Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property

Context: Therapeutic effects of α-l-guluronic acid with the greatest tolerability and efficacy (G2013) have been shown in experimental model of multiple sclerosis and other in vitro and in vivo examinations regarding α-l-guluronic acid; there are no toxicological researches on its safety although the pharmacological impacts have been recorded.

Objective: This study was designed to determine the acute and sub chronic toxicity of α-l-guluronic acid in healthy male and female BALB/c mice.

Materials and methods: For the acute toxicity study, the animals orally received five different single doses of α-l-guluronic acid and were kept under observation for 14?d. In the sub-chronic study, 24 male and female BALB/c mice were divided into four groups and treated daily with test substance preparation at dose levels of 0, 50, 250, and 1250?mg/kg body weight for at least 90 consecutive days. The mortality, body weight changes, clinical signs, hematological and biochemical parameters, gross findings, histopathological, and organs weight determinants were monitored during this study.

Results: The results of acute toxicity indicated that the LD50 of α-l-guluronic acid is 4.8?g/kg. We found no mortality or abnormality in clinical signs, body weight, relative organs weight, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.

Conclusions: Our results suggest that α-l-guluronic acid has high safety when administered orally in animals.     

Evaluation of an educational intervention in oral health for primary care physicians: a cluster randomized controlled study

Background

Family physicians are in frequent contact with patients, and their contribution to oral health promotion programs could be utilized more effectively. We implemented an oral health care (OHC) educational seminar for physicians and evaluated its impact on their knowledge retention in OHC.

Methods

We conducted an educational trial for primary care physicians (n?=?106) working in Public Health Centers in Tehran city. We launched a self-administered questionnaire about pediatric dentistry, general dental, and dentistry-related medical knowledge and backgrounds. Physicians in intervention group A (n?=?38) received an educational intervention (Booklet, Continuous Medical Education (CME), and Pamphlet), and those in group B (n?=?32) received only an OHC pamphlet. Group C (n?=?36) served as the control. A post-intervention survey followed four months later to measure the difference in the physicians’ knowledge; the Chi-square test, ANOVA and linear regression analysis served for statistical analysis.

Results

The intervention significantly increased the physicians’ oral health knowledge scores in all three domains and their total knowledge score (p?<? 0.001). Those physicians who had lower knowledge scores at the baseline showed a higher increase in their post-intervention knowledge. The models showed no associations between the background variables and the knowledge change.

Conclusion

The primary care physicians’ OHC knowledge improved considerably after an educational seminar with a reminder. These findings suggest that OHC topics should be included in physicians’ CME programs or in their curriculum to promote oral health, especially among non-privileged populations.

     

Vaccinia Virus GLV-1h153 Is Effective in Treating and Preventing Metastatic Triple-Negative Breast Cancer

OBJECTIVE:: This study aimed to investigate the therapeutic impact of a new oncolytic vaccinia virus in a triple-negative breast cancer (TNBC) murine model and its potential for treating distant metastatic disease. BACKGROUND:: TNBCs are aggressive tumors associated with a high metastatic rate. Their lack of targets for hormonal/biological therapy presents significant clinical challenges and a dire need for novel therapies. METHODS:: GLV-1h153, a replication-competent vaccinia virus, was tested against multiple cell lines. Cytotoxicity and viral replication were determined. Intratumoral (IT) or intravenous (IV) injection of GLV-1h153 (1 × 10 plaque-forming units) or phosphate buffered saline was tested in an orthotopic murine model, which reliably produces systemic metastasis. Tumors, lymph nodes, and metastatic organs (lung, liver, and brain) were harvested 5 and 8 weeks after treatment and prepared for histopathological review. Demonstration of metastasis was performed using immunofluorescence and hematoxylin and eosin (H&E) staining. RESULTS:: GLV-1h153 infected, replicated in, and killed all TNBC cell lines in vitro. In vivo, mean tumor volume 2 weeks after treatment was 22 (IT), 29 (IV) versus 245 mm (control; P < 0.002). Five weeks after treatment, all harvested lymph nodes and organs showed no evidence of metastatic cells. All harvested tumors showed complete response to treatment, with only necrosis and fibrosis on H&E staining 8 weeks after treatment. CONCLUSIONS:: This is the first study to demonstrate that TNBCs are killed by a novel vaccinia virus both in vitro and in vivo. Our results suggest that GLV-1h153 is a promising therapeutic agent for preventing and treating metastatic TNBC and warrants further clinical testing in patients.     

Merkel cell carcinoma on the right calf in association with chronic lymphocytic leukemia: A case report

This study showed a rare case of Merkel cell carcinoma (MCC) with atypical manifestations accompanied by chronic lymphocytic leukemia of B‐cell type that underwent chemotherapy and had poor prognosis. The findings suggest that the physicians should consider MCC when performing diagnosis and assess all possible associated risk factors like neoplasms to achieve good prognosis.     

Health-related quality of life in primary antibody deficiency

Patients with primary antibody deficiencies (PAD) are susceptible to recurrent and chronic infections and a variety of complications. This study was performed to assess quality of life (QoL) of PAD patients who were under long term treatment and regular follow-up.Thirty six adults with proved diagnosis of PAD, who had received regular intravenous immunoglobulin replacement therapy, were enrolled in this study. The QoL of selected PAD patients was measured by Medical Outcomes Study 36-item Short-Form (SF-36) Health Survey questionnaire.The patients with PAD showed significantly reduced scores in physical component in comparison with healthy age-sex matched control subjects (60.2±20.1 vs. 85.5±4.7, P<0.001). Mental component score was also significantly decreased in the patient's group (59.8±19.5 vs. 72.3±3.4, P=0.002). There was a reverse association between SF-36 scores and number of infections episodes (r=-0.73 P=0.003). The patients with long delay diagnosis showed significantly lower SF-36 scores (r=-0.62, P=0.003).The patients with PAD who were diagnosed timely and managed appropriately seem to have lower complications and better QoL. However, the patients with severe phenotypes and long delay in diagnosis showed lower QoL, even in medical management.