Exposure to heavy metals and the risk of osteopenia or osteoporosis: a systematic review and meta-analysis.

The relationship between heavy metal exposure and risk of osteopenia or osteoporosis has biological plausibility, yet it remains inconclusive; therefore, we conducted a systematic review and meta-analysis to evaluate the associations between exposure to heavy metals (i.e., cadmium, lead, and mercury) and the risk of osteopenia or osteoporosis. Databases of MEDLINE, Embase, Scopus, and Web of Science were searched through November 2019, to identify studies that evaluated the relationship between exposure to cadmium, lead, and mercury and risk of osteopenia or osteoporosis in adults. Fourteen eligible studies were included. Effect sizes expressed as pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated using weighted random-effect models. Exposure to cadmium (OR = 1.35; 95% CI: 1.17 to 1.56; P ≤ 0.001) and lead (OR = 1.15; 95% CI: 1.00 to 1.32; P = 0.05) was associated with an increased risk of osteopenia or osteoporosis, unlike mercury. Subgroup analyses showed cadmium exposure increased the risk of osteopenia or osteoporosis in older (> 65 yrs.; OR = 1.43; 95%CI: 1.08 to 1.88, P = 0.01) compared with younger (18-65 yrs.; OR = 1.24; 95% CI: 1.02 to 1.52, P = 0.03) adults. Also, lead exposure increased the risk in men (OR = 1.55; 95% CI: 1.15 to 2.09, P = 0.007) unlike in women. By contrast to urinary levels, blood (OR = 1.26; 95% CI: 1.08 to 1.47, P = 0.003) and dietary (OR = 1.46; 95% CI: 1.28 to 1.67, P < 0.001) levels of cadmium were associated with an increased risk of osteopenia or osteoporosis. Exposure to cadmium and lead may be associated with an increased risk of osteopenia or osteoporosis, although high heterogeneity was detected.

Proliferation inhibition of cisplatin-resistant ovarian cancer cells using drugs screened by integrating a metabolic model and transcriptomic data.

OBJECTIVES: If screening to find effective drugs is possible, the inhibition of proliferation using existing drugs can be a practical strategy to control the drug resistance of cancer. Development of a system-oriented strategy to find effective drugs was the main aim of this research. MATERIALS AND METHODS: An algorithm (transcriptional regulated flux balance analysis [TRFBA]) integrating a generic human metabolic model with transcriptomic data was used to identify genes affecting the growth of drug-resistant cancer cells. Drugs that inhibit activation of the target genes were found and their effect on the proliferation was experimentally evaluated. RESULTS: Experimental assessments demonstrated that TRFBA improves the prediction of cancer cell growth in comparison with previous algorithms. The algorithm was then used to propose the system-oriented strategy to search drugs effective in limiting the growth rate of the cisplatin-resistant A2780 epithelial ovarian cancer cell. Experimental evaluations resulted in the selection of azathioprine, terbinafine, hydralazine and sodium valproate that appropriately inhibit the proliferation of resistant cancer cells while minimally affecting normal cells. Furthermore, experimental data indicate that the selected drugs are synergistic and can be used in combination therapies. CONCLUSIONS: The proposed strategy was successful to identify drugs effective on the viability of resistant cancer cells. This strategy can enhance the potency of treatments for drug-resistant cancer cells and provides the possibility of using existing drugs.

Vitamin D status of type 2 diabetic patients compared with healthy subjects in the Islamic Republic of Iran.

An inverse relationship has been shown between vitamin D deficiency and type 2 diabetes mellitus (DM). In this cross-sectional study in Tehran, Islamic Republic of Iran, a country with a high prevalence of vitamin D deficiency, we determined the prevalence of vitamin D deficiency among 90 type 2 DM patients and 90 healthy subjects. Based on serum levels of 25-hydroxyvitamin D, the rates of deficiency (< 50 nmol/L) and insufficiency (50-75 nmol/L) were 59.0% and 27.0% respectively in patients with type 2 DM, and 47.0% and 24.0% respectively in healthy subjects. Using the national cut-offs for vitamin D deficiency, 64.0% women with DM and 47.4% of healthy women were suffering from different degrees of vitamin D deficiency. The prevalence of vitamin D deficiency in men with type 2 DM and healthy men were 42.7% and 22.2% respectively. None of the differences between the 2 groups was statistically significant.

Vitamin D status of type 2 diabetic patients compared with healthy subjects in the Islamic Republic of Iran

An inverse relationship has been shown between vitamin D deficiency and type 2 diabetes mellitus[DM]. In this cross-sectional study in Tehran, Islamic Republic of Iran, a country with a high prevalence of vitamin D deficiency, we determined the prevalence of vitamin D deficiency among 90 type 2 DM patients and 90 healthy subjects. Based on serum levels of 25-hydroxyvitamin D, the rates of deficiency[< 50 nmol/L] and insufficiency[50-75 nmol/L] were 59.0% and 27.0% respectively in patients with type 2 DM, and 47.0% and 24.0% respectively in healthy subjects. Using the national cut-offs for vitamin D deficiency, 64.0% women with DM and 47.4% of healthy women were suffering from different degrees of vitamin D deficiency. The prevalence of vitamin D deficiency in men with type 2 DM and healthy men were 42.7% and 22.2% respectively. None of the differences between the 2 groups was statistically significant

Hair regrowth with topical triiodothyronine ointment in patients with alopecia areata: a double-blind, randomized pilot clinical trial of efficacy.

BACKGROUND: Thyroid hormone receptors are expressed in hair follicles and it is known that thyroid hormones can have a positive effect on hair growth, i.e. process which is disrupted in alopecia areata. OBJECTIVES: The aim of this study was to determine the efficacy of topical triiodothyronine in patients with patchy alopecia areata. METHODS: Ten patients with patchy alopecia areata were treated with triiodothyronine and placebo applied twice daily to either of two bilaterally symmetrical patches for 12 weeks. The two sides were randomly assigned following simple randomization procedure to one of the two treatment groups. The patients and the investigator were blinded to the content of the tubes. Hair regrowth was evaluated every 4 weeks. Blood samples for measurements of complete blood count along with thyroid function (T3, T4 and TSH) and liver function tests were taken at the baseline and at the end of study. RESULTS: After 12 weeks of treatment, there was no statistically significant difference between the outcome in terms of reduction of the patch size and hair regrowth. No adverse effects were noted. CONCLUSION: Triiodothyronine in the studied dosage and formulation was safe but not more effective than placebo. However, newer thyroid hormone analogues might be more effective and evaluating their effects probably warrants further consideration.

Population-based severity, onset and type of drug-drug interactions in prescriptions.

Inappropriate drug combinations occur frequently and may lead to serious adverse events. In Iran, drug overdose and interactions are relatively common but rarely reported and are mainly derived from admitted subjects. The aim of this study was to determine the prevalence of possible drug-drug interactions via a population database survey in Mashhad, Iran. In this survey all prescriptions paid by insurance companies in the period 21rst March 2006 to 20th March 2008 were studied retrospectively. Data were gathered from the Division of Rational Use Drug, Food and Drug Vice Chancellor of Mashhad University of Medical Sciences, Iran. Drug interactions were categorized based on severity, onset and dynamic/kinetic nature. Incidence was calculated based on the number of interactions/1000 prescriptions. In total 11,562,808 prescriptions were studied, among which 5% showed interactions. Two hundred and four types of potential interactions were detected. Belladonna, phenytoin sodium, cimetidine, propranolol hydrochloride, gentamicin, acetylsalicylic acid (ASA), Antacid, theophylline and carbamazepine were the most common medications. Among them, 54% showed dynamic and 34% kinetic interactions, 11% were categorized to be both and 76% displayed rapid-onset interactions. Moderate interactions were the most dominant (70%) phenomenon. Dynamic and kinetic interactions significantly differed with respect to the onset of interactions (P < 0.001). A rather different pattern of drug-drug interaction exists in Iran, highlighting the need for a nationwide program on related education and a stronger focus on severe and rapid-onset interactions. Further studies warrant the need to explore high-risk patients.

Increased levels of IL-10, IL-12, and IFN- in patients with visceral leishmaniasis.

Visceral leishmaniasis remains a serious public health problem in developing countries. Cytokines have a crucial role in the pathogenesis of this disease. We evaluated plasma levels of IL-10, IL-12 and IFN- in 32 patients with active visceral lieshmaniasis, in 29 siblings of the patients and in 23 normal individuals in an endemic area to look for correlations between the clinical outcome of infection and the plasma cytokine levels. An analysis was made with a skin test and a quantitative sandwich enzyme immunoassay. Data were analyzed with the Mann Whitney test and the Kruskal Wallis test. The cytokine levels were significantly higher in the patients than in the control groups. We concluded that normalization of the plasma level of IFN- can serve as a reliable parameter for considering the patient as cured.

Increased levels of IL-10, IL-12, and IFN- in patients with visceral leishmaniasis

Visceral leishmaniasis remains a serious public health problem in developing countries. Cytokines have a crucial role in the pathogenesis of this disease. We evaluated plasma levels of IL-10, IL-12 and IFN- in 32 patients with active visceral lieshmaniasis, in 29 siblings of the patients and in 23 normal individuals in an endemic area to look for correlations between the clinical outcome of infection and the plasma cytokine levels. An analysis was made with a skin test and a quantitative sandwich enzyme immunoassay. Data were analyzed with the Mann Whitney test and the Kruskal Wallis test. The cytokine levels were significantly higher in the patients than in the control groups. We concluded that normalization of the plasma level of IFN- can serve as a reliable parameter for considering the patient as cured.

Ethical and legal aspects of organ transplantation in Iran.

The great advances in the technology of organ preservation, immunosuppression, and surgical procedures have resulted in success in saving lives. However, these advantages have raised major ethical, policy, and religious problems in organ transplantation. Extensive efforts have been made to address these problems in different communities. In this study the transplantation program and implementation of legislation in Iran is reviewed. The history of the organ transplantation "Act of Organ Transplantation and Brain Death," which allows controlled living unrelated donors access to renal transplantation, is discussed as the main subject.