Protective role of ellagic acid and taurine against fluoxetine induced hepatotoxic effects on biochemical and oxidative stress parameters, histopathological changes, and gene expressions of IL-1ß, NF-κB, and TNF-α in male Wistar rats.

PURPOSES: Hepatic bioactivation of fluoxetine (FXN) could increase free radicals' generation provoking hepatotoxicity. Therefore, the protective effects of ellagic acid (EA) and taurine (TAU) treatments against fluoxetine-induced liver damage in rats were examined. MATERIALS AND METHODS: Sixty four male Wistar rats were randomly assigned to 8 groups (n = 8). Group (1) Control, group (2) FXN, group (3) FXN + EA, group (4) FXN + TAU, group (5) FXN + EA + TAU, group (6) EA, group (7) TAU, and group (8) EA + TAU. Then, the serum and tissue parameters of the oxidative stress were examined. KEY FINDINGS: FXN significantly raised serum MDA, protein carbonyl, lipid profile, ALT, AST, ALP, total bilirubin, serum IL-1ß; and gene expressions of IL-1ß, NF-κB, and TNF-α. Moreover, it significantly decreased HDL-C, ferric reducing antioxidant power (FRAP), catalase activity, vitamin C, and SOD activity in the liver compared to group 1. When compared to group 2, EA and TAU treatment dramatically increased antioxidant capacity and lowered hepatotoxic biochemical markers and cellular inflammation. Results also showed a protective effect of treatment against oxidative damage caused by hepatocytes' cytoarchitecture. SIGNIFICANCE: Our study concluded the beneficial effects of EA and TAU on FXN-induced hepatotoxicity. These effects were derived from free radical scavenging properties and the anti-inflammatory effects related to IL-1ß, NF-κB, and TNF-α gene expression inhibition.

Evaluation of S100A12 and Apo-A1 plasma level potency in untreated new relapsing-remitting multiple sclerosis patients and their family members.

Multiple sclerosis is an inflammatory disease of the spinal cord and brain. Receptor for advanced glycation end products and Apolipoprotein A1 (Apo-AI) have been recommended to have a pathogenic role in the neuroinflammatory disorder as multiple sclerosis. The purpose of this research was to measure the plasma levels of S100A12 and Apo-A1 in the first-degree family of relapsing-remitting multiple sclerosis (RRMS) patients. Plasma levels of S100A12 & Apo-A1 were evaluated via enzyme-linked immunosorbent assay in the thirty-five new cases of untreated patients with deterministic RRMS according to the McDonald criteria, twenty-four healthy controls, and twenty-six first-degree members of untreated RRMS patients (called them as high-risk group). The main findings of this study were as follows: the plasma level of S100A12 was significantly lower in the new cases of untreated RRMS (P ≤ 0.05; 0.045) and high-risk (P ≤ 0.05; 0.001) groups. Although the plasma protein level of Apo-A1 was reduced significantly in the high-risk group (P < 0.05, P = 0.003) as compared to the healthy control group, there was no significant difference in the untreated RRMS patients (P = 0.379). The plasma level of vitamin D3 in both RRMS patients and high-risk groups displayed significance reduction, although, there was no significant association between vitamin D and S100A12 & Apo-A1 levels. Given the role of S100A12 and Apo-A1 in the inflammatory process performed in the first-degree family members of the RRMS patients, which revealed a significant decrease in this group, we concluded that they can be considered as one of the contributing factors in the pathogenesis of MS, though more research is needed before assuming them as predictive biomarkers.

Methamphetamine Downregulates the Sperm-Specific Calcium Channels Involved in Sperm Motility in Rats.

Calcium channels play essential roles in sperm motility. A family of sperm-specific cation channels including CatSper1-4 has been identified as voltage-dependent ion channels that act as sperm motility regulators. Methamphetamine is known to cause apoptosis in seminiferous tubules and affect sperm quality. This research was conducted to investigate the effects of methamphetamine on expression of the CatSper family and Mvh genes. Thirty-six adult Wistar rats were divided into four groups of nine rats each: the control and experimental groups 1, 2, and 3. The control group received no solvents or drugs, but experimental groups 1, 2, and 3 were daily given 0.2 mL of a solution by gavage that contained 0.5, 1, and 2 mg of methamphetamine, respectively, for 45 days. The rats were then anesthetized, and one testis removed from each rat was used in a reverse transcription-polymerase chain reaction (RT-PCR). Analysis of variance (ANOVA) and Tukey's posthoc test were used to analyze the data at the P < 0.05 significance level. Treatment with methamphetamine resulted in decreased testis and epididymis weights compared to the control rats. The results showed that the mRNA fold expression level of the CatSper family and Mvh genes decreased significantly in experimental groups compared to that in the control (P < 0.05). Methamphetamine decreased the expression levels of the CatSper and Mvh genes, and thus, it seemed that it can increase the probability of infertility through sperm motility reduction by lowering the expression levels of these genes.

Diverse Effect of Vitamin C and N-Acetylcysteine on Aluminum-Induced Eryptosis.

PURPOSE: The role of oxidative stress in Aluminum (Al)-induced apoptotic effects has been investigated and suicidal death of erythrocytes, eryptosis, is characterized by cell shrinkage and phosphatidylserine externalization (PSE) at the surface of the erythrocyte cell membrane. Eryptosis is stimulated by an increase in cytosolic Ca2+ concentration and reactive oxygen species (ROS). This ex vivo study was conducted to evaluate the effect of well-known antioxidants including vitamin C (vit C) and N-acetylcysteine (NAC), against Al-induced hemolysis and eryptosis. METHODS: Isolated erythrocytes from the healthy volunteers were partitioned into various groups (6 replicates/group) and treated by various concentrations of Al (3-100 µM) in the presence and absence of vit C (0.6 mM) and NAC (1 mM). After 24 hours of treatment, hemolysis was determined from hemoglobin levels in the supernatant. Flowcytometric methods were applied to measure PSE, cell shrinkage, Ca2+ content, and ROS abundance using annexin V-binding, forward scatter, Fluo3-fluorescence, and DCFDA dependent fluorescence, respectively. Reduced glutathione (GSH) was measured by the ELISA method. RESULTS: The results showed that a 24 hours' exposure of the erythrocytes to Al (10-100 µM) significantly increased hemolysis in a dose and Ca2+dependent manner. Al also dramatically decreased forward scatter. The percentage of PSE cells, Fluo3-fluorescence, and DCFDA fluorescence were increased by Al. Furthermore, cotreatment with NAC inhibited the effect of Al on hemolysis, eryptosis, and ROS production. Vit C decreased Al-induced ROS production. However, increased Al-induced eryptosis. There were no significant changes in glutathione after the ALCL3 treatment. CONCLUSIONS: Al-induced eryptosis and hemolysis through triggering oxidative stress, while NAC could diverse this effect. In contrast, vit C might intensify Al-induced eryptosis at particular doses through a less known mechanism.

Investigation of Decitabine Effects on HDAC3 and HDAC7 mRNA Expression in NALM-6 and HL-60 Cancer Cell Lines.

BACKGROUND: Decitabine is a potent anticancer hypomethylating agent and changes the gene expression through the gene's promoter demethylation and also independently from DNA demethylation. So, the present study was designed to distinguish whether Decitabine, in addition to inhibitory effects on DNA methyltransferase, can change HDAC3 and HDAC7 mRNA expression in NALM-6 and HL-60 cancer cell lines. METHODS: HL-60, NALM-6, and normal cells were cultured, and the Decitabine treatment dose was obtained (1 µM) through the MTT assay. Finally, HDAC3 and HDAC7 mRNA expression were measured by Real-Time PCR in HL-60 and NALM-6 cancerous cells before and after treatment. Furthermore, HDAC3 and HDAC7 mRNA expression in untreated HL-60 and NALM-6 cancerous cells were compared to normal cells. RESULTS: Our results revealed that the expression of HDAC3 and HDAC7 in HL-60 and NALM-6 cells increases as compared to normal cells. After treatment of HL-60 and NALM-6 cells with Decitabine, HDAC3, and HDAC7 mRNA expression were decreased significantly. CONCLUSION: Our data confirmed that the effects of Decitabine are not limited to direct hypomethylation of DNMTs, but it can indirectly affect other epigenetic factors, such as HDACs activity, through converging pathways.

Effect of Prolonged Infusion of Alamandine on Cardiovascular Parameters and Cardiac ACE2 Expression in a Rat Model of Renovascular Hypertension.

Alamandine is a new member of the angiotensin family. Here, we studied the mRNA and protein expression of cardiac angiotensin-converting enzyme 2 (ACE2) in the chronic phase of a rat model of 2-kidney, 1-clip hypertension (2K1C), and the effects of 2-week alamandine infusion on blood pressure, cardiac indices, and ACE2 mRNA and protein expression in the hearts. The rats were subjected to to sham-operation or placement of plexiglass clips around the left renal artery. Alamandine, at a dose of 600 µg/kg/d, was administered for 2 weeks via an osmotic mini-pump. At 18 weeks, after induction of hypertension, blood pressure and cardiac indices of contractility were measured using a Powerlab Physiograph system. The ACE2 mRNA and protein levels were determined using real time-PCR and Western blotting, respectively. In the hypertensive rats, alamandine caused a significant decrease in systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), left ventricular end-diastolic pressure (p < 0.001) and, left ventricular systolic pressure (p < 0.001) and increase in the maximum rate of pressure change in the left ventricle (dP/dt(max)) (p < 0.05). Also, the ACE2 mRNA expression in the heart increased in the hypertensive rats compared to the normotensive rats (p < 0.05), and alamandine restored this to normal values, although these changes were only seen at the mRNA and not the protein level. Histological analysis of cardiac tissue confirmed that alamandine decreased cardiac fibrosis and hypertrophy in 2K1C hypertensive rats. Our results indicate that alamandine, which acts as a depressor arm of the renin-angiotensin system, could be developed for treating hypertension.

SCSA results correlated with rate of motility reduction after ejaculation in Asthenozoospermia.

Maintaining sperm motility after ejaculation is important for fertilisation. Apoptosis may play an important role to reduce sperm motility after ejaculation. The aim of this study was to perceive whether or not an increase in apoptosis reduces sperm motility in a higher degree after ejaculation and whether it can be predicted by laboratory tests, such as sperm chromatin structure assay (SCSA). Fifty-one Asthenozoospermia and 20 fertile subjects participated in this study. SCSA was applied using flow cytometry. Fluorescein-labelled inhibitors of Caspases (FLICA) method was used for assessment of active Caspase-3. Motility was assessed every 2 hr after ejaculation for 12 hr. Both SCSA and spermatozoa with active Caspase-3 were significantly correlated with the rate of motility reduction after ejaculation. In the subgroups who had SCSA <27% and active Caspase-3 <40%, the sperm motility reduction significantly occurred 6-8 hr after ejaculation compared to the fresh sample. In the cases of SCSA ≥27% and active Caspase-3 ≥ 40%, a significant decrease in motility was observed between 2 and 4 hr after ejaculation. The result demonstrated a significant trend in the rate of sperm motility reduction with SCSA increase, which suggests SCSA may indirectly show a good scheme of apoptosis status and may forecast the rate of motility reduction after ejaculation in Asthenozoospermia.

Exploring needs and expectations of spouses of addicted men in Iran: a qualitative study.

Addiction is one of the major problems that affect everyone in the society especially the spouses of addicted men who have to face a large number of problems which are the consequences of their husband's addiction. This qualitative study was conducted to explore the needs and expectations of women who are living with their addicted husband in Iran. Twenty-four spouses of addicted men participated in this study. The participants were interviewed and each interview was analyzed via the content analysis method. The results of this study showed that the women's difficulties were related to their approach to the treatment, or their husbands' response to the treatment, financial constraints and emotional and informational needs. Moreover, these Iranian women expected more stringent control by the government on the phenomenon of addiction and drug trafficking with a view of having a drug-free country. The needs and expectations of the wives of addicted men are context-based and should be assessed separately between individuals, families, and communities. In addition to the addicted person, it is vitally important that the health of the family members of drug addicts be taken into account and for whom supportive services be provided.

Chronic effect of gabapentin on liver function in adult male rats.

Gabapentin (GPN) is a new antiepileptic agent currently in used as add-on therapy in adult patients suffering from partial seizures. The extent of liver damage at different dosage and long term treatment with GPN is not yet clear. Therefore this study was undertaken to find out the possibility of liver damage by this drug. Adult male (Wistar) rats of 180-220 g were administered intraperitoneally with GPN (20 or 100 mg/kg) for 45 days. After the experimental period, the liver function tests were carried out in control and experimental groups. The activity of liver enzymes, with 20 mg/kg of GPN were not significantly different from the control group but, the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, direct bilirubin and total bilirubin were enhanced significantly with 100 mg/kg of GPN. Total protein and albumin decreased in this group as compared with control animals. The histopathology of the liver parenchymal cells also showed minute foci of necrosis in a few rats treated with high dose of GPN, whereas, at therapeutic dose the histopathology and biochemical indices showed almost normal values. At therapeutic dose GPN is a safer drug with regards to liver function and hepatocellular damage as compared with other antiepileptic drugs.

Effect of Ramadan fasting in tropical summer months on ocular refractive and biometric characteristics.

BACKGROUND: Islamic Ramadan is the month of fasting, in which intake of food and drink is restricted from sunrise until sunset. The objective of the present study was to find out the effect of altered eating habits during Ramadan fasting on ocular refractive and biometric properties. METHODS: In this prospective case series, 40 eyes of 22 healthy volunteers with a mean age of 60.55 ± 12.20 years were enrolled. Patients with any systemic disorder and eyes with pathology or previous surgery were excluded. One month before Ramadan (at 8.00 am), during Ramadan fasting (at 8.00 am and 4.00 pm) and one month later during the non-fasting period (at 8.00 am), ocular refractive and biometric characteristics were measured using an autokeratorefractometer (Auto-Kerato-Refractometer KR-8900; Topcon Co, Tokyo, Japan) and contact ultrasonic biometry (Nidek Echoscan US 800; Nidek Co, Tokyo, Japan). RESULTS: Anterior chamber depth was significantly increased during fasting compared with baseline measurements and returned to baseline one month after Ramadan (3.22 ± 0.07 mm and 4.33 ± 0.17 mm for non-fasting and fasting, respectively; p < 0.001). The anterior chamber depth measurements were significantly larger at 8.00 am during fasting compared with 4.00 pm (p = 0.01). Axial length was significantly decreased during fasting and returned to baseline one month after Ramadan (23.09 ± 0.14 mm and 22.65 ± 0.18 mm, for non-fasting and fasting, respectively; p < 0.001). Intraocular lens power calculations were significantly increased during fasting and returned to baseline one month after Ramadan (SRK-T formula: 21.46 ± 0.27 D and 22.92 ± 0.46 D, for non-fasting and fasting, respectively; p < 0.001). There were no significant differences in spherical equivalent, corneal astigmatism, mean keratometry and flatter and steeper corneal radii of curvature between time intervals. CONCLUSIONS: Ramadan fasting is associated with statistically significant alterations in anterior chamber depth and axial length that result in both statistically and clinically significant changes in intraocular lens power calculations. Therefore, relying on measurements taken during this month might lead to refractive errors after cataract surgery.

Ocular refractive and biometric characteristics in patients with thalassaemia major.

BACKGROUND: Thalassaemia major is associated with characteristic findings in craniofacial bony structures and thereby may render abnormal bony orbit and subsequently distinctive ocular biometry. The purpose of the present study was to evaluate the ocular refractive and biometric characteristics in patients with thalassaemia major. METHODS: This case-controlled study comprised 94 eyes of 47 patients with thalassaemia major and 88 eyes of 44 age- and sex-matched healthy control subjects. All participants had a complete ocular examination including slitlamp biomicroscopy, fundoscopy, ocular biometry, keratometry, refraction and analysis using Fourier transformation. RESULTS: There were no significant differences in spherical equivalent (p = 0.66) and total astigmatism (p = 0.83) between groups. Mean uncorrected vision and visual acuities (logMar) were similar (p = 0.32 and p = 0.71, respectively). Compared with controls, thalassaemic patients had a shorter axial length (23.01 ± 0.12 [SEM] mm versus 23.46 ± 0.12 mm, p = 0.035), thicker crystalline lens (4.01 ± 0.11 mm versus 3.87 ± 0.1 mm, p = 0.046) and steeper average keratometry (44.02 ± 0.24 D versus 43.44 ± 0.24, p = 0.03). Fifty-seven per cent of thalassaemic patients had against-the-rule astigmatism (total), while 64.6 per cent of controls showed a with-the-rule pattern (p < 0.05). These patterns were also found for corneal astigmatism. The magnitudes of total, corneal and lenticular astigmatism were similar among groups. Regression analysis showed significant correlation between corneal (J0 and J45) and total (J0 and J45) astigmatism. The correlations were less prominent between lenticular and total J0 and J45. The mean intraocular pressure was 14.68 ± 0.27 mmHg and 13.3 ± 0.26 mmHg in the thalassaemia and control groups, respectively (p < 0.001). Six eyes (12.8 per cent) of four patients in the thalassaemia group had posterior subcapsular cataract, while the condition had not been observed in controls (p = 0.049). CONCLUSIONS: Shorter axial length, thicker lens, steeper corneal curvature and more against-the-rule pattern were characteristic findings in patients with thalassaemia major.

Post operative voiding efficacy after anterior colporrhaphy.

The aim of this study was to determine the most effective and suitable time to remove the urinary catheter (Foley) after anterior and posterior colporrhaphy surgery. Patients who experience anterior Colporrhaphy operation for genuine stress incontinency or pelvic organ prolapsed will have post operative voiding dysfunction. These patients need postoperative drainage. One of the methods preferred for this purpose is to apply Foley Catheter, but there is no particular regimen available for the exact time of catheter removal in these patients. We have tried to find out the best time to remove Foley catheter after which the repeated Foley catheter is not required or minimized. One hundred and eighty nine patients who have been undergone Colporrhaphy have been selected randomly and divided into three groups' as 1, 2 and 4 days of catheter removal. The number of patients in each group was 62, 63 and 64 respectively. In all three groups, before removing urinary catheter, it was clamped every 4 hrs, for 3 times. After removing of Foley, the patients were guided for urination; the voiding and residual volume was measured. In the patients with an increase of residual volume, the repeated Foley requirement was increased. However, 5.6 % of the patients with residual volume of < or = 33 percent and 23.9% of the patients with residual volume between 33 to 68 percent, and finally 64.8% of the patients with residual volume of > or = 68% had repeated Foley insertion. When considering the number of days, 85, 65 and 35.7 percent of the patients needed repeated Foley after 1, 2, and 4 days of catheter removal respectively. Interestingly, in the third group (4 days of the catheter removal) with residual volume of < or = 33% the repeated Foley requirement was nil, with no increase risk of urinary infection. We suggest that the best time to remove the urinary Foley catheter after anterior and posterior Colporrhaphy is the day four.

Bcl-2 associated athanogene-1 overexpression in diffuse large B-cell lymphoma.

BACKGROUND: Apoptosis and cell cycle regulation play an important role in pathogenesis and tumor progression in patients with Diffuse Large B-Cell Lymphoma (DLBCL). Bcl-2 associated athanogene-1 (BAG-1) is an antiapoptotic protein as well as a regulator of cell growth. There is no conclusive evidence about BAG-1 protein expression in this disease. OBJECTIVE: To investigate the expression level of BAG-1 protein in DLBCL. METHODS: Thirty patients diagnosed from 1997-2004, as having DLBCL, were selected. Also 30 normal lymph nodes were included as normal counterparts in this study. BAG-1 expression was determined by immunohistochemical staining in both DLBCL and normal lymph node samples. RESULTS: Of the 30 DLBCLs examined, 100% were positive for nuclear and 83% were positive for cytoplasmic BAG-1 staining. Of the 30 normal lymph nodes investigated, 20% were positive for nuclear and 0% were positive for cytoplasmic BAG-1 staining. Nuclear staining in DLBCL samples was significantly higher than those of normal lymph nodes (100% versus 20%, p <0.001). Besides, cytoplasmic staining in DLBCL samples was significantly higher than those of normal lymph nodes (83% versus 0%, p <0.001). There was no association between BAG-1 staining and patients' overall survival. CONCLUSION: Our data indicated that BAG-1 protein was deregulated in this disease similar to some other malignancies such as breast and colon cancer. Overexpression of BAG-1 in DLBCL suggests that this protein probably plays an important role in the pathogenesis of DLBCL. Besides, higher nuclear BAG-1 staining might be correlated with poor prognosis.