was carried out in male Sprague-Dawley rats with acute liver failure induced by thioacetamide (TAA). The study was performed on different stages of acute HE; 12 h, 24 h and 36 h following administration of TAA. The liver functions were assessed via different biochemical markers (ALT, AST, bilirubin, urea and creatinine) and an histopathological examination of the liver tissue. While for the behavioral study, we used T-Maze test to assess short working memory using the percentage of alternation behavior, together with an immunohistochemical analysis of the Glial Fibrillary Acidic Protein (GFAP) as the key marker of astrocytes in the hippocampus, as well as serotonin (5-HT) for 5-HTergic neurons within the dorsal Raphe nucleus (DRN). Our data revealed a progressive loss of liver tissue integrity with inflammation and hepatocytes degeneration which was associated to obvious loss of the liver function. In parallel, we observed a gradual alteration of the alternation behavior, as a sign of altered short working memory in the acute HE rats. At the central level, the immunohistochemical study showed a time dependent region-specific changes of GFAP-immunoreactive astrocytes within the hippocampus. While within the DRN, serotonin levels declined progressively in a time-dependant manner. Our data revealed for the first time, a gradual loss of short memory function in acute HE, resulting from liver dysfunction. Such cognitive deterioration may involve a possible gliopathy as well as a 5-HTergic dysfunction which could be considered as a new key element for understanding the basis of memory and attention loss in HE patients.

[Central neurocytomas: clinical and radiopathological correlations: about 12 cases]. / Neurocytomes centraux: corrélations cliniques et radiopathologiques à propos de 12 observations.

Central neurocytomas are defined as neoplasms composed of round, uniform cells, with neural immunophenotypic profile and low proliferation index. They account for 0.5% of intracranial tumors. They usually occur near the foramen of Monro and can cause obstructive hydrocephaly. We conducted a retrospective data collection from records of 12 patients with central neurocytomas in the Anatomopathological Laboratory at the Mohammed VI University Hospital, Marrakech, between January 2006 and June 2015. This study aimed to report and describe the radiopathological features of this rare histologic type. The male/female sex-ratio was 1.4. The average age at diagnosis was 22.3 years. The revealing symptomatology was dominated by intracranial hypertension associated with decreased visual acuity and diplopia in all patients. Our study concerned about simple biopsy in one case, subtotal resection in seven cases and total resection in four cases. Histopathological examination showed tumor proliferation with endocrine architecture. Tumor cells are more often small and uniform. Mitotic index was low. Tumor proliferation was associated with fibrillary fundus and vascular network with three types of trees. Immunohistochemical examination was identical in all patients. It showed tumor cells positive for anti-synaptophysin antibodies, chromogranine and NSE. In all patients the radio-pathologic correlation suggested central neurocytoma (grade II - WHO 2016). This study highlights the anatomo-clinical, radiological and evolutionary features of these rare tumors.