Protection by Ziziphora clinopoides of acetic acid-induced toxic bowel inflammation through reduction of cellular lipid peroxidation and myeloperoxidase activity

Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune, genetic and environmental factors. We were interested in examining the effect of a total extract from Ziziphora clinopoides, an Iranian folk herbal medicine, in the prevention and control of experimental mouse IBD. Z. clinopoides was administered (75, 150, 300 mg/kg) through drinking water to mice, which dispensed a toxic dose of acetic acid intrarectally. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic and microscopic examinations of the colon were performed. Biochemical evaluation of the inflamed colon was carried out using assays of myeloperoxidase (MPO) activity and thiobarbituric acid reacting substances (TBARS) as indicators of free radical activity and cellular lipid peroxidation. Results indicated that the activity of MPO and lipid peroxidation products (TBARS) increased in acetic acid-treated groups, while recovered by pretreatment of animals with Z. clinopoides (75-300 mg/kg) and prednisolone. All doses of Z. clinopoides and prednisolone-treated groups showed significant lower score values of macroscopic and microscopic characters when compared to the acetic acid-treated group. The beneficial effect of Z. clinopoides (300 mg/kg) was comparable to that of prednisolone. It is concluded that Z. clinopoides inhibits acetic acid toxic reactions in the mouse bowel through inhibition of cellular oxidative stress. Proper clinical investigation should be carried out to confirm the same activity in human.     

Different amino acid substitutions at the same position in rhodopsin lead to distinct phenotypes

PURPOSE: Identification of a novel rhodopsin mutation in a family with retinitis pigmentosa and comparison of the clinical phenotype to a known mutation at the same amino acid position. METHODS: Screening for mutations in rhodopsin was performed in 78 patients with retinitis pigmentosa. All exons and flanking intronic regions were amplified by PCR, sequenced, and compared to the reference sequence derived from the National Center for Biotechnology Information (NCBI, Bethesda, MD) database. Patients were characterized clinically according to the results of best corrected visual acuity testing (BCVA), slit lamp examination (SLE), funduscopy, Goldmann perimetry (GP), dark adaptometry (DA), and electroretinography (ERG). Structural analyses of the rhodopsin protein were performed with the Swiss-Pdb Viewer program available on-line (http://www.expasy.org.spdvbv/ provided in the public domain by Swiss Institute of Bioinformatics, Geneva, Switzerland). RESULTS: A novel rhodopsin mutation (Gly90Val) was identified in a Swiss family of three generations. The pedigree indicated autosomal dominant inheritance. No additional mutation was found in this family in other autosomal dominant genes. The BCVA of affected family members ranged from 20/25 to 20/20. Fundus examination showed fine pigment mottling in patients of the third generation and well-defined bone spicules in patients of the second generation. GP showed concentric constriction. DA demonstrated monophasic cone adaptation only. ERG revealed severely reduced rod and cone signals. The clinical picture is compatible with retinitis pigmentosa. A previously reported amino acid substitution at the same position in rhodopsin leads to a phenotype resembling night blindness in mutation carriers, whereas patients reported in the current study showed the classic retinitis pigmentosa phenotype. The effect of different amino acid substitutions on the three-dimensional structure of rhodopsin was analyzed by homology modeling. Distinct distortions of position 90 (shifts in amino acids 112 and 113) and additional hydrogen bonds were found. CONCLUSIONS: Different amino acid substitutions at position 90 of rhodopsin can lead to night blindness or retinitis pigmentosa. The data suggest that the property of the substituted amino acid distinguishes between the phenotypes.     

Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

AIM: To analyze the phenotype and function of dendritic cells (DC) from patients with hepatocellular carcinoma (HCC) in order to understand their role in this disease. METHODS: Myeloid dendritic cells were enumerated in peripheral blood of HCC patients. CD80, CD83, CD86 and HLA-DR expression on naive and stimulated myeloid dendritic cells from peripheral blood were analyzed. Myeloid dendritic cells were isolated from peripheral blood and their function was tested. Phagocytosis was analyzed using FITC-dextran beads, peptide specific stimulation, the capacity to stimulate allogeneic T cells and secretion of cytokines upon poly dI:dC was tested. RESULTS: Myeloid dendritic cells were reduced in patients with HCC. No differences in CD80, CD83, CD86 and HLA-DR expression were found on naive and stimulated myeloid dendritic cells from HCC patients and healthy controls. Normal phagocytosis or stimulation of peptide specific T cells was observed in contrast to an impaired allo-stimulatory capacity and a reduced IL-12 secretion. CONCLUSION: Impaired IL-12 production of mDCs in patients could lead to an impaired stimulatory capacity of naive T cells suggesting that IL-12 directed therapies may enhance tumor specific immune responses in HCC patients.     

S100A9 a new marker for monocytic human myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that negatively regulate the immune response during tumour progression, inflammation and infection. Only limited data are available on human MDSC because of the lack of specific markers. We have identified members of the S100 protein family-S100A8, S100A9 and S100A12 - specifically expressed in CD14(+) HLA-DR(-/low) MDSC. S100A9 staining in combination with anti-CD14 could be used to identify MDSC in whole blood from patients with colon cancer. An increase in the population of CD14(+) S100A9(high) MDSC was observed in the peripheral blood from colon cancer patients in comparison with healthy controls. Finally, nitric oxide synthase expression, a hallmark of MDSC, was induced in CD14(+) S100A9(high) upon lipopolysaccharide/interferon-γ stimulation. We propose S100 proteins as useful markers for the analysis and further characterization of human MDSC.     

Timing the early treatment of Class II,division 1 malocclusion — Clinical and research considerations

The aim of this study was to evaluate the correlation between timing of emergence of the permanent teeth and sagittal occlusal changes in children enrolled in a prospective clinical trial of Class II, division 1 treatment. The children, ages 7.2–13.3 years, met strict inclusion criteria and were assigned at random to treatment with either a headgear or a Fränkel functional appliance. Relationships between maxillary and mandibular first molars and canines, as well as overjet, were measured with digital calipers on casts made every 2 months and mounted on a SAM II articulator. The emergence of a permanent tooth was scored on a scale from 1 to 3, depending on the eruptive level of the tooth from cutting through the gingiva (1) to reaching the occlusal table (3). Specifically, emergence of the second premolars (PM2) and permanent second molars (M2), the most adjacent teeth to the first molars, was evaluated as it interacted with the development of the sagittal occlusion. Treatment of the distocclusion was as effective in late childhood as in mid-childhood. Within each appliance group, the emergence of PM2 and M2 did not affect the amount of progress toward Class I significantly (p> 0.05), indicating that improvement from distocclusion to neutrocclusion with each appliance is not influenced by the timing of emergence of these teeth. Although these findings support a one-phase treatment starting in the late mixed dentition, earlier intervention in mid-childhood may be required in the presence of several developmental conditions, or when the dental and skeletal development deviate significantly in the individual patient.     

Effect of intrauterine morphine sulfate exposure on cerebellar histomorphological changes in neonatal mice

Neurotoxic effects of morphine sulfate in adult cerebellar cortex and neonatal cerebral cortex have been studied in animal models. This study was done to determine the neurotoxic effects of prenatal morphine exposure on the histo-morphological changes of cerebellar cortical layer and Purkinje cells in mice neonates. In this experimental study 30 female mice were randomly allocated into cases and controls. In the case group, animals received morphine sulfate 10 mg/kg/body weight intraperitoneally for 7 days. After mating, dams received morphine sulfate 10 mg/kg/body weight intraperitoneally for 20 days of gestation. Animals in the control group received normal saline. On the day of delivery (P0), the cerebella of six neonates for each group were removed and stained with cresyl violet. Quantitative computer-assisted morphometric study was done on the cortical layer of the cerebellum. Morphine exposure caused a non-significant increase in fetal weight in the case group. Purkinje cells in cases were decreased in comparison with controls (p < 0.05). Histomorphometric examination revealed that the thickness of Purkinje and internal granular layers of the cerebellar cortex decreased in the morphine-exposed group (p < 0.05). This study revealed that morphine administration before and during pregnancy can cause Purkinje cell loss and reduction of thickness of the Purkinje and internal granular layer of the cerebellar cortex and size of Purkinje cells in neonatal mice.     

Timing the early treatment of Class II, division 1 malocclusion--clinical and research considerations.

The aim of this study was to evaluate the correlation between timing of emergence of the permanent teeth and sagittal occlusal changes in children enrolled in a prospective clinical trial of Class II, division 1 treatment. The children, ages 7.2-13.3 years, met strict inclusion criteria and were assigned at random to treatment with either a headgear or a Fr?nkel functional appliance. Relationships between maxillary and mandibular first molars and canines, as well as overjet, were measured with digital calipers on casts made every 2 months and mounted on a SAM II articulator. The emergence of a permanent tooth was scored on a scale from 1 to 3, depending on the eruptive level of the tooth from cutting through the gingiva (1) to reaching the occlusal table (3). Specifically, emergence of the second premolars (PM2) and permanent second molars (M2), the most adjacent teeth to the first molars, was evaluated as it interacted with the development of the sagittal occlusion. Treatment of the distocclusion was as effective in late childhood as in mid-childhood. Within each appliance group, the emergence of PM2 and M2 did not affect the amount of progress toward Class I significantly (p > 0.05), indicating that improvement from distocclusion to neutrocclusion with each appliance is not influenced by the timing of emergence of these teeth. Although these findings support a one-phase treatment starting in the late mixed dentition, earlier intervention in mid-childhood may be required in the presence of several developmental conditions, or when the dental and skeletal development deviate significantly in the individual patient.