CARDIOPROTECTIVE EFFECT OF DICHLOROMETHANE VALERIAN (VALERIANA OFFICINALIS) EXTRACT ON ISCHEMIA-REPERFUSION-INDUCED CARDIAC INJURIES IN RATS.

Background: Valepotriate is an active ingredient of valerian (Valeriana officinalis) with strong antioxidant activity that is effective for numerous cardiovascular diseases. Objective: The aim of this study was to investigate the effect of an active ingredient of V. officinalis extract on ischemia-reperfusion-induced cardiac injuries in male rats. Methods: Thirty-two male rats were subjected to ischemia for 40 minutes and reperfusion for five days. The rats were divided into 4 groups of 8 each; group 1 (control) was given normal saline, and groups 2-4 were gavaged with 0.2, 0.1, 0.05 mg/kg of valepotriate extract, respectively, and received extract (0.2 mg/kg ip) two weeks before ischemia induction. Results: Dichloromethane V. officinalis (valepotriate) extract exerted a protective effect against ischemia-reperfusion-induced injuries. So that infarct size and number of ventricular arrhythmia and ventricular escape beats decreased compared to the control group. Moreover, ST segment amplitude, QTC interval, and heart rate decreased in the injured hearts and serum levels of antioxidant enzymes glutathione peroxidase, catalase, and superoxide dismutase increased. Biochemical markers malondialdehyde and lactate dehydrogenase also decreased on day 5 after the onset of reperfusion. Conclusion: V. officinalis extract may have a protective effect against myocardial ischemia-reperfusion by producing antioxidant effects.

A double-blind controlled crossover study to investigate the efficacy of salix extract on primary dysmenorrhea.

OBJECTIVES: Primary dysmenorrhea in the absence of pelvic pathology is a common gynecologic disorder affecting the quality of life of women of reproductive age. This study evaluates the effect of salix extract on primary dysmenorrhea. DESIGN: This study was a randomized crossover clinical trial. SETTING: The study population included 96 female students with level two or three of primary dysmenorrhea: 48 students in the treatment group (sequence I) followed by control (sequence II) and 48 students in control group (sequence I) followed by treatment (sequence II). INTERVENTIONS: The intervention was salix capsule (400 mg daily) and the active control was mefenamic acid capsule (750 mg daily) as. MAIN OUTCOMES: Pain intensity, measured by the visual analog scale (VAS), amount of bleeding, and severity of dysmenorrhea symptoms were outcomes. Generalized estimating equations were used for data analysis. RESULTS: The demographic and menstrual characteristics of the students were homogenous between the groups. The results showed that the students in mefenamic acid group had a significantly higher level of VAS than the students in the salix group over time (1.61 ± 0.06, P < 0.001). The estimated odds of the bleeding level in the salix and mefenamic acid group were not significantly different (P = 0.31). In average, 77.39%±16.18 of the students in salix group showed no symptoms followed by 22.18%±14.08 of the students who experienced mild symptoms. Averagely, 44.58%±20.16 of the students in the mefenamic acid group had mild symptoms followed by moderate symptoms (28.12%±15.29). CONCLUSIONS: Salix extract significantly decreased dysmenorrhea in comparison to mefenamic acid, as the standard treatment of dysmenorrhea.

Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a randomized crossover pilot study.

Hypertension is a major risk factor for cardiovascular disease and has a prevalence of about one billion people worldwide. It has been shown that adherence to a diet rich in fruits and vegetables helps in decreasing blood pressure (BP). This study aimed to investigate the effect of raw beet juice (RBJ) and cooked beet (CB) on BP of hypertensive subjects. In this randomized crossover study, 24 hypertensive subjects aged 25-68 years old were divided into two groups. One group took RBJ for 2 weeks and the other group took CB. After 2 weeks of treatment, both groups had a washout for 2 weeks then switched to the alternate treatment. Each participant consumed 250 ml day(-1) of RBJ or 250 g day(-1) of CB each for a period of 2 weeks. Body weight, BP, flow-mediated dilation (FMD), lipid profile and inflammatory parameters were measured at baseline and after each period. According to the results, high-sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (P<0.05). FMD was significantly (P<0.05) increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-α were significantly (P<0.05) decreased with RBJ or CB. Total antioxidant capacity was increased and non-high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB.

Gender differences in a mouse model of chemotherapy-induced neuropathic pain.

Chemotherapy-induced neuropathic pain is one of the major problems for cancer patients. Although paclitaxel and cisplatin are widely used in women, most laboratory studies of chemotherapy-induced neuropathic pain have been conducted on male animals. The current study examined the gender differences in chemotherapy-induced neuropathic pain in mice. Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) for five consecutive days and cisplatin (1 mg/kg) for seven consecutive days. Cold allodynia was evaluated by measuring the paw withdrawal frequency and duration of paw licking in mice; however, mechanical allodynia was assessed by von Frey filaments. Neuropathic pain began to manifest after a few days (P < 0.001). Cold allodynia was more robust in female mice (P < 0.001) treated with paclitaxel, while no differences were observed between the two genders in the manifestation of paclitaxel-induced mechanical allodynia. Interestingly, no gender differences were observed in cisplatin-induced cold and mechanical allodynia tests. In conclusion, gender differences play a major role in neuropathic pain induced by paclitaxel. The differences between male and female animals should be considered in future studies and the findings should be generalized to humans with caution.

Significance of global versus segmental subclassification of class III and IV lupus nephritis: a single center experience.

INTRODUCTION: Class III and IV are the most ominous among the classes of lupus nephritis (LN) and there are contradictory reports on whether LN class IV-G (global) differs from LN class IV-S (segmental) as envisaged by the International Society of Nephrology and the Renal Pathology Society (ISN/RPS) 2003 classification. These subcategories are not validated for LN class III. This study was designed to assess the differences between global and segmental subclasses in classes III and IV of LN. PATIENTS AND METHODS: In a retrospective analysis, the kidney biopsies of 84 patients with new-onset LN were analyzed. The Student's t-test and Mann-Whitney test were employed to compare differences between the means of continuous variables among the two groups. Fisher's exact test was used to compare the categorical variables. A p-value <0.05 was considered statitistically significant. RESULTS: Of 84 patients, 69 (82.1%) were females and 15 (17.9%) males, with the female to male ratio of 4.6:1. The mean age of all patients was 32.7±12.6 years. The mean serum creatinine at the time of biopsy was 1.5±0.94 mg/dl and the mean urinary protein excretion was 1.6±1.9 g/day. Among 84 biopsies, 26(30.95%) belonged to class III and 37 (44.05%) to class IV LN. In class IV LN, serum creatinine was significantly higher in global vs. segmental subcategory (2.4±1 vs. 1.1±0.5 mg/dl; p=0.034), while. 24-h proteinuria was not significantly different between the subcategories (2.7±1.2 vs. 3.1±1.0 g/d, p=0.56). In LN class III, the mean age, serum creatinine and 24-hour proteinuria did not show significant difference between the global and segmental subcategories (37±17 vs. 30±15 years, p=0.58; 1.2±0.2 vs. 1.25±0.6 mg/dl, p=0.66; 2.03±0.5 vs. 3.1±3.5 g/day, p=0.45, respectively). The proportion of glomeruli showing endocapillary proliferation was significantly higher in global than in segmental subclasses (94.25% vs. 5.72; p=0.026) in class IV LN. The activity and chronicity percent also revealed higher values in global subclass vs. segmental subclass of class IV LN (p=0.038 and p=0.045, respectively). These parameters were not significantly different among the global and segmental subcategories of class III LN (p>0.5 for all parameters). CONCLUSION: In conclusion, our study showed significant differences in renal function and some pathological features on renal biopsies among the global and segmental subclasses of class IV LN. There were no significant differences among these subclasses of class III LN. Further, and larger studies are needed on this subject to substantiate the above results.

Assessing the toxic effects of hydroalcoholic extract of Stachys lavandulifolia Vahl on rat's liver.

AIMS: Stachys lavandulifolia Vahl is a frequently used plant to treat different diseases, but its probable toxic effects have not been reported yet. This study aimed to study the toxicity of the extract on rats' liver. METHODS: In this experimental study, 100 rats were designated into 10 groups and injected normal saline or Stachys lavandulifolia Vahl extract at 50, 100, 150, and 200 mg/kg, intraperitoneally for 28 days. Four case groups and one control group were examined for ALT, AST and ALP after one month and the other groups were evaluated after two months. RESULTS: In the first month, the increase of ALP at all doses and the increase of AST at 200 mg/kg was significant, compared to the control group (p<0.05). In the second month, AST increased at the dosage of 150 mg/kg, and ALP decreased at the dosage of 100 mg/kg, compared to the control group (p<0.05). Histopathological assessment showed a significant dose dependent increase both in necrotic-inflammatory reactions and fibrotic lesions, in the first and second months, compared to the control group (p<0.001). CONCLUSIONS: The Stachys lavandulifolia extract injected intraperitoneally has hepatotoxic effect, which is not eliminated by the drug withdrawal. Therefore, it is necessary to be consumed with caution (Tab. 4, Fig. 1, Ref. 21).

Antioxidant activity and preventive effect of aqueous leaf extract of Aloe Vera on gentamicin-induced nephrotoxicity in male Wistar rats.

OBJECTIVE: In the present study, the nephroprotective and curative effects of aqueous extract of AV on gentamicin-induced tubular toxicity in male Wistar rats were investigated. Antioxidant activity, phenolic and flavonoid contents of AV were also determined. MATERIALS AND METHODS: In a preclinical study, 60 male Wistar rats were designated into 6 groups of 10 and treated as follows: Group I: Treated with vehicle (distilled water) and kept as control. Group II: Received 300 mg/kg/d AV for three days then, AV plus GM (80 mg/kg; intraperitoneally) for 7 more days and sacrificed. Group III: Received 300 mg/kg AV orally for 10 days, then sacrificed. Group IV: Received GM for 7 days and sacrificed. Group V: Received GM for 7 days and saline for ten days and sacrificed on 17th day. Group VI: Received GM for 7 days, then AV for 10 days and sacrificed. RESULTS: The levels of flavonoid and phenolic compounds in Aloe vera extract were 43 ± 3.8 mg/g (Rutin equivalent) and 80.1 ± 3.8 mg/g (Gallic acid equivalent), respectively. The antioxidant activity of the extract was 38%. The intensity of nephrotoxicity in group 2 that received AV 300 mg/kg/d as prophylaxis was not significantly different from the group I and from the group II which treated with 300 mg/kg/d AV without GM. This finding reveals that AV as prophylaxis could potentially attenuate the GM-induced nephrotoxicity. CONCLUSIONS: Aole vera significantly protects the renal cells and reduces the severity of tubular damage caused by gentamicin. However, it cannot regenerate tubular damage.

Residues of oxytetracycline in cultured rainbow trout.

Nowadays, antibiotics are widely used in aquatic animals to control and treatment of infections or as food supplement for growth increase and animal output. With increasing use of veterinary drugs in food production, there is global consideration about the consumption of antimicrobial residues in aquatic foods and their effects on human health. This study was aimed to evaluate the Oxytetracycline (OTC) residues in Rainbow trout meat in Shahre-kord (Iran) markets before and after frying. After randomized collection of 50 samples of fish in Shahre-kord markets in a six months period were examined. The prepared samples were examined for OTC residues using HPLC analytical method before and after frying. Results showed that 3 (6%) of the samples before frying and 12 (24%) after frying were having lower than Maximum residual limits (MRLs) in Codex alimentarius. However, mean OTC residues before and after frying samples were above MRLs. The mean amounts of OTC were 2260 +/- 1090 and 1110 +/- 930 ng g(-1) before and after frying, respectively. These findings show that the frying of fish reduces OTC residual. Nevertheless, the usage of OTC should be reduced to an acceptable level in fishery industry.

Significance of extracapillary proliferation in IgA-nephropathy patients with regard to clinical and histopathological variables.

BACKGROUND AND AIM: Extracapillary proliferation (crescent) was not included in the Oxford classification, although previous attempts to correlate the crescent with clinical outcomes have produced conflicting results. In this study, we investigated the clinical and morphological significance of extracapillary proliferation in a group of IgA nephropathy (IgAN) patients with regard to the Oxford classification. PATIENTS AND METHODS: In an observational study conducted on IgAN patients, we collected a total of 114 biopsies. We diagnosed IgAN by light and immunofluorescence for all patients. RESULTS: Of the 114 patients, 70.2% were male. The mean age of the patients was 37.7 ± 13.6 years. The mean proteinuria was 1742 ± 1324 mg/day. The mean serum creatinine was 1.6 ± 1.5 mg/dL. Twenty-five (21.9%) patient kidney biopsies had extracapillary proliferation. We found a significant positive correlation between the number of crescents and serum creatinine (p<0.001). Furthermore, we found a positive association between the nephrotic syndrome and the total number of crescents (p<0.05). Additionally, we observed a significant positive correlation between the amount of sclerosed glomeruli and extracapillary proliferation (p=0.028). CONCLUSION: Our findings confirm that extracapillary proliferation has a significant association with proteinuria and sclerotic glomeruli. We anticipate that extracapillary proliferation will be included in a revision of the Oxford classification of IgAN to widen the scope of the classification.

Natural cytotoxicity of NC-2+ cells against the growth and metastasis of WEHI-164 fibrosarcoma.

We have previously reported a new receptor (NC-2) for natural cytotoxicity (NC) on murine leucocytes, identified by monoclonal antibody D9 (mAb D9). Pretreatment of mouse spleen cells with different concentrations of mAb D9 in vitro blocked NC against WEHI-164, whereas natural killing (NK) activity against YAC-1 was unaffected. This paper reports the immune surveillance against the growth of WEHI-164 tumour cells in mice by NC-2(+) Cells. The kinetics of in vivo reduction in NC activity were investigated by treating BALB/c and (CBA × C57BL/6) F1 mice with a single injection of 40 µg of mAb D9 and monitoring splenic NC activity by (51) Cr-release assay at intervals from 24 h to 3 weeks. Control mice were injected with OKT8 irrelevant antibody. Results showed a significant (P < 0.05) reduction in splenic NC activity within 24 h which persisted for up to 1 week. Similar results were also obtained when (CBA × C57BL/6) F1 mice were employed (P<0.001). In vivo tumour studies were undertaken to investigate the role of NC-2(+) cells in surveillance against tumour growth and metastasis of the WEHI-164 fibrosarcoma. When syngeneic BALB/c mice were injected with 40 µg of mAb D9 and then challenged with 5 × 10(5) WEHI-164 cells, results showed significantly increased growth rate of the transplanted WEHI-164 fibrosarcoma and tumour nodules in the lungs of animals, when compared to control mice with normal NC activity. Our data support an innate surveillance in metastasis and growth of WEHI-164 fibrosarcoma in mice.

Contrasting actions of acute or chronic paroxetine and fluvoxamine on morphine withdrawal-induced place conditioning.

The acute and chronic effects of paroxetine and fluvoxamine on naloxone withdrawal-induced place aversion in morphine dependent rats were investigated. Acutely administered fluvoxamine (25 mg/kg s.c. given 30 min prior to naloxone withdrawal pairing) and chronic daily paroxetine (10 mg/kg s.c.) coadministration with a morphine induction protocol, both attenuated morphine withdrawal place aversion. Conversely, acutely administered paroxetine (up to 25 mg/kg s.c.) or chronic daily fluvoxamine (10 mg/kg s.c.) coadministration with morphine did not modify subsequent withdrawal place aversion. Previous radioligand binding studies indicate that fluvoxamine has opioid-displacing properties. It is suggested therefore that acute fluvoxamine may have decreased withdrawal aversion, probably through serotonin and also, in part, via an opioid-like mechanism whereas chronic paroxetine decreased withdrawal aversion by a serotonergic mechanism, but it is not clear whether opioid systems play any role in the action of paroxetine.