Determination of toxic metal burden and related risk factors in pregnant women: a biological monitoring in Sabzevar, Iran.

Nowadays, the adverse effect of toxic metals on humans is well known, especially in the fetal period such as preventing cognitive development and congenital abnormalities of the central nervous system. Hence, this study aims to evaluate the toxic metal burden in mothers and newborns in Sabzevar. Obtained data can be useful for authorities in public health issues. To determine heavy metals in placental blood and umbilical cord blood, one hundred eighty blood samples were taken from ninety mothers referred to Shahidan Mobini Hospital for delivery. The amount of metals in samples was analyzed using inductively coupled plasma optical emission spectrometry (ICP OES). The results of this study revealed that 21.52%, 26.19%, and 60.71% of maternal blood samples (placental blood) and 16.47%, 56.47%, and 20% of umbilical cord blood samples were higher than the US center for disease control (CDC) recommended levels for Pb, Cd, and As respectively. According to the multiple linear regression analysis, the Pb (p = 0.054), As (p < 0.001), and Se (p < 0.001) levels had an association with the mother's living area. Also, there was a significant association between Se (0.021) and the age of the mother. However, the Se values in its optimum concentrations in the blood (60-140 µg/L) can decrease the adverse effects of toxic metals, 72.5% of the pregnant women had Se values below the 60 µg/L and only 6% of pregnant women had Se levels higher than 140 µg/L. We concluded that the mothers inhabiting the rural areas need more Se sources in their diets.

The Role of 5-HT1A Receptors and Neuronal Nitric Oxide Synthase in a Seizur Induced Kindling Model in Rats.

BACKGROUND AND OBJECTIVE: Dentate gyrus (DG) has a high density of 5-HT1A receptors. It has neural nitric oxide synthase (nNOS), which is involved in neural excitability. The purpose of this study was to investigate the role of 5-HT1A receptors and nNOS of DG in perforant path kindling model of epilepsy. MATERIAL AND METHODS: To achieve this purpose, a receptor antagonist (WAY100635, 0.1 mg/kg, intracerebroventricular, i.c.v) and neuronal nitric oxide synthase inhibitor (7-NI, 15 mg/kg, intraperitoneal, i.p.) were injected during kindling aquisition. Adult male Wistar rats (280 ± 20 g) were used in this study Animals were kindled through the daily administration of brief electrical stimulations (10 stimulations per day) to the perforant pathway. Field potential recordings were performed for 20 min in DG beforehand. Additionally, glial fibrillary acidic protein (GFAP) expression rate in the DG was determined using immunohistochemistry as a highly specific marker for glia. RESULTS: WAY100635 (0.1 mg/kg) significantly attenuated the kindling threshold compared to the kindled + vehicle group (P < 0.001). The co-administration of WAY100635 with 7-NI, exerted a significant anticonvulsive effect. Furthermore, the slope of field Excitatory Post Synaptic Potentials (fEPSP) at the end of 10 days in the kindled + 7-NI + WAY100635 group was significantly lower than in the kindled + vehicle group (P < 0.001). Furthermore, immunohistochemistry showed that the density of GAFP+ cells in the kindled + 7-NI + WAY100635 group was significantly higher than in the kindled + vehicle group (P < 0.001). CONCLUSION: Our data demonstrate that antagonists of 5-HT1A receptors have proconvulsive effects and that astrocyte cells are involved in this process, while nNOS has an inhibitory effect on neuronal excitability.

The Effect of 6-gingerol on Growth Factors and Apoptosis Indices in Rats Exposed to Gold Nanoparticles.

INTRODUCTION: Research has shown that gold nanoparticles (AuNPs) can damage the physiological processes of brain tissue. Given the antioxidant properties of Gingerol (GING), this study aimed to determine the protective effect of 6-gingerol on hippocampal levels of Brain-Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), DNA oxidative damage, and the amount of Bax and Bcl2 apoptosis indices of rats exposed to AuNPs. METHODS: A total of 42 male Wistar rats were divided into four groups: control (30 days 0.5 mL saline), AuNPs (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL saline), AuNPs+GING 50 (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL density of gingerol 50 mg/kg), and AuNPs+GING100 (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL density of gingerol 100 mg/kg). At the end of the treatment period, the hippocampal levels of NGF, BDNF, 8-hydroxy-desoxyguanosine (8-HOdG), and apoptotic indices of Bax and Bcl-2 were assessed with the ELISA method. RESULTS: Compared with the AuNPs group, hippocampal levels of BDNF, NGF, and Bcl-2 in rats in the AuNPs+GING 50 and AuNPs+GING 100 groups significantly increased dose-dependently. However, the hippocampal levels of Bax and 8-HOdG significantly decreased dose-dependently (P<0.05). CONCLUSION: According to obtained results, gingerol may improve hippocampal BDNF and NGF levels in rats exposed to AuNPs, probably by reducing apoptosis and oxidative DNA damage.

Efficacy and tolerability of hydroalcoholic extract of Paeonia officinalis in children with intractable epilepsy: An open-label pilot study.

Despite a wide range of medications available to control epilepsy, seizures in more than 30 % of patients remain uncontrolled. However, in traditional medicine, Paeonia officinalis (P. officinalis), a native perennial herb of Southern Europe and Western Asia, has been used for an anticonvulsant effect for over 2000 years globally. In an open-label pilot study implemented on 30 children with intractable epilepsy aged 1-14 years, the hydroalcoholic extract of P. officinalis was administered. This study's purpose was to assess the efficacy and tolerability of the P. officinalis extract as an adjunct therapy to a patient's antiseizure medications in reducing the frequency and duration of the seizures in childhood intractable epilepsy. The mean frequency of seizures decreased significantly during treatment with the P. officinalis extract (P < 0.05). At the end of the intervention, 62.5 % and 36.7 % of the patients showed a≥50 % and a≥75 % reduction in seizure frequency, respectively. Regarding safety and tolerability, no serious adverse events occurred during the trial, although restlessness was reported in one child and the other children who experienced constipation, stopped treatment. The results show that the P. officinalis root extract was well tolerated and has contributed to a significant improvement in seizure control in children with medically intractable epilepsy. This trial was registered with the Iranian Registry of Clinical Trials (www.irct.ir; registration number: IRCT20131125015533N2.

The relationship between dietary intakes and prevalence of irritable bowel syndrome in adolescent girls: A cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder (FGID) leading to substantial reduction in quality of life. This study was undertaken to assess the relationship between diet and prevalence of IBS in female adolescents. METHODS: In this cross-sectional study, data were examined on 988 adolescent girls from different areas of Mashhad and Sabzevar cities, Iran. A 168-item validated and reliable food frequency questionnaire (FFQ) for dietary intake was used in all the study participants. A diagnosis of IBS was made using the Rome III criteria. RESULTS: Dietary macronutrients, energy, and selected micronutrients of IBS patients were similar to healthy subjects. Comparing the intake of caffeine between groups with and without IBS showed a higher level of consumption in the individuals with IBS (p-value = 0.02; p trend = 0.03). There was a significant positive association between caffeine intake and risk of IBS (odds ratio [OR] = 1.88, after adjustment for potential confounding variables). Although there was no significant difference in intakes of total dietary fiber (p-value = 0.23) and insoluble dietary fiber (p-value = 0.09) between IBS-positive and IBS-negative subjects, their soluble dietary fiber intake was significantly different (p-value = 0.02, a significant negative association was seen between soluble dietary fiber intake and IBS prevalence, after adjustment for potential confounding variables [p trend = 0.02; OR = 0.59]). CONCLUSIONS: The higher intake of caffeine was positively associated with IBS prevalence. Additionally, a negative association was seen between soluble dietary fiber intake and the chance of having IBS.

New anthropometric indices in the definition of metabolic syndrome in pediatrics.

Pediatrics metabolic syndrome (MetS) may be associated with the risk of development of chronic diseases in adulthood; however, the definition of pediatric MetS is unclear, and may vary with ethnicity. The primary goal of this study was to determine the best anthropometric predictors for pediatric MetS. For this purpose, 988 high school girls were recruited. Anthropometric indices and biochemical parameters were measured using standard procedures. The adapted MetS for pediatrics, including the IDF, NCEP, and two modified-NCEPs (Cook's and DeFerranti's) were used to establish a diagnosis of MetS. Statistical analysis was performed using SPSS and MedCalc softwares. Except for body frame size (r), the values for anthropometric indices were significantly lower in an individual without MetS. Waist to height (WHtR), BMI and hip circumference (HiC) showed the strongest association with the different MetS definitions. For the IDF definition, the highest sensitivity and specificity were observed for HiC (100.0, 85.2) and WHtR (100.0, 84.7); while for the NCEP definition, the r index showed the highest sensitivity (85.0); but low specificity made it inapplicable. For the Cook's definition of MetS, wrist circumference (WrC), HiC, WHtR, BMI and SR had similar sensitivity values with WC (92.9%), and HiC (85.3%) have the highest specificity. WHtR (86.05, 80.5), SR (86.05, 82.7) and HiC (76.7, 87.0) sensitivity and specificity were the best indexes for DeFerranti's criteria. Based on this date, we concluded that HiC and WHtR might be helpful as auxiliary indexes for pediatric MetS definition; however, further studies are required in both genders.

The effect of harmaline on seizures induced by amygdala kindling in rats.

OBJECTIVE: Harmaline and other beta-carbolines act as an inverse agonist for GABA-A receptors and cause central nervous system stimulation and anxiety; thus, it may act hypothetically as a potential seizure augmenter. To examine the hypothesis, the effect of harmaline during the seizures induced by amygdala kindling is investigated here. METHODS: Seven groups of male rats were kindled by daily electrical stimulation of the amygdala. After being kindled, Groups I-III, respectively, received 5, 15 and 50 mg/kg harmaline through intraperitoneal injection. The rats in Groups IV and V received vehicle daily (1 ml/kg) and harmaline (5 mg/kg) daily through intraperitoneal injection. Groups VI and VII received artificial cerebrospinal fluid and harmaline (50 mM) through intraventricular injection, respectively. RESULTS: In addition to significant increase of some seizure parameters in the fully kindled groups, harmaline significantly increased cumulative afterdischarge duration (P < 0.05) and decreased stage 1 latency (P < 0.01) in the acquisition groups (Groups V and VII). In Group VII, seizure duration showed a significant increase (P < 0.01) while stage 1 latency and stage 4 latency decreased significantly (P < 0.01). DISCUSSION: According to the results, it is suggested that harmaline may increase neuronal activity and the production of high-frequency action potentials by stimulating NMDA receptors and inhibiting GABA receptors. Overall, drugs and plants containing harmaline may be harmful to epileptic-susceptible people during some traditionally and costume treatments, so these should be avoided.

The role of serotonin and its receptors on the anticonvulsant effect of curcumin in pentylenetetrazol-induced seizures.

AIM: Curcumin, derived from turmeric, has been demonstrated to be effective in controlling seizures, although the exact mechanism is yet unknown. In this study, the role of serotonin and its receptors in the anticonvulsant effect of curcumin was evaluated in mice. MAIN METHODS: Total 110 mice were randomly divided into 11 groups (n = 10). In the first to the fourth groups, the role of curcumin (150 mg/kg, i.p) and serotonin (PCPA (100 mg/kg); was used to deplete the brain serotonin levels) was investigated. The fifth group first received NAD-299 (4 mg/kg, sc), RS-102221 (5 mg/kg, i.p), SDZ205-557 Hydrochloride (1 mg/kg, i.p), and SB 26997 (10 mg/kg, i.p), then curcumin. The sixth group received NAD-299, curcumin. The animals in the seventh to ninth groups received 5-HT2C, 5-HT4, and 5-HT7 antagonists, respectively, with curcumin. The tenth group received HTR2C antagonist and the eleventh group received HTR4 antagonist. In all animals 25 min after curcumin PTZ (80 mg/kg; i.p) was injected. KEY FINDINGS: PCPA not only inhibited the anticonvulsant action of curcumin, but also reversed some of its anticonvulsant effect. The 5-HT1A, 5-HT2C and 5-HT4 antagonists diminished but 5-HT7 antagonist strengthened the anticonvulsant effect of curcumin. Evaluation of gene expression using real-time PCR confirmed that only 5-HT7 gene expression was reduced after curcumin injection. SIGNIFICANCE: According to these results, it may be suggested that curcumin exerts anticonvulsive effects by increasing the serotonin levels in the brain that influence receptors, including 5-HT1A, 5-HT2C, and 5-HT4 and likely through the reduction of 5-HT7 gene expression.

Do sufficient vitamin D levels at the end of summer in children and adolescents provide an assurance of vitamin D sufficiency at the end of winter? A cohort study.

BACKGROUND: The changes in serum 25-hydroxyvitamin D (25(OH)D) in adolescents from summer to winter and optimal serum vitamin D levels in the summer to ensure adequate vitamin D levels at the end of winter are currently unknown. This study was conducted to address this knowledge gap. METHODS: The study was conducted as a cohort study. Sixty-eight participants aged 7-18 years and who had sufficient vitamin D levels at the end of the summer in 2011 were selected using stratified random sampling. Subsequently, the participants' vitamin D levels were measured at the end of the winter in 2012. A receiver operating characteristic (ROC) curve was used to determine optimal cutoff points for vitamin D at the end of the summer to predict sufficient vitamin D levels at the end of the winter. RESULTS: The results indicated that 89.7% of all the participants had a decrease in vitamin D levels from summer to winter: 14.7% of them were vitamin D-deficient, 36.8% had insufficient vitamin D concentrations and only 48.5% where able to maintain sufficient vitamin D. The optimal cutoff point to provide assurance of sufficient serum vitamin D at the end of the winter was 40 ng/mL at the end of the summer. Sex, age and vitamin D levels at the end of the summer were significant predictors of non-sufficient vitamin D at the end of the winter. CONCLUSIONS: In this age group, a dramatic reduction in vitamin D was observed over the follow-up period. Sufficient vitamin D at the end of the summer did not guarantee vitamin D sufficiency at the end of the winter. We found 40 ng/mL as an optimal cutoff point.

Effect of conjugated linoleic acid supplementation on quality of life in rectal cancer patients undergoing preoperative Chemoradiotherapy.

OBJECTIVES: This study set out with the aim of evaluating the effect of conjugated linoleic acid (CLA) supplementation on quality of life in rectal cancer patients undergoing to preoperative chemoradiotherapy. METHODS: In this study, 33 volunteer patients with rectal cancer treated with preoperative chemoradiotherapy were allocated in the CLA (n=16) and the placebo groups (n=17). The CLA group and placebo groups received 3 gr CLA/d and 4 placebo capsules for 6 weeks respectively. Before and after intervention, quality of life of patients was assessed by EORTC QLQ-C30. RESULTS: At the end of study, the mean scores of physical function, role function, and cognitive function enhanced significantly in the CLA group while reduced remarkably in the placebo group. Symptom scales improved in the CLA group at the end of study. Comparison of changes in fatigue, pain and diarrhea scores were statistically significant between two study groups (P<0.05). When we compared the global health status scores between two groups, significant changes were observed (P<0.001). CONCLUSION: It appears that CLA may be helpful in rectal cancer patients by improving global quality of life. Although, other clinical trials with large sample size are needed to achieve more precise results.

The antiepileptogenic effect of low-frequency stimulation on perforant path kindling involves changes in regulators of G-protein signaling in rat.

G-protein coupled receptors may have a role in mediating the antiepileptogenic effect of low-frequency stimulation (LFS) on kindling acquisition. This effect is accompanied by changes at the intracellular level of cAMP. In the present study, the effect of rolipram as a phosphodiesterase inhibitor on the antiepileptogenic effect of LFS was investigated. Meanwhile, the expression of αs- and αi-subunit of G proteins and regulators of G-protein signaling (RGS) proteins following LFS application was measured. Male Wistar rats were kindled by perforant path stimulation in a semi-rapid kindling manner (12 stimulations per day) during a period of 6days. Application of LFS (0.1ms pulse duration at 1Hz, 200 pulses, 50-150µA, 5min after termination of daily kindling stimulations) to the perforant path retarded the kindling development and prevented the kindling-induced potentiation and kindling-induced changes in paired pulse indices in the dentate gyrus. Intra-cerebroventricular microinjection of rolipram (0.25µM) partially prevented these LFS effects. Twenty-four hours after the last kindling stimulation, the dentate gyrus was removed and changes in protein expression were measured by Western blotting. There was no significant difference in the expression of α-subunit of Gs and Gi/o proteins in different experimental groups. However, application of LFS during the kindling procedure decreased the expression RGS4 and RGS10 proteins (that reduce the activity of Gi/o) and prevented the kindling-induced decrease of RGS2 protein (which reduces the Gs activity). Therefore, it can be postulated that the Gi/o protein signaling pathways may be involved in antiepileptogenetic effect of LFS, and this is why decreasing the cAMP metabolism by rolipram attenuates this effect of LFS.

Tactile learning in rodents: Neurobiology and neuropharmacology.

Animal models of learning and memory have been the subject of considerable research. Rodents such as mice and rats are nocturnal animals with poor vision, and their survival depends on their sense of touch. Recent reports have shown that whisker somatosensation is the main channel through which rodents collect and process environmental information. This review describes tactile learning in rodents from a neurobiological and neuropharmacological perspective, and how this is involved in memory-related processes.

Inhibition of amyloid fibril formation and cytotoxicity by a chemical analog of Curcumin as a stable inhibitor.

Clinical application of curcumin for Alzheimer's disease treatment is severely limited with regard to its poor bioavailability, high rate of metabolism, and instability under neutral condition. In the current study, we designed three compounds in which the diketone moiety of curcumin was replaced by cyclohexanone. In these compounds, the linker length of the molecules was optimal; and substitution of dioxolane for hydroxyl groups on compound 3 should prevent metabolic inactivation. The inhibitory effect of the compounds was investigated against hen egg white lysozyme (HEWL) fibrillation using AFM (atomic force microscope), ThT (thioflavin T) and MTT assay. We found that all three compounds were able to inhibit HEWL aggregation in a dose-dependent manner and inhibit the cytotoxic activity of aggregated HEWL. Docking results demonstrated that the compounds could bind into lysozyme and occupy the whole active site groove. In conclusion, we present chemical analogs of curcumin with various modifications in the spacer and the phenolic rings as improved inhibitors of amyloid aggregation.

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll-like receptor 4 expression in neuropathic rats.

It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper-responsiveness of wide dynamic range neurons (WDR) and Toll-like receptor 4 (TLR4) expressions in a chronic constriction injury (CCI) model of neuropathic pain in rats. Adult male Wistar rats (230 ± 30 g) underwent surgery for induction of CCI neuropathy. Six days after surgery, administration of minocycline (10, 20, and 40 mg/kg, i.p.) was initiated and continued until day 14. After administration of the last dose of minocycline or saline, a behavioral test was conducted, then animals were sacrificed and lumbar segments of the spinal cord were collected for Western blot analysis of TLR4 expression. The electrophysiological properties of WDR neurons were investigated by single unit recordings in separate groups. The findings showed that after CCI, in parallel with thermal hyperalgesia, the expression of TLR4 in the spinal cord and the evoked response of the WDR neurons to electrical, mechanical, and thermal stimulation significantly increased. Post-injury administration of minocycline effectively decreased thermal hyperalgesia, TLR4 expression, and hyper-responsiveness of WDR neurons in CCI rats. The results of this study indicate that post-injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyper-responsiveness. This study confirms that post-injury modulation of microglial activity is a new strategy for treating neuropathic pain.

High-Level Soluble Expression and One-step Purification of HTLV-I P19 Protein in Escherichia coli by Fusion Expression.

Expression of HTLV-I p19 protein in an Escherichia coli expression system always leads to the formation of inclusion body. Solubilisation and refolding of the inclusion bodies is complex, time consuming and difficult during large-scale preparation. This study aimed to express and purify a soluble form of recombinant HTLV-I p19 protein in an E. coli expression system. The synthetic DNA encoding the p19 was subcloned into a pGS21a vector along with a His-GST solubility/purification tag. The recombinant pGS21a-p19 vector was then transformed into chemically competent E. coli BL21 (DE3) cells, and expression of the recombinant His-GST-p19 protein was induced by IPTG. Expression and distribution of the His-GST-p19 protein in soluble and insoluble fractions were evaluated using SDS-PAGE. Antigenicity of the His-GST-p19 protein was evaluated using ELISA after purifying the protein using Ni-NTA affinity chromatography, then compared to the results of synthetic immunodominant p19 peptide ELISA. The fusion His-GST-p19 protein accounted for 30% of the total cellular proteins. The SDS-PAGE results indicated that approximately 50% of the expressed His-GST-p19 proteins were soluble and accounted for 50% of the total soluble proteins. ELISA showed that the His-GST tag did not impair the antigenicity of the p19 protein and that the fusion protein reacted with HTLV-I antibodies in a concentration-dependent manner. The results of His-GST-p19 ELISA indicated that specificity of p19 reactivity was compatible to the results of p19 peptide ELISA. Combination of key strategies for the soluble expresion of proteins, like fusion with solubility/purification tags, low IPTG concentration and induction at low temperature, provide an efficient and facile platform for producing soluble  HTLV-I p19 protein.

Termination of Nociceptive Bahaviour at the End of Phase 2 of Formalin Test is Attributable to Endogenous Inhibitory Mechanisms, but not by Opioid Receptors Activation.

INTRODUCTION: Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet. Phase II is a consequence of peripheral and central sensitization processes, which can lead to termination of the noxious stimuli responses; 45-60 minutes after formalin injection via possible recruitment of active inhibitory mechanisms which we have investigated in this study. METHODS: To test our hypothesis, in the first set of experiments, we evaluated nociceptive response after two consecutive injection of formalin (50µL, 2%), with intervals of 5 or 60 minutes. In the next set, formalin tests were carried out in companion with injection of Naloxone Hydrochloride, a non-selective antagonist of opioid receptors, pre-formalin injection and 30 and 45 minutes post formalin injection. RESULTS: While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection. While second injection of formalin, 5 minute after first injection, had no effect. Administration of naloxone (1mg/kg) decreased nociception in phase 2A; but had no effect on delayed termination of formalin test. DISCUSSION: The results of this study suggest the existence of an active inhibitory mechanism, other than the endogenous opioids, that is responsible for termination of nociceptive behaviour at the end of formalin test.

Permanent lesion in rostral ventromedial medulla potentiates swim stress-induced analgesia in formalin test.

OBJECTIVE(S): There are many reports about the role of rostral ventromedial medulla (RVM) in modulating stress-induced analgesia (SIA). In the previous study we demonstrated that temporal inactivation of RVM by lidocaine potentiated stress-induced analgesia. In this study, we investigated the effect of permanent lesion of the RVM on SIA by using formalin test as a model of acute inflammatory pain. MATERIALS AND METHODS: Three sets of experiments were conducted: (1) Application of stress protocol (2) Formalin injection after exposing the animals to the swim stress (3) Either the relevant vehicle or dopamine receptor 1 (D1) agonist R-SKF38393 was injected into the RVM to cause a lesion. For permanent lesion of RVM, R-SKF38393 was injected into the RVM. Forced swim stress in water was employed in adult male rats. Nociceptive responses were measured by formalin test (50µl injection of formalin 2% subcutaneously into hind paw) and pain related behaviors were monitored for 90 min. RESULTS: In the unstressed rats, permanent lesion of the RVM by R-SKF38393 decreased formalin-induced nociceptive behaviors in phase 1, while in stressed rats, injection of R-SKF38393 into the RVM potentiated swim stress-induced antinociception in phase 1 and interphase, phase 2A of formalin test. Furthermore, R-SKF38393 had pronociceptive effects in phase2B whereas injections of R-SKF38393 resulted in significant difference in nociceptive bahaviours in all phases of formalin test (P<0.05). CONCLUSION: The result of the present study demonstrated that permanent inactivation of RVM can potentiate stress-induced analgesia in formalin test.

Modulation of Different Phases of Formalin Test by Force Swim Stress.

INTRODUCTION: The formalin test is the most accepted chemical test for evaluation of nociception. It requires the injection of an adequate amount of formalin into the surface of the hindpaw. Formalin test consists of phase 1 (0-7 min) and phase 2 (15-60) in which the animal shows painful behaviors. These phases are separated with a quiet phase named interphase, in which the nociceptive responses are decreased or completely disappeared. METHODS: The goal of the current study was to evaluate the effects of swim stress at different heights of water on different phases of the formalin test in male rats. RESULTS: Swim stress decreased nociceptive behaviors in first phase and prolonged interphase or delayed the start of second phase in a water height dependent manner. Swim stress in 25 and 50cm completely abolished the nociceptive behaviors in phase 1. DISCUSSION: The present results showed different pain modulation during different phases of the formalin test and elucidated the impact of swim stress on duration of interphase. Interphase considered as an inactive period, but a recent research has shown that active inhibitory mechanisms are involved in the modulation of pain during this period. Therefore, swim stress may be considered as a useful tool for study of the basic inhibitory mechanisms underlying attenuation of nociceptive behaviors between phase 1 and 2 of the formalin test.

Validation of nutritional risk index method against patient-generated subjective global assessment in screening malnutrition in colorectal cancer patients.

OBJECTIVE: To validate malnutrition screening tool of nutrition risk index (NRI) against patient-generated subjective global assessment (PG-SGA) as a gold standard tool in colorectal cancer patients before radiotherapy. METHODS: Nutritional status of 52 volunteer colorectal cancer patients with a mean age of 54.1±16.8 years who referred to radiotherapy center were assessed by PG-SGA (gold standard method) and NRI. Serum albumin levels of patients were determined by colorimetric method. A contingency table was used to determine the sensitivity, specificity, and predictive value of the NRI in screening patients at risk of malnutrition, in comparison with the PG-SGA in patients before radiotherapy. RESULTS: The findings of PG-SGA and NRI showed that 52% and 45% of patients in our study were moderately or severely malnourished respectively. The NRI had a sensitivity of 66% and a specificity of 60% against PG-SGA. The positive predictive value was 64% and the negative predicative value was 62%. The agreement between NRI and PG-SGA was statistically insignificant (kappa =0.267; P>0.05). CONCLUSIONS: The findings of present study showed that the prevalence of malnutrition was high in patients with colorectal cancer. Moreover, NRI method had low sensitivity and specificity in assessing nutritional status of patients with cancer. It seems that the combination of anthropometric, laboratory parameters and a subjective scoring system may be helpful tools in screening of malnutrition in cancer patients.

The effect of minocycline on seizures induced by amygdala kindling in rats.

PURPOSE: Minocycline is known as a chemical with neuroprotective, anti-inflammatory, and antimicrobial properties. In this study, the effects of minocycline on seizures induced by amygdala kindling in rats were studied. METHODS: Kindled Wistar rats were injected intraperitoneally with saline and, on the following day, with minocycline (50, 25, and 12.5mg/kg for the three groups (1-3), respectively). The animals in groups 1-3 had similar protocols. Groups 4 and 5 were given for the rotarod test and received 25 or 50mg/kg minocycline, respectively, without any kindling stimulation. The animals in groups 6 and 7 (seven each) received 25mg/kg minocycline or saline, respectively. All the injections were carried out 1h before kindling stimulation. Seizure parameters, including after discharge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and seizure duration (SD), were recorded and compared with those of the saline groups. RESULTS: Minocycline (50mg/kg) significantly reduced ADD, 1/S4L, S5D, and SD (P<0.001, P<0.05, P<0.001, and P<0.001, respectively) in group 1. While the administration of 25mg/kg of minocycline decreased the ADD and S5D (P<0.05), in group 2. The injection of 12.5mg/kg resulted in decreased S5D (P<0.001) in group 3. The daily injection of minocycline (25mg/kg) significantly decreased ADD, S5D, and SD (P<0.001) in group 6. CONCLUSION: The obtained results revealed that minocycline has anticonvulsant effect on seizures induced by amygdala kindling. Thus, it may be useful for epilepsy treatment.