Standardised mortality ratios in people exposed to sulphur mustard during the Iran-Iraq war: a retrospective study with 39-year follow-up.

OBJECTIVES: Sulphur mustard (SM) is a chemical weapon agent that was extensively used by Iraqi troops during the Iran-Iraq war (1980-1988), resulting in exposure among Iranian military personnel and civilians. However, there is limited and conflicting information about the long-term mortality effects of SM exposure. This study aimed to determine the standardised mortality ratios (SMRs) in individuals exposed to SM gas during the Iran-Iraq war. STUDY DESIGN: This was a retrospective follow-up study. METHODS: Data were obtained from the Veterans and Martyr Affair Foundation of Iran (VMAF) regarding all confirmed individuals who were exposed to SM during the Iran-Iraq war (1980-1988) up to 30 March 2019. The mortality rate, cumulative mortality and SMR with 95 % confidence intervals (CIs) were calculated to assess mortality in chemical warfare survivors (CWS), and results were compared with the general Iranian population. Overall survival was analysed using the Kaplan-Meier curve, and the log-rank test was employed to compare survival probability across different categories. RESULTS: Among the 48,067 confirmed CWS, a total of 4358 (9.1 %) individuals had died by the end of the study period (30 March 2019), with a mean age of 55.5 ± 14.4 years at the time of death. Overall, at the 39-year follow-up, the mortality rate due to all causes of death for people who were exposed to SM was lower than the general Iranian population (SMR: 0.70, 95 % CI: 0.68-0.72). However, cause-specific SMR analysis showed that the mortality rate due to liver cancer (SMR: 1.98, 95 % CI: 1.59-2.45), poisonings (SMR: 1.92, 95 % CI: 1.52-2.38), respiratory disorders (SMR: 1.59, 95 % CI: 1.46-1.73) and multiple myeloma (SMR: 1.72, 95 % CI: 1.06-2.62) were approximately twofold higher in CWS than the general population. CONCLUSIONS: This study provides valuable insights into the mortality effects of SM exposure among the Iranian population affected by the Iran-Iraq war. The results emphasise the importance of continued monitoring and support for individuals exposed to SM, particularly in the context of managing and addressing the heightened risks associated with liver cancer, poisonings, respiratory disorders and multiple myeloma. Further research and interventions may be necessary to mitigate these specific health challenges in the affected population.

Molecular mechanisms involved in the protective actions of Selective Estrogen Receptor Modulators in brain cells.

Synthetic selective modulators of the estrogen receptors (SERMs) have shown to protect neurons and glial cells against toxic insults. Among the most relevant beneficial effects attributed to these compounds are the regulation of inflammation, attenuation of astrogliosis and microglial activation, prevention of excitotoxicity and as a consequence the reduction of neuronal cell death. Under pathological conditions, the mechanism of action of the SERMs involves the activation of estrogen receptors (ERs) and G protein-coupled receptor for estrogens (GRP30). These receptors trigger neuroprotective responses such as increasing the expression of antioxidants and the activation of kinase-mediated survival signaling pathways. Despite the advances in the knowledge of the pathways activated by the SERMs, their mechanism of action is still not entirely clear, and there are several controversies. In this review, we focused on the molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a response to treatment with raloxifene and tamoxifen.

Ceramides and diabetes mellitus: an update on the potential molecular relationships.

Recent evidence suggests that ceramides can play an important pathophysiological role in the development of diabetes. Ceramides are primarily recognized as lipid bilayer building blocks, but recent work has shown that these endogenous molecules are important intracellular signalling mediators and may exert some diabetogenic effects via molecular pathways involved in insulin resistance, ß-cell apoptosis and inflammation. In the present review, we consider the available evidence on the possible roles of ceramides in diabetes mellitus and introduce eight different molecular mechanisms mediating the diabetogenic action of ceramides, categorized into those predominantly related to insulin resistance vs those mainly implicated in ß-cell dysfunction. Specifically, the mechanistic evidence involves ß-cell apoptosis, pancreatic inflammation, mitochondrial stress, endoplasmic reticulum stress, adipokine release, insulin receptor substrate 1 phosphorylation, oxidative stress and insulin synthesis. Collectively, the evidence suggests that therapeutic agents aimed at reducing ceramide synthesis and lowering circulating levels may be beneficial in the prevention and/or treatment of diabetes and its related complications.

A systematic review and meta-analysis on the epidemiology of antibiotic resistance of Vibrio cholerae in Iran.

BACKGROUND: Cholera, an acute diarrheal disease caused by Vibrio cholerae (V. cholerae), is an endemic disease and a major public health problem in Iran. Antibiotic therapy can decrease duration of the disease, transmission of infection and contamination of the environment. Considering different pattern of V. cholerae antibiotic resistance around the world, the aim of the current systematic review and meta-analysis was to evaluate the prevalence of antibiotic resistance of V. cholerae in Iran. METHODS: A systematic review of the literature was performed using related keywords in the electronic national and international databases including SID, Irandoc, Iran Medex and Magiran as well as PubMed, Scopus, Google Scholar and ISI web of knowledge. Up to July 31, 2018, 27 eligible papers were included in our meta-analysis based on the defined inclusion criteria. RESULTS: V. cholerae O1 was the most prevalent strain isolated in Iran and exhibited a high resistance rate against numerous antibiotics including chloramphenicol (33.6%), oxytetracycline (40.2%), trimethoprim/sulphamethoxazole (86%), tetracycline (34.5%), furazolidone (69.8%), streptomycin (93.8%), polymyxin (80.7%), ampicillin (32.1%), nalidixic acid (88.9%), kanamycin (29%) and amoxicillin (30.5%). CONCLUSIONS: According to the meta-analysis results, antibiotic therapy with ciprofloxacin, doxycycline, erythromycin, gentamicin, azithromycin, cefixime and cefepime could be effective for the treatment of severe cases of cholera in Iran.

Uric acid and bone mineral density in postmenopausal osteoporotic women: the link lies within the fat.

The association between serum uric acid (SUA) levels and bone mineral density (BMD) is controversial. Fat accumulation is linked to SUA and BMD, thus possibly explaining the mixed results. We found that adiposity drives part of the association between SUA and BMD in women with postmenopausal osteoporosis. INTRODUCTION: Both positive and negative associations between SUA and BMD have been reported. SUA levels and BMD increase with higher body weight and other indices of adiposity; hence, the association between SUA and BMD might be a consequence of the confounding effect of adiposity. We investigated in this cross-sectional study whether the association between SUA and BMD is independent of measures of fat accumulation and other potential confounders. METHODS: SUA levels, femur BMD, markers of bone metabolism, body mass index (BMI), fat mass (FM), waist circumference (WC), and abdominal visceral fat area were measured in 180 treatment-naive postmenopausal osteoporotic women (mean age 66.3 ± 8.5 years, age range 48-81 years). RESULTS: Women with higher SUA levels (third tertile) had significantly higher femur BMD and lower cross-linked C-terminal telopeptide of type I collagen (CTX) and bone alkaline phosphatase (bALP) levels. SUA levels were positively associated with all indices of adiposity. In multivariable analysis with femur BMD as dependent variable, the association between logarithmic (LG)-transformed SUA levels and BMD (beta = 0.42, p < 0.001) was lessened progressively by the different indices of adiposity, like LG-BMI (beta = 0.22, p = 0.007), LG-WC (beta = 0.21, p = 0.01), LG-FM (beta = 0.18, p = 0.01), and LG-abdominal visceral fat area (beta = 0.12, p = 0.05). The association between SUA levels and markers of bone metabolism was dependent on the effect of confounders. CONCLUSION: In postmenopausal osteoporotic women, the strong univariable association between SUA levels and femur BMD is partly explained by the confounding effect of indices of adiposity.

Preventing cardiovascular heart disease: Promising nutraceutical and non-nutraceutical treatments for cholesterol management.

Hypercholesterolemia is one of the major risk factors for the development of cardiovascular disease. Atherosclerosis resulting from hypercholesterolemia causes many serious cardiovascular diseases. Statins are generally accepted as a treatment of choice for lowering low-density lipoprotein (LDL) cholesterol, which reduces coronary heart disease morbidity and mortality. Since statin use can be associated with muscle problems and other adverse symptoms, non-adherence and discontinuation of statin therapy often leads to inadequate control of plasma cholesterol levels and increased cardiovascular risk. Moreover, there is compelling evidence on the presence of still considerable residual cardiovascular risk in statin-treated patients. Ezetimibe improves cholesterol-lowering efficacy and provides mild additional cardiovascular protection when combined with statin treatment. Despite a favorable safety profile compared to statins, ezetimibe-induced cholesterol-lowering is modest when used alone. Hence, there is a critical need to identity additional effective hypolipidemic agents that can be used either in combination with statins, or alone, if statins are not tolerated. Thus, hypolipidemic agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, apolipoprotein B-100 antisense oligonucleotides, cholesteryl ester transfer protein (CETP) inhibitors, and microsomal triglyceride transfer protein (MTTP) inhibitors, as well as yeast polysaccharides (beta-glucans and mannans) and compounds derived from natural sources (nutraceuticals) such as glucomannans, plant sterols, berberine, and red yeast rice are being used. In this review, we will discuss hypercholesterolemia, its impact on the development of cardiovascular disease (CVD), and the use of yeast polysaccharides, various nutraceuticals, and several therapeutic agents not derived from 'natural' sources, to treat hypercholesterolemia.

SERUM LEVELS OF FIBROBLAST GROWTH FACTOR 21 IN TYPE 2 DIABETIC PATIENTS.

BACKGROUND AND PURPOSE: Fibroblast growth factor 21 (FGF21) has recently been identified as a metabolic regulator, but its physiological role is still not completely known. The aim of this study was to evaluate serum FGF21 levels in an Iranian population with type 2 diabetes. MATERIALS AND METHODS: This cross-sectional study was conducted in patients with type 2 diabetes. All patients were evaluated for fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, urea and creatinine. Participants were divided into two groups with poorly-controlled and well-controlled diabetes based on their HbA1c levels. Healthy non-diabetic subjects (matched with patients in terms of age, sex and body mass index [BMI]) were also recruited as control group. Serum FGF21 concentrations were determined in all subjects using ELISA. RESULTS: Of the evaluated 141 subjects, 49 (34.8%) were categorized as having well-controlled diabetes, 66 (46.8%) had poorly-controlled diabetes, and there were 26 subjects in the normal control group. Mean serum FGF-21 concentration was 337.89±283.67 ng/L in the diabetic group and 237.25±43.22 ng/mL in the non-diabetic group (p<0.001). Mean serum FGF21 level was 237.25 ± 43.22 ng/mL in the control group, 309.81 ± 301.68 ng/mL in the well-controlled diabetic group, and 358.73 ± 269.98 ng/mL in the poorly controlled diabetic group. Serum FGF21 level in the poorly controlled diabetic group was significantly higher than that in the well-controlled diabetic and the healthy control groups (p=0.02) but there was no significant difference between the well-controlled and healthy groups. There was no significant association between serum FGF21 levels with lipid levels, presence of diabetic complications and BMI (p > 0.05). CONCLUSIONS: The present results suggested an association between elevated serum levels of FGF21 and poor control of diabetes. Future studies are warranted to elucidate the prognostic role of these elevated levels of FGF21 in diabetic subjects.

Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: a systematic review and meta-analysis of clinical trials.

AIMS: To evaluate the magnitude of the effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) levels through a systematic review and meta-analysis of clinical trials. METHODS: A random-effects model (using DerSimonian-Laird method) and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using the I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using an unrestricted maximum likelihood method to evaluate the association between statin-induced elevation of plasma PCSK9 concentrations with duration of treatment and magnitude of LDL cholesterol reduction. RESULTS: A total of 15 clinical trials examining the effects of statin therapy on plasma PCSK9 levels were included. Meta-analysis of data from single-arm statin treatment arms [weighted mean difference (WMD) 40.72 ng/ml, 95% confidence interval (CI) 34.79, 46.65; p < 0.001] and randomized placebo-controlled trials (WMD 22.98 ng/ml, 95% CI 17.95, 28.01; p < 0.001) showed a significant increase in plasma PCSK9 concentrations after statin therapy, irrespective of the type of statin administered in either of the analyses (single-arm or randomized placebo-controlled trial). There was no significant elevation of plasma PCSK9 levels with statin/ezetimibe combination therapy compared with statin monotherapy (WMD 23.14 ng/ml, 95% CI -1.97, 48.25; p = 0.071); however, removal of one study in the meta-analysis yielded a significant result in the sensitivity analysis (WMD 31.41 ng/ml, 95% CI 7.86, 54.97; p = 0.009). CONCLUSIONS: This meta-analysis suggests that statin therapy causes a significant increase in plasma PCSK9 concentrations.

Ameliorative effects of Nigella sativa on dyslipidemia.

INTRODUCTION: Dyslipidemia is an established risk factor for ischemic heart disease. Nigella sativa (NS) is a medicinal plant that has been used for the treatment and prevention of a variety of diseases, in particular hyperlipidemia. METHODS: We reviewed the existing literature published until 2014 by using the following keywords: ''Nigella sativa'', ''black cumin'', ''black seeds'', ''thymoquinone'', and ''lipid''. RESULTS: In the conducted studies, different preparations of NS including seed powder (100 mg-20 g daily), seed oil (20-800 mg daily), thymoquinone (3.5-20 mg daily), and seed extract (methanolic extract especially), were shown to reduce plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, but the effect on high-density lipoprotein cholesterol (HDL-C) was not significant. NS and thymoquinone have been reported to be safe and well tolerated with no severe adverse effect. In clinical trials, NS was found to be effective when added as adjunct to standard antihyperlipidemic and antidiabetic medications. Lipid-modifying effects of NS could be attributed to the inhibition of intestinal cholesterol absorption, decreased hepatic cholesterol synthesis, and up-regulation of LDL receptors. CONCLUSIONS: Overall, the evidence from experimental and a clinical studies suggests that NS seeds are a promising natural therapy for dyslipidemic patients.

Comparative trial of Aloe vera/olive oil combination cream versus phenytoin cream in the treatment of chronic wounds.

OBJECTIVE: Aloe vera is a medicinal plant that has been traditionally used to accelerate wound healing. Olive oil is also a natural product that may contribute to wound healing owing to its antimicrobial and anti-inflammatory effects. The present study aimed to evaluate the effect of an Aloe vera-olive oil (AVO) combination cream on the healing process of chronic wounds. METHOD: In this randomised, double-blind, comparator-controlled, parallel-group trial, patients with chronic wounds were treated with either AVO cream or phenytoin cream as the standard treatment for a period of 30 days. Wound healing was evaluated using Bates-Jensen assessment tool and the severity of pain was assessed using a visual analogue scale (VAS). RESULTS: After initial assessment, 60 patients with chronic wounds (41 with pressure ulcer, 13 with diabetic wounds and 6 with venous ulcers), were recruited and randomised into 2 groups of 30. After 30 days of treatment, significant improvements in the wound size, depth, and edges; necrotic tissue type and amount; exudate type and amount; colour of wound surroundings; and peripheral tissue oedema score were observed in the AVO cream group (p<0.001). The total score of wound healing showed significant improvement with both AVO (p<0.001) and phenytoin (p<0.01) creams, although AVO was more efficacious (p<0.001). Likewise, although both treatments reduced the initial VAS score, the efficacy of AVO was significantly greater (p<0.001). CONCLUSION: AVO cream significantly accelerates biological healing of chronic wounds and helps to reduce pain severity with a higher efficacy compared with phenytoin cream.

A randomized, double-blind, placebo-controlled trial on the efficacy and tolerability of sertraline in Iranian veterans with post-traumatic stress disorder.

BACKGROUND: Unlike civilian post-traumatic stress disorder (PTSD), the efficacy of sertraline for the treatment of combat-related PTSD has not yet been proven. The present study aimed to evaluate the clinical efficacy of sertraline against combat-related PTSD in a randomized, double-blind, placebo-controlled trial. METHOD: Seventy Iranian veterans of the Iran-Iraq war who met the DSM-IV criteria for diagnosis of PTSD were randomized to receive either flexibly dosed sertraline (50-200 mg/day) (n=35, completers=32) or placebo (n=35, completers=30) for 10 weeks. Efficacy was evaluated by the Impact of Event Scale--Revised (IES-R) and the Clinical Global Impression scale--Severity (CGI-S) and Improvement (CGI-I) ratings. Responder criteria were defined as a ≥30% reduction in the IES-R total score plus a CGI-I rating of 'much' or 'very much' improved. RESULTS: On both intention-to-treat (ITT) and per protocol (completer) methods of analysis, the mean reductions in the IES-R total and subscale (re-experiencing/intrusion, avoidance/numbing and hyperarousal) scores (p<0.001) and also in the CGI-S score (p<0.01) were significantly greater in the sertraline group than in the placebo group. For the CGI-I, the mean endpoint score was significantly lower in the sertraline group than in the placebo group (p≤0.001). The number of responders in the sertraline group was significantly higher than in the placebo group (44% v. 3%, p≤0.001). Sertraline was well tolerated, with a 6% discontinuation rate as a result of adverse reactions. CONCLUSIONS: The results of this study suggest that sertraline can be an effective, safe and tolerable treatment for combat-related PTSD in Iranian veterans.

Antibacterial efficacy of lytic bacteriophages against antibiotic-resistant Klebsiella species.

Bacterial resistance to antibiotics is a leading and highly prevalent problem in the treatment of infectious diseases. Bacteriophages (phages) appear to be effective and safe alternatives for the treatment of resistant infections because of their specificity for bacterial species and lack of infectivity in eukaryotic cells. The present study aimed to isolate bacteriophages against Klebsiella spp. and evaluate their efficacy against antibiotic-resistant species. Seventy-two antibiotic-resistant Klebsiella spp. were isolated from samples of patients who referred to the Ghaem Hospital (Mashhad, Iran). Lytic bacteriophages against Klebsiella spp. were isolated from wastewater of the septic tank of the same hospital. Bactericidal activity of phages against resistant Klebsiella spp. was tested in both liquid (tube method; after 1 and 24 h of incubation) and solid (double-layer agar plate method; after 24 h of incubation) phases. In each method, three different concentrations of bacteriophages (low: <10(4) PFU/mL, medium: 10(4)-10(7) PFU/mL, and high: >10(7) PFU/mL) were used. Bacteriophages showed promising bactericidal activity at all assessed concentrations, regardless of the test method and duration of incubation. Overall, bactericidal effects were augmented at higher concentrations. In the tube method, higher activity was observed after 24 h of incubation compared to the 1-h incubation. The bactericidal effects were also higher in the tube method compared to the double-layer agar plate method after 24 h of incubation. The findings of the present study suggest that bacteriophages possess effective bactericidal activity against resistant Klebsiella spp. These bactericidal activities are influenced by phage concentration, duration of incubation, and test method.

Selenium supplementation and premature (pre-labour) rupture of membranes: a randomised double-blind placebo-controlled trial.

The aim was to determine if selenium supplementation during pregnancy reduces the occurrence of premature (pre-labour) rupture of membranes (PROM). A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomised to receive 100 microg of selenium (n = 83, drop-outs = 22) or a placebo (n = 83, drop-outs = 19) per day until delivery. The incidence of PROM, as well as serum selenium concentrations were evaluated at baseline and at the end of the study. Supplementation with selenium was associated with a significant increase in mean serum selenium concentration at term (p < 0.001). In contrast, mean serum selenium concentration remained unchanged in the control group (p > 0.05). The incidence of PROM was significantly lower in the selenium group (n = 8, 13.1%) than in the control group (n = 22, 34.4%) (p < 0.01). Our findings indicate that selenium supplementation (100 microg/day) in pregnant women effectively reduces the incidence of PROM.

Antibiotic resistance profiles of Salmonella serotypes isolated from animals in Iran: a meta-analysis.

BACKGROUND: Salmonella infection (salmonellosis) is a zoonotic bacterial disease. Widespread use of antibiotics in livestock and poultry production for different purposes such as treatment and growth promotion has led to the emergence of antibiotic-resistant Salmonella, causing treatment of Salmonella infections more difficult with each passing year. AIMS: To determine the antibiotic resistance prevalence of Salmonella serotypes isolated from animals in different provinces of Iran. METHODS: To find eligible articles, we searched the international and national electronic databases using appropriate keywords in English and Persian. RESULTS: After applying predefined criteria, 54 articles reporting antibiotic resistance profiles of Salmonella serotypes were included. Salmonella isolates were mostly resistant against nalidixic acid (67%), tetracycline (66.9%), and streptomycin (49.6%), followed by trimethoprim/sulfamethoxazole (41.6%) and kanamycin (23.6%). The highest sensitivity was observed against imipenem, meropenem, and cefepime with 1.7%, 1.4%, and 1.9% of all isolates being resistant, respectively. CONCLUSION: Results revealed that the prevalence of resistant isolates to nalidixic acid, tetracycline and streptomycin is high and their use must be restricted. In addition, resistance to other antibiotics such as chloramphenicol, ampicillin, cephalothin, cefixime, and enrofloxacin is at an alarming level that calls for attention in the future infection control and antibiotic stewardship programs.

Prevalence of obesity and its association with socioeconomic factors in elderly Iranians from Razavi-Khorasan province.

There are few data regarding the prevalence of obesity and its socioeconomic determinants among elderly individuals, particularly in Iran. We wished to determine the prevalence of overweight and obesity in free-living elderly people and the relationship to nutritional and socioeconomic factors in the Razavi-Khorasan province of Iran. Free-living elderly persons (917 males/1045 females), aged > or =60 years, were recruited using cluster sampling. Overweight and obesity were evaluated using body mass index (BMI) and subjects were categorized as thin (BMI <18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (> or =30 kg/m2). The association between the prevalence of overweight or obesity with socioeconomic and demographic factors, including gender, place of residence, literacy, type of living, source of income, use of supplements during the past 3 months, and employment status, was examined using regression analysis. The distribution of BMI values indicated that 13, 46.5, 28.9, and 11.7% of the total population were thin, normal, overweight, and obese, respectively. The prevalence of central obesity was higher among Iranian women than men (63.1 vs. 18.6%, respectively). Regression analysis results indicated that gender (p < 0.001), place of residence (p < 0.001), literacy (p = 0.01), and source of income (p < 0.001) were significantly associated with the incidence of overweight or obesity. This study showed that 40.6% of elderly subjects were overweight or obese. Results reinforce the need to plan strategies for primary prevention of this fast-growing public health problem.

ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials.

INTRODUCTION: Tolerability problems in treating hypercholesterolemic patients undergoing statin treatment are of growing concern to physicians and patients, thus underlining the need for an agent with a similar mechanism but minimal side effects. A drug with a somewhat similar mechanism to statins but free of muscular side effects is ETC-1002 (bempedoic acid). It inhibits cholesterol biosynthesis at a step preceding HMG-CoA reductase, i.e. ATP citrate lyase (ACLY). A prodrug, ETC-1002 is converted to the active agent only in liver, not in skeletal muscle, and this may prevent any myotoxic activity. Area covered: The mechanism of ETC-1002 activity is described in detail, considering that ACLY inhibition markedly attenuated atherosclerosis in animal models. Clinical studies are also reported. Expert opinion: Present day LDL-C lowering treatments lead to significant reductions of cardiovascular (CV) events but, at times, the need to interrupt statin treatment appears to be dangerous due to a rapid rise in CV risk. The excellent tolerability of ETC-1002 makes it a useful alternative, either alone or as an adjunct to ezetimibe, for patients with statin intolerance needing to achieve significant CV risk reduction. ETC-1002 is also associated with a marked fall in high-sensitivity C-reactive protein.

Appropriateness of statin prescription in the elderly.

Statins, the most widely used drugs in the Western world, have become a pivotal component in the primary and secondary prevention of vascular diseases. Although benefits have been well documented in younger-than-75-year-old individuals, the value of statins in people aged >75years and over is controversial. The CTT meta-analysis calculated an absolute risk reduction of 0.6%/year per 38.7mg/dl reduction in LDL-C levels in patients aged >75years, that would translate into a number needed to treat of 167. However, the absolute effect of a 38.7mg/dl cholesterol lowering on the rate of annual ischemic heart disease mortality is 10-fold larger in older vs younger patients. In order to advise physician prescription, three major Guidelines have been published over the last few years, i.e. the AHA/ACC and the NLA in the US, and the ESC/EAS in Europe. Moreover, statin prescription in the elderly should also consider the cardiovascular outcomes of elderly patients reported in classical statin preventive trials which give important clues on adherence and persistence of use, as well as on drug safety. The present review discusses benefits of intensive vs moderate statin therapy, justifications for the use of aggressive lipid management in the very old and the use of statins in frail elderlies. The final decision on the therapeutic strategy with statins in elderlies at higher risk to develop cardiovascular events should be always based on a careful analysis of the patient's general health and on the presence of metabolic abnormalities or drug interactions potentially leading to risk.

Stable and sustained release liposomal formulations of celecoxib: In vitro and in vivo anti-tumor evaluation.

Celecoxib (CLX) is a selective COX-2 inhibitor with anticancer potential in a COX-2 dependent and independent manner. CLX's low water solubility has a dose limiting effect on its utilization in cancer treatment. Here, we developed liposomal drug delivery systems to allow a systemic administration and increase tumor accumulation of CLX based on the enhanced permeability and retention (EPR) mechanism. Nine liposomal formulations has been prepared with different phospholipid compositions; among them three sets of liposomal formulations were selected based on characterization and stability for further studies. Anti-tumor effects of CLX-entrapped liposomal formulations were tested in vitro by cytotoxicity test and in vivo in BALB/c mice bearing C26 colon carcinoma. Biodistribution of liposomal-CLX has been studied by radiolabeling of CLX with I125.The selected formulations had average size of about 100 nm, a narrow monomodal distribution with storage stability of at least one year at 4 °C. The HSPC/DSPG/cholesterol/DSPE-PEG2000/CLX (65/10/10/5/10 M ratio) liposomal formulation had slowest release profile and greatest antitumor effects in vivo. This liposomal I125CLX formulation had a three times more accumulation in tumor site in comparison to the free I125CLX. Liposomal CLX may serve as a safe, slow release and effective anti-tumor agent and merits further investigation.

Paraoxonase-1 activity in patients with cancer: A systematic review and meta-analysis.

PURPOSE: Paraoxonase-1 (PON1) is a lipolactonase implicated in the elimination of carcinogenic free radicals and in the scavenging mechanisms to maintain oxidative balance. The objective of the present systematic review and meta-analysis was to evaluate possible alterations in serum PON1 activity in patients with cancer. METHODS: A systematic search of the observational studies in humans published in the last 15 years was performed through Medline databases following the PRISMA and STARLITE statements. Further, a keyword-based computerized search with restrictions on publication date, and a meta-analysis of case-control studies was performed. RESULTS: In total, 23 studies were included most of which reported decreased PON1 activity in patients with cancer. This could indicate impaired defense ability against oxidative stress with potential implications in cell proliferation, promotion of genetic instability, and alterations in cellular sensitivity to chemotherapy. CONCLUSION: This systematic review and meta-analysis confirms a consistent association between cancer and decreased serum PON1 activities. These findings may open fruitful lines of research with clinical relevance, and an understanding of molecular alterations underlying carcinogenesis.

The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: a systematic review of clinical trials.

Despite benefits of systemic chemotherapy in breast cancer treatment, several patients with early-stage breast cancer will develop metastatic breast cancer (MBC). Doxorubicin is among the most active agents against MBC. However, the use of doxorubicin is related to some life-threatening side effects including cardiotoxicity. Many efforts were made to lessen the side effects of doxorubicin and improve its efficacy. Pegylated liposomal doxorubicin (PLD) is a product claimed to achieve these two objectives because of its different pharmacokinetic profile. The aim of this study was to determine the side-effect profile of PLD in MBC through a systematic review of phase II clinical trials. A literature search in PubMed-MEDLINE was performed using terms covering nano-based pharmaceutical systems, 'breast cancer' and 'doxorubicin'. Articles were evaluated according to the inclusion criteria. Reported hematological and non-hematological side effects were categorized. Out of 718 articles that were initially identified, 8 were in accordance with the inclusion criteria. We found that the most important side effects of PLD were skin toxicity and mucositis, but the proportion of patients who showed grade III and IV of these side effects was relatively low. On the other hand, the occurrence of cardiotoxicity, the most important problem with doxorubicin, was considerably reduced in patients treated with PLD. Although PLD has demonstrated a lower toxicity profile than conventional anthracyclines, it has also new side effects. However, it seems that the reduced cardiotoxicity of PLD has made it a more appropriate option in patients with MBC, especially in those with risk factors for cardiac diseases.