Investigation of a neuronal nitric oxide synthase gene (NOS1) polymorphism in a multiple sclerosis population

Multiple Sclerosis (MS) is a chronic neurological disease characterized by demyelination associated with infiltrating white blood cells in the central nervous system (CNS). Nitric oxide synthases (NOS) are a family of enzymes that control the production of nitric oxide. It is possible that neuronal NOS could be involved in MS pathophysiology and hence the nNOS gene is a potential candidate for involvement in disease susceptibility. The aim of this study was to determine whether allelic variation at the nNOS gene locus is associated with MS in an Australian cohort. DNA samples obtained from a Caucasian Australian population affected with MS and an unaffected control population, matched for gender, age and ethnicity, were genotyped for a microsatellite polymorphism in the promoter region of the nNOS gene. Allele frequencies were compared using chi-squared based statistical analyses with significance tested by Monte Carlo simulation. Allelic analysis of MS cases and controls produced a chi-squared value of 5.63 with simulated P = 0.96 (OR(max) = 1.41, 95% CI: 0.926-2.15). Similarly, a Mann-Whitney U analysis gave a non-significant P-value of 0.377 for allele distribution. No differences in allele frequencies were observed for gender or clinical course subtype (P > 0.05). Statistical analysis indicated that there is no association of this nNOS variant and MS and hence the gene does not appear to play a genetically significant role in disease susceptibility.     

Lung cancer risk and red meat consumption among Iowa women

OBJECTIVE: Some epidemiologic studies suggest that diets high in total fat, saturated fat, or cholesterol are associated with increased risk of lung cancer. Others suggest that diets high in red meat consumption, particularly well-done red meat, are a lung cancer risk factor. In Iowa, we had the opportunity to investigate concurrently the role of meat intake and macronutrients in lung cancer etiology. METHODS: A population-based case-control study of both non-smoking and smoking women was conducted in Iowa. A 70-item food frequency questionnaire (FFQ) was completed by 360 cases and 574 frequency-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Multivariate models included age, education, pack-years of smoking, yellow-green vegetable intake, fruit/fruit juice intake, nutrient density calories, previous non-malignant lung disease, alcohol consumption and body mass index (BMI). RESULTS: When comparing the fifth (highest) to the first (lowest) quintile of consumption of total fat, saturated fat and cholesterol, we obtained odds ratios of 2.0 (1.3-3.1), 3.0 (1.9-4.7), and 2.0 (1.3-3.0) respectively. However, when red meat was entered into the model along with total fat, saturated fat or cholesterol, the excess risk for the macronutrients disappeared while an odds ratio of 3.3 (1.7-7.6) was obtained for red meat. The odds ratios for red meat consumption were similar among adenocarcinoma cases, OR=3.0 (1.1-7.9) and non-adenocarcinoma cases, OR=3.2 (1.3-8.3) and among life-time nonsmokers and ex-smokers OR=2.8 (1.4-5.4), and current smokers, OR=4.9 (1.1-22.3). Yellow-green vegetables were protective with an odds ratio of 0.4 (0.2-0.7). CONCLUSIONS: Consumption of red meat, was associated with an increased risk of lung cancer even after controlling for total fat, saturated fat, cholesterol, fruit, yellow-green vegetable consumption and smoking history, while yellow-green vegetables are associated with a decreased risk of lung cancer.     

Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations

Ethnopharmacological relevance

Coptidis Rhizoma (Huanglian) and its major component, berberine, have drawn extensive attention toward their antineoplastic effects in the recent years. The antineoplastic effects are related to the Chinese Medicine (CM) properties of Huangliang in treating diseases by removing damp-heat and purging fire and counteracting toxicity.

Aim of the review

To trace the long history of the traditional use of Huanglian from folk medicines, especially from Chinese medicine, to recent pharmacological studies of Huanglian and berberine, with an emphasis on their antineoplastic effects and the promise as novel antineoplastic agents.

Methods

A total of seven databases were extensively searched for literature research. The terms and keywords for searching included Huanglian, berberine, Coptis, Coptidis Rhizoma, anticancer, anti-invasion, antimatastasis and mechanism. The papers including ours with studies on anticancer and mechanism, pharmacology and toxicology of Huanglian and/or berberine were focused.

Results

In view of traditional use, the anticancer effects of Huanglian can be ascribed to its CM trait by removing damp-heat, fire and toxicity. From modern biomedical studies, anticancer effects have been demonstrated in both Huanglian and berberine. The underlying molecular mechanisms involve cell-cycle arrest, apoptosis induction and anti-inflammation. Berberine is an essential anticancer compound in Huanglian. In some studies, the use of Huanglian was shown to be more effective and beneficial than the use of berberine alone. The presence of other protoberberine-type alkaloids in Huanglian might give synergistic effects for the anticancer effects. Berberine also demonstrates effects of antiangiogenesis, anti-invasion and anti-metastasis in some cancer cell lines, however, more investigations are required to unravel the underlying mechanisms involved.

Conclusions

The modern evidences of treating cancer with Huanglian and berberine have a strong linkage with traditional concept and rules of using Huanglian in CM practice. As anticancer candidates with low toxicity, berberine and its altered structure, as well as Huanglian and its formulae, will attract scientists to pursue the potential anticancer effects and the mechanisms by using technologies of genomics, proteomics and other advanced approaches. On the other hand, relatively few in vivo studies have been conducted on anticancer effects of Huanglian and berberine. The clinical application of berberine or Huanglian as novel cancer therapeutic agents requires in vivo validations and further investigations of their anticancer mechanisms.     

Chemical radiculitis. A clinical, physiological and immunological study

Chemical radiculitis is an inflammatory condition of the nerve root due to the rupture of the annulus fibrosus and dissemination of disk fluid along the nerve root sheath. The inflammatory component of disk fluid is glycoprotein. The inflammation is a reaction to repeated injuries of the spinal column, as for example, in occupational lifting of heavy loads. Rupture of the annulus fibrosus and liberation of disk fluid into the tissues also evokes circulating antibody response and auto immune reaction. A high titer to glycoprotein at 3 weeks after an acute attack of back pain is evidence of the presence of a significant disk lesion. In selected cases immediate relief from pain occurs after administration of cortisone or a suitable cortisone-derivative. Prolonged rest may be contraindicated because of the risk of formation of radicular adhesions.     

Allotypes of Serum α2-Macroglobulin β-Lipoprotein and Immunoglobulins in the Domesticated Sheep (Ovis Aries)

Abstract. Antisera specific for allotypic markers carried by the serum α₂-macro-globulin, β-lipoprotein and IgGl and IgG2 were produced during cross-immunization experiments with sheep (Ovis aries). Two markers controlled by autosomal co-dominant genes, Ap ¹ and Ap ², were found on the α₂-macroglobulin; one marker controlled by an autosomal dominant Lp ¹ was found on the β-lipoprotein, two markers controlled by the autosomal codominants, Igl ¹ and Igl ², were found on the IgGl and one marker, controlled by Ig2 ¹ and linked to Igl ¹, was found on the IgG2. The immunoglobulin markers all occurred on the Fc fragments of the immunoglobulin molecules. There was no linkage between the Ap and Lp loci or between these and the immunoglobulin loci. A preliminary survey of the incidences of the markers in various flocks of sheep showed that the incidence of Lp ¹ and Igl ¹ was very much higher in Merinos than in the British breeds of sheep.     

No evidence for involvement of the human inducible nitric oxide synthase (iNOS) gene in susceptibility to typical migraine.

Migraine is a debilitating disorder affecting approximately 12% of Caucasian populations. The disease has a large genetic component, although at present the type and number of genes involved is unclear. Candidate gene studies may be useful strategies for identifying genes involved in complex diseases such as migraine, especially if the gene being examined contributes only a minor effect to the overall phenotype. Nitric oxide (NO) is emerging as a key molecule affecting the pain associated with migraine. Since NO synthase (NOS) enzymes catalyze the synthesis of NO, the genes that code for these enzymes are good candidates for migraine molecular genetic analysis. This study investigated the role of a functionally relevant bi-allelic tetranucleotide polymorphism located in the promoter region of the human inducible nitric oxide synthase (iNOS) gene in migraine etiology. A large group of migraine affected individuals (n = 261) were genotyped and compared with an age- and sex-matched group of unaffected controls (n = 252). Results of a chi-squared analysis indicated that allele distributions for both migraine cases and controls were not significantly different (chi2 = 1.93, P = 0.16). These findings offer no evidence for an allelic association of the tested iNOS polymorphism with the common forms of the disease and therefore do not support a role for this gene in migraine pathogenesis.     

Glycosphingolipid clustering and mast cell degranulation

It was shown using spin-labelled probes that challenge of sensitized rat peritoneal mast cells results in clustering of sphingolipids located in the outer leaflet of the plasma membrane bilayer. This clustering is partially inhibited by antiallergic drugs of the chromone type. It is hypothesized that the sphingolipid clustering may be involved in the Ca++ gate mechanism which is associated with anaphylactically-induced mast cell degranulation.