The effect of royal jelly and silver nanoparticles on liver and kidney inflammation.

OBJECTIVE: Royal jelly (RJ) is a honey bee product for which, anti-inflammatory properties were shown in vitro. Nanoparticles, including nano-silver (NS), are plausible inflammation inducers that act by activation of immune cells and consequent production of pro-inflammatory cytokines. This project aimed to explore immunomodulatory effects of royal jelly and nano-silver on the kidney and liver. MATERIALS AND METHODS: In this project, 40 male rats were grouped as follows: 10 rats as controls, 10 rats treated with RJ; 10 rats treated with both NS and RJ and 10 rats treated with NS. Liver and kidney interleukin (IL)-1ß, -2, -6, and -33 levels were determined using commercial ELISA kits. RESULTS: RJ reduced kidney IL-6 levels in comparison to control and NS--RJ groups. RJ and NS reduced kidney and liver IL-1ß levels. Kidney IL-33 levels were decreased in the RJ and nano-silver groups in comparison to the NS--RJ group. CONCLUSION: Based on this study, it may be concluded that RJ together with NS can play anti-inflammatory roles and may affect the function of immune cells.

Investigation of grape sap on wingless/integrated and ß-catenin genes expression with histological factors on the hair follicle in rat.

BACKGROUND AND PURPOSE: Natural products are used to improve the damage caused by harmful reagents in various pathological situations. This study investigated the effect of grape sap as a natural product with antioxidant properties on follicle cell proliferation in bleomycin (as a chemotherapy agent with toxic effects on hair growth) treated rats skin. EXPERIMENTAL APPROACH: The bleomycin treated rats were administrated grape sap. Wingless/integrated (wnt) and ß-catenin gene expression as follicle proliferative markers were evaluated using real-time polymerase chain reaction. Furthermore, histological factors and total antioxidant capacity were evaluated. FINDINGS / RESULTS: The data showed that, grape sap increased the number of anagenic hair follicle in grape sap (100 mg/kg) group (P < 0.001), sebaceous glands (P < 0.001), blood vessel density (P < 0.001), and hair growth length (P < 0.001). Also, wnt and ß-catenin gene expression was elevated. The data showed that wnt and ß-catenin gene expression were elevated in grape sap treated animals versus bleomycin group (P < 0.01 and 0.001, respectively). CONCLUSION AND IMPLICATIONS: Our finding showed that grape sap can be effective in increasing hair growth a gains bleomycin toxic effects on skin hair growth.

Transient brain hypothermia reduces the reperfusion injury of delayed tissue plasminogen activator and extends its therapeutic time window in a focal embolic stroke model.

It has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether shortIt has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether short-term and mild local brain cooling can prevent hyperemia and/or adverse effects of delayed tPA in rat embolic stroke model. Male animals were subjected to embolic stroke and then randomly classified into control (saline), tPA (1mg/kg; i.v.), local hypothermia (LH), and tPA+LH. The drug was injected at 6 h after ischemia. LH was conducted by direct ipsilateral (injured) hemisphere cooling at 6.5h after stroke and maintained for approximately 30min. Cerebral blood flow was monitored in duration of 60 minute after tPA administration and hyperemic response was measured. Infarct volume, blood-brain barrier (BBB) disruption, edema formation, neurological deficits, and matrix metalloproteinase-9 (MMP-9) level were measured 48 h later. A combination of tPA+LH significantly diminished infarct volume in comparison with the tPA (P< 0.001) and control (P<0.05) groups. Combination therapy also decreased BBB leakage (P<0.001), MMP-9 level or edema (P<0.05) and improved neurological functions at 24 and 48h after stroke. LH caused a gradual decrease in hyperemic response after thrombolysis compared to the control (P<0.05) or tPA (P<0.001) groups. LH alone also reduced infarct volume, BBB leakage or edema (P<0.05). The short-term local brain hypothermia may mitigate reperfusion injury following delayed tPA therapy and extend its time window up to 6h.

The expression of HoxB5 and SPC in neonatal rat lung after exposure to fluoxetine.

OBJECTIVE: Approximately 10% of pregnant women suffer from pregnancy-associated depression. Fluoxetine, as a selective serotonin reuptake inhibitor, is being employed as a therapy for depressive disorders. The present study aimed to determine the effects of fluoxetine on neonatal lung development. METHODS: Thirty pregnant Wistar rats (weighing 200-250 g) were treated daily with 7 mg/kg fluoxetine from gestation day 0 to gestation day 21, via gavage. The control group received a similar volume of distilled water only. Following delivery, the newborns and their lungs were immediately weighed in both of the groups. The right lung was fixed for histological assessments while the left lung was used for evaluation of the expression of SPC and HoxB5 by the real-time polymerase chain reaction method. RESULTS: Results have indicated that even though the body weight and the number of neonatal rats in both groups were the same, the lung weight of neonates exposed to fluoxetine was significantly different compared to the control group (P<0.05). Expression of both genes was increased, nonetheless, only elevation of HoxB5 was significant (P<0.05). Histological studies demonstrated that lung tissue in the fluoxetine treatment group morphologically appears to be similar to the pseudoglandular phase, whereas the control group lungs experienced more development. CONCLUSION: According to the upregulated expression of HoxB5 concerning histological findings, results of the present study showed that fluoxetine can influence lung growth and may in turn lead to delay in lung development. So establishment of studies to identify the effects of antidepressant drugs during pregnancy is deserved.

The Persian Version of a Participation Scale: Is It Valid and Reliable Enough for Use among Iranian Patients with Multiple Sclerosis?

BACKGROUND AND PURPOSE: The aim of this study was to determine the face and criterion validity, stability reliability, and internal consistency of the Persian version of the Impact on Participation and Autonomy (IPA-p) scale among Iranian people with multiple sclerosis (MS). METHODS: Trained experts interviewed 364 MS patients and their relatives to assess the criterion validity, stability reliability, and internal consistency of the IPA-p scale. Ten specialists from different disciplines were also recruited to assess its face validity. A consent form was completed by the patients and their relatives. Internal consistency reliability was measured using Cronbach's alpha and stability reliability was assessed using interclass correlation coefficients (ICCs). The test-retest method was used to detect the reliability of the questioner. The study subjects completed the IPA-p scale on two occasions separated by an interval of 30-45 days. Study checklists were also used to assess the face validity, stability reliability, and internal consistency of the IPA-p scale. RESULTS: About 50% of the respondents reported their perceived overall participation to be "good" or "very good" and 60% of the specialists rated the ability of the IPA-p scale to measure what it was designed for as "excellent." Spearman correlation coefficients were >0.8 for all but one IPA-p domain. Cronbach's alpha between the mean IPA-p scale scores achieved on two separate occasions ranged from 0.858 to 0.913. The highest and lowest internal consistencies belonged to the "social relationships" and "education and learning" domains, respectively. The test-retest ICCs for the nine domains were between 0.789 and 0.919, and all were significant at p<0.001. CONCLUSIONS: The IPA-p questionnaire can be considered a valid and reliable instrument for assessing self-reported participation among Iranian MS patients.

Effect of aqueous extract of Achillea millefolium on the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.

OBJECTIVE: Achillea millefolium (A. millefolium) is widely used as an anti-inflammatory remedy in traditional and herbal medicine. In this study, we investigated the effect of an aqueous extract from A. millefolium on experimental autoimmune encephalomyelitis (EAE) and on the serum cytokine levels in C57BL/6 mice. MATERIALS AND METHODS: EAE was induced in 63 C57BL/6 mice weighing 20-25 g (8 weeks old). Following immunization, the treatment protocol was initiated by using different doses of an aqueous extract from A. millefolium (1, 5, and 10 mg/mouse/day). Histopathologic assessments were performed by hematoxylin and eosin (H and E) and luxol fast blue (LFB) staining. Behavioral disabilities were recorded by a camera. Serum levels of interleukin (IL)-10, IL-12, and transforming growth factor (TGF)-ß were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: On average, mice developed classical behavioral disabilities of EAE, 13.2 ± 1.9 days following immunization. Treatment of mice with A. millefolium led to delay the appearance of behavioral disabilities along with reduced severity of the behavioral disabilities. Treatment with A. millefolium prevented weight loss and increased serum levels of TGF-ß in immunized mice with MOG35-55. EAE-induced mice, which were treated with A. millefolium, had less cerebral infiltration of inflammatory cells. CONCLUSION: The results demonstrated that treatment with aqueous extract of A. millefolium may attenuate disease severity, inflammatory responses, and demyelinating lesions in EAE-induced mice. In addition, following treatment with A. millefolium, serum levels of TGF-ßwere increased in EAE-induced mice.

Proinflammatory cytokines in the embolic model of cerebral ischemia in rat.

Increased levels of proinflammatory cytokines have been recorded after the onset of transient or permanent brain ischemia and are usually associated with exacerbation of ischemic injury. Embolic stroke model is more relevant to the pathophysiological situation in such patients, because the majority of ischemic injuries in humans are induced by old thrombi that originate from the heart and carotid arteries. Therefore, the aim of the present study was to investigate changes of inflammatory cytokines after embolic stroke. Rats were subjected to embolic stroke, induced by a natural old clot which was injected in Middle Cerebral Artery (MCA), or sham stroke, which the same volume of saline was injected into the MCA. At 48 h after stroke induction, the levels of 5 cytokines (IL-1α and ß, IL-6, IFN-γ and TNF-α) were determined in 500 µg of total protein using the Bio-Plex Rat Cytokine Array (BioRad), according to the manufacturer's instructions in ischemic and non-ischemic cortices. While stroke animals showed infarctions and neurological deficits, we did not observe any cerebral infarction and neurological deficits in sham-operated animals. The levels of IL-1α (p=0.000) and -ß (p =0.004), IL-6 (p =0.008), TNF-α (p =0.000) and IFN-γ (p =0.044) were significantly increased compared to sham treated animals. The findings of the present study suggest that part of ischemic injury in the embolic stroke may be mediated through the increased levels of inflammatory cytokines.

Coexistence of multiple arterial variations in the genitourinary system.

Variations in the renal, adrenal and testicular arteries are of clinical significance as well as anatomical and embryological interest. The present case report describes the incidental finding of unilateral multiple renal arteries on the right side with bilateral variant testicular arteries, which had not been reported so far. These variations were observed during routine dissection of the abdominal region in an Iranian cadaver. The upper supplementary renal artery branched from the abdominal aorta and sent superior suprarenal artery to the adrenal gland. The lower supplementary renal artery arose from the main renal artery. Both additional arteries entered the kidney proximal to its hilum. The right testicular artery supplied the right suprarenal gland by an unusual branch. Double testicular arteries were seen on the left side with a relatively high origin from abdominal aorta. The objective of this report is to supplement the knowledge of vascular variations in the renal, suprarenal and testicular arteries that could be quite useful from a clinical point of view.

Lack of significance of the BRCA2 promoter methylation status in different genotypes of the MTHFR a1298c polymorphism in ovarian cancer cases in Iran.

OBJECTIVE: Promoter methylation, which can be regulated by MTHFR activity, is associated with silencing of genes. In this study we evaluated the methylation status (type) of the BRCA2 promoter in ovarian cancer patients carrying different genotypes of the MTHFR gene (A or C polymorphisms at position 1298). METHODS: The methylation type of the BRCA2 promoter was evaluated using bisulfate-modified DNA in methylation- specific PCR and the MTHFRa1278c polymorphism was assessed by PCR-RFLP. RESULTS: Analysis of the BRCA2 promoter methylation type of cases showed that 7 out of 60 cases (11.7%) were methylated while the remaining 53 (88.3%) were unmethylated. In methylated cases, one out of the 7 cases had a CC genotype and the remaining 6 methylated cases had an AC genotype. The AA genotype was absent. In unmethylated cases, 34, 18, and one out of these had AC, AA and CC genotype, respectively. CONCLUSION: There was no significant relationship between the methylation types of the BRCA2 promoter in different genotypes of MTHFRa1298c polymorphism in ovarian cancer; p=0.255. There was no significant relation between the methylation types of the BRCA2 promoter in different genotypes of the MTHFRa1298c polymorphism in ovarian cancer.

Evaluation of effects of methamphetamine repeated dosing on proliferation and apoptosis of rat germ cells.

Methamphetamine (MAMP) is a central nervous system stimulant that is increasingly abused especially by teenagers and young adults, a group in its reproductive age. MAMP effects on the male reproductive system are not clear. In this experimental study, we evaluated the effects of MAMP administration on proliferation and apoptosis in seminiferous tubules of rat testis. Methamphetamine hydrochloride was synthesized by iodination of norephedrine hydrochloride and reduction to methamphetamine. Mature male rats were randomly divided into four groups (n=7) and were injected intraperitoneally with MAMP (1, 5 or 10 mg/kg) or saline at the same time, once daily for 14 consecutive days. Twenty four hs after the last injection, perfused testis were fixed, sectioned and stained by TUNEL labeling or proliferating cell nuclear antigen (PCNA) immunostaining. Apoptotis and proliferation indices were calculated and ratios of proliferation/apoptosis in the seminiferous tubules were obtained. Cell proliferation and the ratio of proliferation to apoptosis decreased significantly in all experimental groups compared to the control group. Conversely, apoptosis was increased in these groups. Such differences were observed in both spermatogonia and primary spermatocytes. In the control group, more than 95% of spermatogonia were PCNA-positive. However, 10 mg/kg of MAMP caused a reduction to approximately 75% PCNA staining in spermatogonia. In some tubules of the experimental groups, more than 10 TUNEL-positive germ cells were seen, although in the control group, the tubules with 3 TUNEL-positive germ cells were rarely observed and the majority of tubules were without such cells. There were significant differences in the indices between the 1 mg/kg group and the higher dose groups, but there was no such difference between the 5 mg/kg and 10 mg/kg groups. In some tubules of the experimental groups, significant gaps in the epithelium between the spermatogonia layer and other cell layers were observed. These results show that repeated administration of MAMP, especially at higher doses, may cause a decrease in cellular proliferation, induce apoptosis and change the proliferation/apoptosis ratio in testis. This might explain the MAMP effect on the spermatogenesis process. It is suggested that studies on the consequence of MAMP consumption on male fertility is warranted.