Subchronic toxicity and genotoxicity studies of Hericium erinaceus ß-glucan extract preparation.

The medicinal effects of Hericium erinaceus have been long documented in scientific studies of Eastern traditional medicine. It is widely consumed, because of its nutritional qualities and perceived health benefits. Also, it is rich in ß-glucans, which has been shown to have immunomodulating and antitumor effects. The objective of the present study was to investigate adverse effects, if any, of ß-glucan extract preparation from H. erinaceus in subchronic toxicity and genotoxicity studies. The conduct of these studies was in compliance with Good Laboratory Practice (GLP) and test guidelines established by the Organization for Economic Cooperation and Development (OECD). In the subchronic toxicity study, Sprague Dawley rats (12/sex/group) were administered (gavage) H. erinaceus ß-glucan extract preparation at dose levels of 0, 500, 1000 and 2000 mg/kg body weight (bw)/day for 90 days. Treatment with H. erinaceus ß-glucan extract preparation did not result in any toxicologically significant treatment-related changes in clinical observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. Clinical pathology including hematology, serum chemistry, urinalysisand terminal necropsy (gross or histopathology findings) did not reveal any treatment-related adverse effects. The results of genotoxicity studies as evaluated by gene mutations in Salmonella typhimurium, in vitro chromosome aberrations and in vivo micronucleus test in mice did not reveal any genotoxicity of H. erinaceus ß-glucan extract preparation. Based on the subchronic study, the no observed-adverse-effect level (NOAEL) for H. erinaceus ß-glucan extract preparation was determined as 2000 mg/kg bw/day, the highest dose tested.

Call for Systematic Population-Based Cervical Cancer Screening: Findings from Community-Based Screening Camps in Tamil Nadu, India.

BACKGROUND: In India, systematic cervical cancer screening under the national programme is yet to cover the entire population and therefore opportunistic or camp based approach is commonly practiced screening mode currently. This study presents the proportion of screen-positive women [positive visual inspection of the cervix with acetic acid (VIA) and/or Papanicolaou (Pap) smear results] and its associated factors from a rural community-based cervical cancer screening conducted in a service setting. METHODS: In this cross-sectional study involving record review, data was drawn from free screening camps conducted by a non-governmental organization in two rural districts of Tamil Nadu, India between March 2015 and March 2017. The associations were assessed using adjusted prevalence ratio with 95% confidence interval. RESULTS: A total of 5,207 women were screened from 307 camps. The mean age was 39.5 years (SD: 8.6). At least one symptom was observed among 2,245 women (43.1%). Of 5,207 women, 19.4% (n=1,009, 95% CI: 18.3%, 20.5%) were screen-positive. Screen positivity in women.

An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract.

A toxicity/toxicokinetic swine-adapted infant formula feeding study was conducted in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive days during the preweaning period at carrageenan concentrations of 0, 300, 1000 and 2250 ppm under GLP guidelines. This study extends the observations in newborn baboons (McGill et al., 1977) to piglets and evaluates additional parameters: organ weights, clinical chemistry, special gastrointestinal tract stains (toluidine blue, Periodic Acid-Schiff), plasma levels of carrageenan; and evaluation of potential immune system effects. Using validated methods, immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood cytokine evaluations (IL-6, IL-8, IL1ß, TNF-α), and immunohistochemical staining of the gut for IL-8 and TNF-α were conducted. No treatment-related adverse effects at any carrageenan concentration were found on any parameter. Glucosuria in a few animals was not considered treatment-related. The high dose in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of exposure for human infants, as affirmed by JECFA and supports the safe use of carrageenan for infants ages 0-12 weeks and older and infants with special medical needs.

Bacterial mutagenicity screening in the pharmaceutical industry.

Genetic toxicity testing is used as an early surrogate for carcinogenicity testing. Genetic toxicity testing is also required by regulatory agencies to be conducted prior to initiation of first in human clinical trials and subsequent marketing for most small molecule pharmaceutical compounds. To reduce the chances of advancing mutagenic pharmaceutical candidates through the drug discovery and development processes, companies have focused on developing testing strategies to maximize hazard identification while minimizing resource expenditure due to late stage attrition. With a large number of testing options, consensus has not been reached on the best mutagenicity platform to use or on the best time to use a specific test to aid in the selection of drug candidates for development. Most companies use a process in which compounds are initially screened for mutagenicity early in drug development using tests that require only a few milligrams of compound and then follow those studies up with a more robust mutagenicity test prior to selecting a compound for full development. This review summarizes the current applications of bacterial mutagenicity assays utilized by pharmaceutical companies in early and late discovery programs. The initial impetus for this review was derived from a workshop on bacterial mutagenicity screening in the pharmaceutical industry presented at the 40th Annual Environmental Mutagen Society Meeting held in St. Louis, MO in October, 2009. However, included in this review are succinct summaries of use and interpretation of genetic toxicity assays, several mutagenicity assays that were not presented at the meeting, and updates to testing strategies resulting in current state-of the art description of best practices. In addition, here we discuss the advantages and liabilities of many broadly used mutagenicity screening platforms and strategies used by pharmaceutical companies. The sensitivity and specificity of these early mutagenicity screening assays using proprietary compounds and their concordance (predictivity) with the regulatory bacterial mutation test are discussed.

Neural tube defects in Pondicherry.

OBJECTIVE: This study was carried out to identify the trend and the frequency of neural tube defects from July 1998 to June 2004. METHODS: A total of 310 babies were born with neural tube defects with the overall frequency of 5.7/1000 births compared to 2.3/1000 births observed earlier in our hospital. RESULTS: The most common defect was spina bifida (54.8%) followed by anencephaly (31.6%), and encephalocele (11.6%). More neural tube defects were observed in female and low birth weight babies, still births and unbooked mothers. Neural tube defect was significantly higher among babies born to parents of consanguineous marriage (p< 0.01). Associated congenital defects were observed in thirty nine (12.6%) cases. CONCLUSION: The rise in the frequency of NTDS may indicate the current trend of NTDs in Southern India. A further prospective study is desired to measure the effectiveness of regular folic acid supplementation in bringing down this frequency.

Tuberculin reactivity in tuberculous meningitis.

OBJECTIVE: To study tuberculin reactivity in childhood tuberculous meningitis both in clinical and histopathological (HP) context. METHODOLOGY: Children with tuberculous meningitis (TBM) were given tuberculin test by Mantoux technique, which was read at the end of 72 hours after the placement of skin test. Histopathological examination of the punch biopsy specimen of the tuberculin test site was performed and histopathological grading of the tuberculin reaction was compared with clinical reaction and clinical parameters. RESULTS: Of the 50 children studied, 68% of them were malnourished and 42% had BCG scar. Tuberculin test was positive in 22 (44%) cases. Spearman analysis showed negative correlation between stage of TBM and the size of tuberculin reaction. BCG status did not affect the size of tuberculin reaction. Histopathological grade of the tuberculin reaction was found to be directly proportional to the size of the tuberculin reaction and it was not affected by the stage of TBM. CONCLUSION: Tuberculin positivity is low in TBM irrespective of the nutritional status. At least some degree of inflammatory reaction can be seen at the site of tuberculin administration. In tuberculin negative cases, varying grades of cellular response in the absence of clinical induration can be seen in histopathology.

Effects of the (-)-anti-11R,12S-dihydrodiol 13S,14R-epoxide of dibenzo.

The tumor suppressor protein p53 plays an important role in recognition of DNA damage and induction of subsequent cell cycle arrest. One of its target genes encodes the protein p21(WAF1), which is involved in mediation of growth arrest after DNA damage has occurred. Dibenzo[a,l]pyrene (DB[a,l]P) is a polycyclic aromatic hydrocarbon which is an exceptionally potent carcinogen. A reactive secondary metabolite of DB[a,l]P, the fjord region (-)-anti-11R,12S-dihydrodiol 13R,14S-epoxide [(-)-anti-DB[a,l]PDE] was used to investigate DNA damage via adduct formation and cell cycle arrest in human diploid fibroblast cell cultures (HDF). Synchronous HDF were exposed to increasing concentrations (0.014, 0.028 and 0.07 microM) of (-)-anti-DB[a,l]PDE and at 1, 12, 24 and 42 h after treatment cell pellets were analyzed for DNA adduct formation and cell cycle arrest. Exposure of HDF to 0.07 microM (-)-anti-DB[a,l]PDE caused a total DNA binding level of 113 pmol adducts/mg DNA (42 h after treatment). G(1) arrest was induced by this treatment, with 91% of the cells remaining in G(1) phase compared with the solvent-treated control cultures (50%) as analyzed by propidium iodide staining and flow cytometry. Further investigation of the percentage of cells in S phase by 5-bromo-2'-deoxyuridine incorporation confirmed the G(1) arrest in HDF treated with 0.07 microM (-)-anti-DB[a,l]PDE, with only 1.5% of the cells moving into S phase compared with 39% in the control 42 h after treatment. Induction of p53 and p21(WAF1) was demonstrated by western blot analysis.