Induction of Anti-inflammatory and Altered T-Cell Proliferative Responses by the Ethanol Root Extract of Plumbago zeylanica. in Adjuvant-Induced Arthritic Rats

ABSTRACT

The ethanol root extract of Plumbago zeylanica. L. (PZE) was investigated for anti-inflammatory activity in adjuvant-induced arthritic (AIA) rats. The AIA rats were treated with PZE (20 mg/kg body weight) daily from day 0 to day 13. The PZE reduced the paw thickness and paw volume of AIA rats. The effect of PZE treatment was assessed in cutaneous delayed type hypersensitivity (DTH) response to Mycobacterium. tuberculin (MT) in development of AIA. The results demonstrated that PZE inhibited the development of cutaneous DTH response in AIA rats. The T-cell proliferation induced by concanavalin A (Con A), a mitogen, was depressed in three different strains of AIA rats (Wistar, Lewis, and Fischer) when compared with that of normal; however, the PZE treatment of AIA rats reversed the decrease of T-cell proliferation to the normal levels. The treatment of AIA rats with PZE on splenic T-cell proliferation was also compared with T-cell proliferation of rats that were treated with the known anti-inflammatory compounds such as cyclophosphamide and indomethacin.     

Anti-α-galactoside and Anti-β-glucoside Antibodies are Partially Occupied by Either of Two Albumin-bound O-glycoproteins and Circulate as Ligand-binding Triplets

Two heavily O-glycosylated proteins and albumin co-purified with anti-α-galactoside (anti-Gal), the chief xenograft-rejecting antibody and anti-β-glucan (ABG) antibody isolated from human plasma by affinity chromatography on respective ligand-bearing matrices. Both antibodies and O-glycoproteins co-purified with plasma albumin eluted from albumin-specific matrix. Using components of affinity-purified antibody samples separated by electrophoresis binding of either albumin or antibody to the affinity matrix of the other or binding of O-glycoprotein to either matrix was ruled out. Enzyme-linked immunoassay and ligand-induced fluorescence enhancement of fluorolabeled antibody showed that O-glycoproteins occupied sugar-binding sites of anti-Gal and ABG. Neither antibody recognized albumin. O-Glycoprotein-albumin complexes free in plasma, or released from antibodies by specific sugars, were captured on microwell-coated O-glycan-specific lectin jacalin and detected using labeled anti-albumin. We conclude that circulating anti-Gal and ABG form protein triplets in which either O-glycoprotein bridges between antibody and albumin by binding simultaneously to both. Bound albumin restricted O-glycoprotein occupation on antibodies enabling triplets to bind other ligands using spared binding sites. Free anti-Gal and ABG were undetectable in plasma. Jacalin treatment, but not de-O-glycosylation of O-glycoproteins abolished their recognition by anti-Gal or ABG indicating that antibodies recognized serine- and threonine-rich peptide sequences that underlie the O-glycans and are reported surrogate ligands for anti-Gal. The albumin- and antibody-binding O-glycoproteins AOP1 and AOP2 were single polypeptide proteins of size 107 kDa and 98 kDa, containing 54% and 51% carbohydrate respectively and conformed to no known plasma protein in properties. Prospects of triplet-mediated modulations in autologous tissues expressing antibody ligands are discussed.     

Dietary lutein reduces ultraviolet radiation-induced inflammation and immunosuppression

Ultraviolet radiation (UVR) promotes skin cancer development by mutagenic, immunosuppressive, and oxidative-stress-inducing mechanisms; however, certain antioxidants may counteract and prevent UVR-induced photodamage. Lutein is a xanthophyll carotenoid with potent antioxidant activity. Because reactive oxygen species (ROS) are believed to have a role in UVR-induced skin damage, we investigated whether lutein can modify UVR effects including the tissue swelling response to midrange UVR (280-320 nm, ultraviolet B (UVB) radiation) and UVB suppression of contact hypersensitivity (CHS) in both the local and the systemic models of UV-induced immunosuppression. We found that compared to mice fed the standard laboratory diet, mice fed dietary lutein demonstrated significant inhibition of ear swelling owing to UVB radiation. Mice exposed to 1700 J per m2 UVB radiation four times at daily intervals and then sensitized to dinitrofluorobenzene at the site of irradiation showed a decreased CHS response upon challenge. This suppression by UVB radiation was significantly inhibited by lutein feeding. When UVB radiation was given at a single dose of 10,000 J per m2 to inhibit the induction of CHS at a distant, nonirradiated site, no effect of lutein was seen. Finally, lutein accumulated in the skin of mice following diet supplementation and was shown to decrease ROS generation following UVR exposure. Thus, lutein modulates the skin's response to UVR and may contribute to the defense against some of the deleterious effects of solar radiation.     

Permanent mandibular incisor with multiple anomalies - report of a rare clinical case

Permanent mandibular central incisor is rarely affected by tooth shape anomalies of crown and root. Co-occurrence of multiple anomalies in a permanent mandibular central incisor is extremely rare. This paper reports an unusual concurrent combination of multiple dental anomalies affecting both the crown and root of a permanent mandibular left central incisor - talon cusp, dens invaginatus, short root anomaly and macrodontia -, which has not previously been reported together. Case management is described and implications are discussed. The dentist should be aware of these rare entities in order to provide an accurate diagnosis and management for which detailed examination of the tooth both clinically and radiographically is very important.     

Differential modifying effects of food additive butylated hydroxytoluene toward radiation and 4-nitro-quinoline 1-oxide-induced genotoxicity in yeast

The modifying effect of butylated hydroxytoluene (BHT) on 60Co gamma radiation and 4-nitro-quinoline 1-oxide-induced gene conversion and back mutation frequencies was investigated using diploid yeast Saccharomyces cerevisiae D7. Cells were exposed to 100 or 400 Gy in the presence of 0.025-0.25 mM BHT. BHT exhibited radioprotection and significantly reduced radiation-induced gene conversion and back mutation frequencies as well as cell killing. In another set of experiments, cells were simultaneously treated with 0.025-0.1 mM BHT and 0.5 μM 4-NQO. BHT significantly enhanced 4-NQO-induced gene conversion and back mutation frequencies. BHT post-treatment did not modify radiation-induced genetic events but enhanced 4-NQO-induced back mutation frequencies, indicating its potential to act as a tumor-promoting agent with 4-NQO.     

A temporal study on the histopathological, biochemical and molecular responses of CCl(4)-induced hepatotoxicity in Cyp2e1-null mice

Previous study using Cyp2e1-null mice showed that Cyp2e1 is required in CCl(4)-induced liver injury at 24h, what remains unclear are the temporal changes in liver damage and the spectrum of genes involved in this process. We investigated the time-dependent liver changes that occurred at morphological, histopathological, biochemical and molecular levels in both Cyp2e1(+/+) and Cyp2e1(-/-) mice after treating with either corn oil or CCl(4) (1 ml/kg) for 2, 6, 12, 24 and 48 h. A pale orange colored liver, indicative of fatty infiltration, was observed in Cyp2e1(+/+) mice treated with CCl(4) for 24 and 48 h, while the Cyp2e1(+/+) mice treated with corn oil and Cyp2e1(-/-) mice treated with either corn oil or CCl(4) showed normal reddish brown colored liver. Ballooned hepatocytes with multiple vacuoles in their cytoplasm were observed in the livers of Cyp2e1(+/+) mice 24 and 48 h after treating with CCl(4). The levels of serum alanine aminotransferase and aspartate aminotransferase, markers for liver injury, were significantly higher at 12h, peaked at 24h and gradually decreased at 48 h after CCl(4) intoxication. In contrast, this kind of damage was not apparent in the Cyp2e1(-/-) mice treated with CCl(4). Altered expressions of genes related to liver cirrhosis, apoptosis, oxidative stress, xenobiotic detoxification, lipid metabolism, chemsensory signaling or tumorigenesis, structural organization, regeneration and inflammatory response were identified, and the time-dependent changes in expression of these genes were varied. Overall, the present study provides insights into the mechanism of CCl(4)-induced hepatotoxicity in animal models.     

Multi-lobed mesiodens with a palatal talon cusp: a rare case report

Mesiodens is a midline supernumerary tooth commonly seen in the maxillary arch and the talon cusp is a rare dental developmental anomaly seen on the lingual surface of anterior teeth. This paper presents a rare clinical case of development of talon cusp in a mesiodens with multiple lobes, which interfered with both occlusion and appearance of an 11-year-old patient. During clinical interview, the patient reported difficulty on mastication. Clinical and radiographic examination revealed that a supernumerary tooth with completely formed root was causing an occlusal interference. The supernumerary tooth was diagnosed as multi-lobed mesiodens associated with a palatal talon cusp. The treatment plan consisted in the extraction of the supernumerary tooth followed by orthodontic treatment for diastema closure and tooth alignment.