Study of waterpipe smoking topography in Fars province of Iran.

Despite a sharp increase in the use of the waterpipe (WP) has been noted recently in Iran, no information is available for the smoking behavior and topography parameters. The present study is intended to obtain the inhalation and smoking topography parameters for the Iranian WP smokers. The smoking data collected from 122 smoking sessions, including 192 WP smokers in the Iranian Fars province have been used to perform smoking topography assessments. The influence of demographic and smoking parameters on puffing data is obtained. Results have indicated that gender and tobacco type strongly affect puff volume and duration. Women smokers inhale smaller volume of smoke than men and puff duration is significantly increased for regular smokers than occasional smokers. However, the results of the present study have not revealed a major effect of age, residence and setting on the puffing behavior.

Melatonin attenuates chemical-induced cardiotoxicity.

Environmental chemicals and drugs can induce cardiotoxicity, mainly by generating free radicals. Reactive oxygen species play a critical role in the pathogenesis of cardiac tissue injury. This highlights a need for prevention of cardiotoxicity by scavenging free radicals. Melatonin has been shown to act as a protector against various conditions in which free radicals cause molecular and tissue injury. Some of the mechanisms by which melatonin operates as a free radical scavenger and antioxidant have been identified. The importance of endogenous melatonin in cardiovascular health and the benefits of melatonin supplementation in different cardiac pathophysiological disorders have been shown in a variety of model systems. Melatonin continues to attract attention for its potential therapeutic value for cardiovascular toxicity. The therapeutic potential of melatonin in treatment of cardiotoxicities caused by various chemicals along with suggested molecular mechanisms of action for melatonin is reviewed.

A review on the cardioprotective mechanisms of metformin against doxorubicin.

Doxorubicin (DOX) is an antineoplastic agent obtained from Streptomyces peucetius. It is utilized in treating different kinds of cancers, such as leukemia, lymphoma, and lung, and breast cancers. The main side effect of DOX is cardiotoxicity. Metformin (MET) is an antihyperglycemic drug used for type 2 diabetes treatment. It is proposed that MET has a protective effect against DOX cardiotoxicity. Our review demonstrated that MET has several possible mechanisms of action, which can prevent or at least reduce DOX cardiotoxicity including a decrease of free radical generation and oxidative stress, 5' adenosine monophosphate-activated protein kinase activation, and ferritin heavy chain expression in cardiomyocytes cells. The combination of MET and DOX has been shown to enhance the anticancer activity of DOX by a number of authors. The literature reviewed in the present report supports the hypothesis that MET can reduce the cardiotoxicity that often occurs with DOX treatment.

Comparative Assessment of the Whole-cell Pertussis Vaccine Potency Using Serological and Intracerebral Mouse Protection Methods.

One of the most important QC tests of whole-cell pertussis vaccine (WCPV) is potency test. In this regard, mouse protection test (MPT) is the current potency method, which is associated with severe animal distress and large variability in results. The purpose of this study was to assess Pertussis Serological Potency Test (PSPT) as a serological alternative method to intracerebral challenge in MPT assay. In the current study, the potency of three experimental batches of WCPV (1, 2, and 3) and standard vaccine were compared using MPT and PSPT methods. In the MPT method, mice were immunized with tests and standard vaccines. After 2 weeks, they were intracerebrally challenged with Bordetella pertussis strain (18323). The potency was calculated via parallel line analysis based on the numbers of survivors 2 weeks after the challenge. Similar to MPT method, mice were immunized in the PSPT method and bled after 4 weeks. In the next step, sera were titrated by 18323-WCP-ELISA assay and potency values were estimated via parallel line analysis. Pearson correlation test was used to measure the strength of association between MPT and PSPT assay results. The potency values of the experimental laboratory batches 1, 2, and 3 in MPT assays were 11.14, 5.02, and 4.24 Iu/ml, whereas the obtained results of PSPT assays were 10.32, 4.11, and 3.06 Iu/ml, respectively. The correlation of MPT and PSPT results was 0.807. The findings of the present study demonstrated a significant correlation between MPT and PSPT results. The implementation of PSPT was more advantageous, compared to MPT due to its ethical approaches and less variability in results. The PSPT is a promising alternative method for intracerebral challenge. However, additional validation is needed to support the establishment of this method.

Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity.

BACKGROUND AND AIM: Recent studies have reported beneficial effects of specific probiotics on obesity. However, the difference in the anti-obesity effects of probiotics as single species and dual species is still uncertain. Therefore, we aimed to compare the efficacy of single and dual species of bacteria on markers of obesity in high-fat diet-induced obese rats. METHODS AND RESULTS: A total of 40 male Sprague-Dawley rats were assigned to one of five groups of varying diets as follows: standard diet, high fat diet (HFD), HFD supplemented with Lactobacillus casei strain Shirota, HFD supplemented with Bifidobacterium longum and HFD supplemented with a mixture of these two bacterial species. After 15 weeks of supplementation, the animals were examined for changes in body weight, body fat, total count of bacteria in fecal, blood serum lipid profile, leptin, adiponectin and inflammatory biomarkers. Histological analysis of the liver and adipose tissue was performed and the hepatic mRNA expression levels of genes related to lipid metabolism were measured. It was found that probiotic supplementation of either B. longum or a mixture of B. longum and LcS bacteria significantly reduced weight and triglycerides in the HFD groups. Supplementation of B. longum bacteria showed better results in terms of modulating leptin level, fat mass, adipocyte size and lipoprotein lipase expression, as well as increasing adiponectin and peroxisome proliferator-activated receptors-γ expression compared to dual species of bacteria. No significant differences were observed in the total count of fecal bacteria, glucose and inflammatory biomarker levels between supplemented groups. CONCLUSIONS: B. longum supplementation in obesity was more beneficial in metabolic profile changes than the mixture species.

The Comparison of Biodistribution, Efficacy and Toxicity of Two PEGylated Liposomal Doxorubicin Formulations in Mice Bearing C-26 Colon Carcinoma: a Preclinical Study.

BACKGROUND: Over the past several years, the considerable attention has been progressively given to liposomal formulations of anthracyclines. SinaDoxosome(®) (Exir Nano Sina Company, Iran) is a pegylated liposomal doxorubicin (DOX) which approved by Food and Drug Administration of IRAN for treatment of some types of cancer. The aim of this study was to compare the biodistribution, efficacy, cardiotoxicity and hepatotoxicity of SinaDoxosome(®) with Caelyx(®) in mice bearing C-26 colon carcinoma. METHODS AND RESULTS: Mice tumor size evaluation during the experimental period (28 days) showed comparable therapeutic efficacy of nano-formulations. The biodistribution studies showed no significant difference in DOX tissue concentration between Caelyx(®) and SinaDoxosome(®). DOX induced-ECG changes were not detected in nano-formulations. No significant alteration was found in biochemical indexes of myocardial injury in mice exposed to nano-formulations in comparison with control mice. The tissue oxidative parameters such as lipid peroxidation, glutathione, catalase and superoxide dismutase was significantly changed as the results of free DOX treatment. However, the oxidative status of Caelyx(®) and SinaDoxosome(®) treated animals did not showed any changes. The experiment also revealed that apoptotic pathway was not activated in the heart of mice exposed to nano-formulations. CONCLUSIONS: Although this investigation showed that Caelyx(®) and SinaDoxosome(®) are similar in terms of biodistribution, efficacy and toxicity, appropriate clinical evaluations in patients should be considered.

Effects of combined therapy with silymarin and glucantime on leishmaniasis induced by Leishmania major in BALB/c mice.

Leishmania major is resistant to the traditional treatments in many parts of the world. PgpA, a member of (ABC) transporter superfamily, has been identified in Leishmania involved in antimony resistance. Silymarin can inhibit PgpA. The aim of this study was to determine the effect of combined therapy with glucantime and silymarin on Cutaneous Leishmaniasis. The effects of silymarin on response of L. major to glucantime were evaluated with amastigote macrophage and mice model of leishmaniasis. Immediately after injection in mice inoculated into footpads with L. major amastigote, systemic treatment was performed and the size of footpad swelling was measured twice a week. 4 and 8 weeks after the beginning of the treatment, splenic parasite burden was done. Silymarin showed no significant effect on the response of L. major promastigotes to glucantime. 2 formulations (glucantime 25 µm with silymarin 25 µm or 12.5 µm) reduced cell death in amastigote assays. The effect of silymarin on footpad swelling was detected when the combination of low-dose glucantime (20 mg/kg) with 25-50 mg/kg silymarin (especially 50 mg/kg) were used at day 22 of post infection (P<0.05). According to the parasite burden data, use of silymarin in the presence of different doses of glucantime, did not show significant effect compared to glucantime alone. The results of this study suggest that silymarin in conjunction with glucantime may have benefit effects in murine model of cutaneous leishmaniasis.

Evaluation of anticonvulsant effect of two novels 4-[1-(4-fluorobenzyl)- 5-imidazolyl] dihydropyridine derivatives in mice.

In this study the anticonvulsant effect of two dihydropyridine derivatives [diethyl -1,4- dihydro -2,6-dimethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (A) and diethyl -1,4-dihydro -2,6- diethyl -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat (B)] by pentylenetetrazole (PTZ) and electroshock in mice was evaluated. The latency and HLTE (hind limb tonic extensions), the duration of HLTE and the mortality protection in pentylenetetrazole test and the HLTE duration in electroshock test were assessed. Both compounds had significant differences with negative control in all doses used. There was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) in the starting point of HLTE and between nifedipine andA(62.2 and 108.9 mg/kg doses) in the duration of HLTE in the PTZ test. Also, there was no significant difference between nifedipine and B (96.7 and 169.2 mg/kg doses) andA(62.2 and 108.9 mg/kg doses) in electroshock test. All doses ofAand B and nifedipine showed less effect than phenytoin and valproate. This study showed that bothAand B have anticonvulsant activity in the PTZ-induced seizure model and the MES test. These compounds, thus, might be useful in the petit mal and grand mal epilepsy.

Protective effects of aqueous and ethanolic extracts of Nigella sativa L. and Portulaca oleracea L. on free radical induced hemolysis of RBCs.

BACKGROUND AND THE PURPOSE OF THE STUDY: It has been shown that Nigella sativa L. and Portulaca oleracea L. have many antioxidant components. In the present study, the cytoprotective effect of ethanolic and aqueous extracts of N.sativa and P.oleracea against hemolytic damages induced by free radical initiator, AAPH [2, 2' azobis (2- amidinopropane) hydrochloride] was evaluated. METHODS: Hemolysis was induced by addition of AAPH. To study the cytoprotective effect, aqueous (50, 200, 300, 400, 800 µg/ml) and ethanolic (25, 100, 150, 200 and 400 µg/ml) extracts of N. sativa and aqueous (25, 50, 100, 150, 200 and 400 µg/ml) and ethanolic (300, 600, 900, 1200 and 1800 µg/ml) extracts of P. oleracea were employed. RBCs were incubated with both extracts and AAPH at 37 °C for 6 hrs. In order to evaluate the impact of the time of addition, extracts were added one and 2 hrs after AAPH. Samples of suspensions were removed at different times and the degree of hemolysis was assessed spectrophotometrically by reading the absorption of supernatants at 540 nm. RESULTS: Aqueous (300, 400 and 800 µg/ml) and ethanolic (150, 200 and 400 µg/ml) extracts of N.sativa and also, aqueous (100, 150, 200 and 400 µg/ml) and ethanolic (1200, 1800 µg/ml) extracts of P.oleracea showed concentration-dependent cytoprotective effects. Addition of extracts one hour after AAPH reduced but did not eliminate protective activities of extracts. CONCLUSION: Cytorotective effect of aqueous and ethanolic extracts of N. sativa and P. oleracea against AAPH- induced hemolysis may be related to antioxidant properties of these plants.

Immunotoxicity of paraquat after subacute exposure to mice.

The immunotoxic effect of paraquat (PQ), a herbicide that has been used widely in agriculture was investigated using Balb/c mice. Paraquat was administered at doses of 1, 0.1, and 0.01 mg/kg for 21 days. Body weight, organ weight, cellularity of spleen, delayed type of hypersensitivity (DTH) response, plaque-forming cell (PFC) assay, hemagglutination titer (HA), quantitative hemolysis of SRBC (QHS) assay, spleen cell subtypes, cytokine production and lymphocyte proliferation assay were studied in various groups of animals. Results showed that high dose of PQ (1mg/kg) could suppress both cellular and humoral activity of the immune system. PQ at medium dose (0.1 mg/kg) did not show any changes in organ weight, body weight and spleen cellularity but significantly decreased the proliferation response to PHA and the production of IFNgamma. PQ at low dose (0.01 mg/kg) did not produce any significant changes in humoral or cellular responses of the immune system. In conclusion, paraquat at high dose has an inhibitory effect on the cell-mediated and humoral immunity. It seems that PQ has no adverse effects on mice immune system at low doses of 0.01 mg/kg, which is two times the PQ allowed daily intake (ADI) limit.

Evaluation of effect of silymarin on granulosa cell apoptosis and follicular development in patients undergoing in vitro fertilization

To investigate the effects of silymarin on follicular development, we enrolled 40 healthy women undergoing in vitro fertilization [IVF] due to male factor infertility in this trial. They underwent ovulation induction and on a random and blind basis, patients were assigned to receive silymarin [70 mg X 3/day] or placebo from the beginning of the induction cycle. The number and quality of oocytes retrieved were evaluated and apoptosis of granolusa cells was studied. There was no significant difference between the groups for mean number of follicles >/= 18 mm [P = 0.131], mean number of oocytes retrieved [P = 0.209] or endometrial thickness [P = 0.673]. However, the proportion of total apoptosis in the study group was significantly lower than in the placebo group [P = 0.032]. These data suggest that administration of silymarin in IVF patients concomitantly with gonadotropin results in reduction of granolusa cell apoptosis but does not have any effect in promotion of follicular development, oocyte retrieval or endometrial thickness