Comorbidity of asthma in patients with attention-deficit/hyperactivity disorder (ADHD) aged 4-12 years in Iran: a cross-sectional study.

Attention-deficit/hyperactivity disorder (ADHD) is defined as a stable pattern of attention deficits or impulsive hyperactivity that can interfere with the functioning, growth, and development of individuals. It is believed that both the type of asthma and the medications used to treat it exacerbate the symptoms of ADHD. Methods and Materials: The present study was a cross-sectional analytical study conducted to investigate the incidence of asthma in ADHD patients aged 4-12 years who were referred to Urmia University of Medical Sciences clinics and hospitals. In this study, ADHD patients were diagnosed through a psychiatric interview and based on a paediatric asthma questionnaire (approved by asthma and allergy organizations and scientific institutions), and individuals with suspected asthma were selected. All 101 ADHD patients referred to these clinics during the specified period were examined. Five patients were excluded from the study because of lack of cooperation or incomplete information. Then, the selected subjects were divided into two age groups of less than 5 years and between 5 and 12 years. The final diagnosis of asthma was made by clinical findings and demographic questionnaire in subjects younger than 5 years, while it was made by spirometry in subjects between 5 and 12 years. Data analysis was conducted using SPSS software. Results: The mean age of the 96 samples included in the study was 7.67 years with a standard deviation of 7.214. Sixteen of them (16.7%) were under 5 years of age and eighty of them (83.3%) were between 5 and 12 years of age. Asthma was diagnosed in 7 children under 5 years of age (7.3%) and in 14 children (14.6%) between 5 and 12 years of age. A total of 21 (21.9%) were diagnosed as having asthma after screening. On the basis of these results, the frequency of asthma according to classified age was significant (P=0.020). The frequency of asthma based on sex and birth rank was also examined, and none of these factors showed a significant association with asthma. Medications taken by the ADHD patients were also examined in this study. The most commonly used medications in both groups of patients with asthma and no asthmatic patients were a combination of risperidone and atomoxetine or risperidone alone. The prevalence of asthma in the target population was also assessed in terms of parental smoking. Conclusions: According to the results of this study, the incidence of asthma in ADHD patients aged 4-12 years is high, and this case is more frequent in subjects younger than 5 years than in subjects aged 5-12 years. It should be noted that according to the results of the present study, there was no significant association between birth rank, parental smoking, ADHD medication, and the frequency of asthma.

Anesthesia and analgesia for common research models of adult mice.

Anesthesia and analgesia are major components of many interventional studies on laboratory animals. However, various studies have shown improper reporting or use of anesthetics/analgesics in research proposals and published articles. In many cases, it seems "anesthesia" and "analgesia" are used interchangeably, while they are referring to two different concepts. Not only this is an unethical practice, but also it may be one of the reasons for the proven suboptimal quality of many animal researches. This is a widespread problem among investigations on various species of animals. However, it could be imagined that it may be more prevalent for the most common species of laboratory animals, such as the laboratory mice. In this review, proper anesthetic/analgesic methods for routine procedures on laboratory mice are discussed. We considered the available literature and critically reviewed their anesthetic/analgesic methods. Detailed dosing and pharmacological information for the relevant drugs are provided and some of the drugs' side effects are discussed. This paper provides the necessary data for an informed choice of anesthetic/analgesic methods in some routine procedures on laboratory mice.

Efficacy of viable BCG vaccine paste in the treatment of common warts: a double-blind randomized control trial.

BACKGROUND: Treatment of common warts may be painful or leaves scars, mainly using traditional destructive methods. This study aimed to evaluate the efficacy of the viable Bacillus Calmette-Guérin (BCG) vaccine in paste formula as an immunotherapeutic modality for common warts treatment. METHODS: This double-blind and randomized, parallel-group, placebo-controlled trial was conducted at the Ahvaz Imam Hospital Dermatology Department from November 2014 to 2015. Overall 80 patients with common warts in two groups (case and control) received BCG vaccine paste once weekly for eight consecutive weeks. Follow-up was done every two weeks during treatment and six months after the treatment to evaluate recurrence in patients with complete resolution. RESULTS: In group A, eight patients (20%) had a complete response, 15 patients (37.5%) partial response, four patients (10%) low response, and 13 patients (32.5%) no response (p < .001). All patients in group B had no response to treatment (p < .001). After six months of follow-up, no recurrence was seen. Duration of disease less than 12 months (p = .001) and the number of lesions less than three (p = .01) were determining factors of response to treatment. CONCLUSION: Topical BCG vaccine paste was an effective treatment for common warts, without recurrence and significant complications.

Pepsin Hydrolysis of Orange By-Products for the Production of Bioactive Peptides with Gastrointestinal Resistant Properties.

Recently, the use of bioactive compounds in improving human health has received more attention. The aim of the present study was to hydrolyze orange seed proteins using pepsin enzyme to obtain bioactive peptides as well as to study the stability of such activity after simulated gastrointestinal digestion conditions. The method was optimized using different enzyme concentrations from 1% to 3%, hydrolysis times between 2 and 5 h, and an optimal temperature of 33 °C. Biological activities including α-glucosidase inhibition, α-amylase inhibition, Angiotensin I-Converting Enzyme (ACEI) inhibition, ferric reducing antioxidant power, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity were evaluated. According to the results, a significant higher value of the biological activity (p < 0.05) was observed using an enzyme ratio of 0.03 E/S and hydrolysis time of 3.5 h. After size-exclusion chromatography separation, fractions 45-49 and 50-54 showed the highest biological roles such as antioxidant, ACEI inhibitory, and hypoglycemic. Fractions with the highest biological activity were purified using RP-HPLC and analyzed using nano-liquid chromatography and mass spectrometry. The results obtained after simulated gastrointestinal digestion indicated that peptide fractions obtained after chromatographic separation significantly maintain their activity.

Simvastatin prevents morphine antinociceptive tolerance and withdrawal symptoms through antioxidative effect and nitric oxide pathway in mice.

Oxidative stress and the nitric oxide (NO) pathway are involved in the development of opioid analgesic tolerance and dependence. Simvastatin modulates NO and oxidative stress, so the present study aimed to investigate its effect on the development and expression of morphine analgesic tolerance and withdrawal signs in mice. Morphine tolerance and dependence were induced by twice daily morphine injection (10 mg/kg, s.c.) for 5 consecutive days. Tolerance was assessed by the hot-plate test and dependence by naloxone challenge, on the sixth day. To determine if the NO is involved in the effects of simvastatin, mice were pre-treated with l-arginine (200 mg/kg) or the NO synthesis inhibitors (L-NAME; 30 mg/kg) along with simvastatin (300 mg/kg). The results showed that acute and chronic administration of simvastatin reversed the antinociceptive tolerance of morphine and attenuated withdrawal signs in morphine-dependent mice, and this effect is reversed by l-arginine and augmented by l-NAME. Also, the concentration of NO and oxidative stress factors such as malondialdehyde content, total thiol, and glutathione peroxidase (GPx) activity in brain tissues was evaluated. Chronic administration of simvastatin reduced NO and malondialdehyde, and increased total thiol and GPx levels in the cerebral cortex and hippocampus of morphine-dependent mice which were antagonized by l-arginine, and augmented by l-NAME. In summary, simvastatin attenuates morphine-induced antinociceptive tolerance and withdrawal symptoms, at least partly, through antioxidative properties and nitric oxide pathway.

Ten-year-old boy with atypical COVID-19 symptom presentation: A case report.

Since reactive arthritis (ReA) and urticaria could be seen in this age group along with atypical COVID-19 symptom presentation, pediatrics should be familiar with urticarial rashes and ReA in COVID-19 to enable early diagnoses of infected individuals.

Gallic acid ameliorates sodium arsenite-induced renal and hepatic toxicity in rats.

Chronic exposure to toxic inorganic arsenic results in the adverse health effects including skin lesions, cardiovascular diseases, diabetes, neurological disorders, and liver and kidney diseases. Gallic acid (GA) is an important phenolic compound, which could protect different tissues from oxidative stress induced damage. The present study investigated effects of GA against sodium arsenite (SA)-induced renal and hepatic toxicity. Thirty-five rats were randomly divided in to five groups; group 1 was treated with normal saline (2 ml/kg/day, p.o.; for 21 days); group 2 was exposed to SA (10 mg/kg/day, p.o.; for 14 days); groups 3 and 4 were treated with GA (10 and 30 mg/kg/day, respectively; for 7 days) prior to exposure to SA, and treatment was continued up to 21 days in parallel with SA administration; group 5 was treated with GA (30 mg/kg/day, p.o.; for 21 days). The level of MDA, IL-1ß, NO and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were evaluated in kidney and liver tissues. Histopathological parameters and serum levels of ALT, AST, ALP, Cr and BUN were also assessed. Treatment with GA remarkably improved SA-induced alteration of hematological and histopathological parameters; these protective effects were associated with the reduction of SA-induced elevation of MDA, IL-1ß and NO levels as well as reduction of GSH level and GPx, SOD and CAT activity. Our results suggest that GA may inhibit SA-induced kidney and liver toxicity through scavenging reactive free radicals and increasing intracellular antioxidant capacity.

Impact of Simulated Gastrointestinal Digestion on the Biological Activity of an Alcalase Hydrolysate of Orange Seed (Siavaraze, Citrus sinensis) by-Products.

In this study, orange seed proteins were hydrolyzed by Alcalase enzyme at different enzyme concentrations 1-3% (v/w) and hydrolysis times (2-5 h), to obtain bioactive peptides showing antioxidant, Angiotensin-converting enzyme (ACE) -inhibitory, and hypoglycemic activities. The highest biological activities (p < 0.05) were achieved by using a hydrolysis time of 5 h and an enzyme concentration of 2%. Orange seed protein hydrolysate (OSPH) was prepared under these conditions, and peptides were isolated and purified by using size-exclusion chromatography and high-performance liquid chromatography, respectively. The fractions that showed the highest biological activities were analyzed by mass spectrometry in tandem, and a total of 63 peptide sequences were found. Moreover, the effect of simulated gastrointestinal digestion on the bioactivity of the fractions was studied, and the novel peptide sequences generated were also identified. Overall, despite there being some differences in the profile of peptide sequences obtained, the main results showed non-significant differences in the analyzed bioactivities after simulated gastrointestinal digestion.

The effect of oxytocin vaginal gel on vaginal atrophy in postmenopausal women: a randomized controlled trial.

BACKGROUND: Around 90% of postmenopausal women are suffering from vaginal atrophy. This study aimed to evaluate the effect of oxytocin vaginal gel on vaginal atrophy among postmenopausal women. METHODS: This was a randomized controlled trial that was conducted on 96 postmenopausal women who suffered from vaginal atrophy. The inclusion criteria were: literate women, age 40-60, at least 1 year passed from their last menstrual period or the level of FSH > 40 IU, monogamous women with the sexual relationship. Women in the intervention group, requested to use one applicator of 400 IU oxytocin gel per night and women in the placebo group used placebo each night. The subjective symptoms of vaginal atrophy, vaginal PH, maturation index were measured before and after the intervention. RESULTS: The number of superficial cells was increased significantly in the oxytocin group compared to placebo (38.7 ± 7.18 vs. 3.69 ± 2.76, p = 0.0001), while the number of parabasal cells was decreased significantly in the oxytocin compared to placebo after the intervention. The improvement of the maturation index was more dominant in the oxytocin group (increased from 7.76 ± 4.68 to 52.48 ± 7.54) in comparison to the placebo group (increased from 8.58 ± 4.35 to 13.25 ± 5.06). The PH of the vagina decreased significantly in the oxytocin group in comparison to the placebo group (p = 0.0001). After 8 weeks, 88.6 and 7.1% of women in the oxytocin and placebo groups did not show the severe symptoms of vaginal atrophy (p = 0.001). CONCLUSION: The results of this study showed that eight- week intervention with oxytocin vaginal gel (400 IU) could significantly improve the vaginal maturation index, subjective symptoms of vaginal atrophy and reduce the PH of the vagina. Using this medication in women who have a contraindication for hormone therapy is recommended. TRIAL REGISTRATION: IRCT20160602028220N2.

The Effect of Orexin Receptor Antagonism on Quinpirole-Induced Compulsive-Like Checking Behavior in Rats.

The orexinergic system supposedly plays a role in stress circuits for arousing behaviors during anxiety, suggesting that it may play a role also in neural circuits mediating the compulsive behavior characteristic of obsessive-compulsive disorder (OCD). This study aims to investigate the roles of the orexinergic system in the development of OCD behaviors, using as preparation the induction of compulsive checking by chronic treatment with the D2/D3 agonist, quinpirole. Repeated injections of quinpirole (0.5 mg/kg, twice per week for a total of 10 injections) were used to induce compulsive checking. In separate groups of rats, OX1R (SB334867-A; 10 µg i.c.v) and OX2R (TCS-OX2-29; 10 µg i.c.v) receptor antagonists were co-administered together with quinpirole. Checking behavior in a large open field was measured after the first, fifth, and tenth injections of the drugs. SB334867-A attenuated checking behavior and the level of anxiety. TCS-OX2-29 administration ameliorated anxiety but did not block the development of compulsive checking. Orexin 1 receptors seem to play a more critical role than orexin 2 receptors in the induction of compulsive checking. Considering that the quinpirole sensitization model of OCD involves activation of dopamine systems and sensitization to quinpirole, it is suggested that neural interaction between orexigenic and dopamine systems may be important in the pathogenesis of OCD.

The Impact of Oxytocin Vaginal Gel on Sexual Function in Postmenopausal Women: A Randomized Controlled Trial.

Many postmenopausal women suffer from sexual dysfunction mostly due to the vulvovaginal atrophy. The aim of this study was to assess the effect of vaginal oxytocin gel on sexual function of postmenopausal women. This study was conducted on 96 postmenopausal women with symptoms of vaginal atrophy and sexual dysfunction who were randomly recruited into two groups of oxytocin vaginal gel (400 IU, n = 48) or placebo (n = 48). The PH, vaginal maturation index, and sexual function (using Female Sexual Function Index) of the participants were measured at the beginning of the study and eight weeks later. The vaginal maturation index and the PH of the vagina improved in the oxytocin group compared to those of the placebo. All domains of sexual function including desire, arousal, lubrication, pain, sexual satisfaction, and total score of sexual function improved significantly in the oxytocin gel compared to the control group (p < 0.0001). The results of this study showed that the administration of oxytocin vaginal gel could significantly improve vaginal atrophy as well as sexual function in postmenopausal women. Therefore, using vaginal oxytocin gel for sexual dysfunction in postmenopausal women who are not interested in hormone therapy is recommended.

Effect of Sodium Cromoglycate on Acetic Acid-induced Ulcerative Colitis in Mice.

Background/Aims: Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment. Methods: To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations. Results: In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67±0.18 and 1.73±0.21 (p<0.05), respectively, compared to the UC control group (3.21±0.31), and were higher than that of the group given the standard treatment of 100 mg/kg SSZ (1.10±0.09). The treatment groups with 50 and 100 mg/kg of SCG showed a lower clinical gross lesion score than the UC control group (2.91±0.28 and 2.10±0.43, vs. 4.49±0.61, p<0.05) and were higher than the standard group (0.95±0.18). Treatment with SCG (100 mg/kg) decreased the macroscopic scores significantly compared to the UC control group (p<0.05) on the 8th day. Conclusions: SCG (100mg/kg) decreased significantly the clinical activity score, gross lesion, and percentage-affected area compared to the UC controls on the 8th day.

Celecoxib inhibits acute edema and inflammatory biomarkers through peroxisome proliferator-activated receptor-γ in rats.

OBJECTIVES: Celecoxib (CLX), a selective cyclooxygenase-II (COX-2) inhibitor, has been used for management of several inflammatory disorders. The present study aimed to explore the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in CLX induced anti-inflammatory response in rats. MATERIALS AND METHODS: Carrageenan-induced paw edema was used as an acute inflammation model. Rats were treated with various intra-peritoneal (IP) doses of CLX (0.3-30 mg/kg) and pioglitazone (PGL; PPARγ agonist, 1-20 mg/kg) alone or in combination. Amounts of PPARγ, COX-2, and prostaglandin E2 (PGE2) in paw tissue, and extents of TNF-α and IL-10 in serum were measured. Moreover, levels of oxidative stress parameters as malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) activity in the cortex, hippocampus, and paw tissues were also determined. RESULTS: CLX and PGL dose-dependent administration (IP), alone or in combination reduced carrageenan-induced paw edema. Further, both agents, alone or in combination, reduced either the amounts of COX-2, PGE2, and MDA in the inflamed paw, and the levels of TNF-α in serum which were elevated by carrageenan. Both drugs also increased both levels of PPARγ, GSH, GPx activity in paws, and serum levels of IL-10 that were decreased by carrageenan. Intraplantar injection of GW-9662 (IPL), a selective PPARγ antagonist, inhibited all biochemical modifications caused by both single and combined drug treatments. CONCLUSION: CLX produced its anti-inflammatory effects probably through PPARγ receptor activation. Besides, increased anti-inflammatory effects of CLX with PGL suggest that their combination might be applied for the clinical management of inflammation especially in patients suffering from diabetes.

Venlafaxine inhibits naloxone-precipitated morphine withdrawal symptoms: Role of inflammatory cytokines and nitric oxide.

Opioid-induced neuroinflammation plays a role in the development of opioid physical dependence. Moreover, nitric oxide (NO) has been implicated in several oxidative and inflammatory pathologies. Here, we sought to determine whether treatment with venlafaxine during the development of morphine dependence could inhibit naloxone-precipitated withdrawal symptoms. The involvement of neuro-inflammation related cytokines, oxidative stress, and L-arginine (L-arg)-NO pathway in these effects were also investigated. Mice received morphine (50 mg/kg/daily; s.c.), plus venlafaxine (5 and 40 mg/kg, i.p.) once a day for 3 consecutive days. In order to evaluate the possible role of L-arg-NO on the effects caused by venlafaxine, animals received L-arg, L-NAME or aminoguanidine with venlafaxine (40 mg/kg, i.p.) 30 min before each morphine injection for 3 consecutive days. On 4th day of experiment, behavioral signs of morphine-induced physical dependence were evaluated after i.p. naloxone injection. Then, brain levels of tissue necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), brain-derived neurotrophic factor (BDNF), NO and oxidative stress factors including; total thiol, malondialdehyde (MDA) contents and glutathione peroxidase (GPx) activity were determined. Co-administration of venlafaxine (40 mg/kg) with morphine not only inhibited the naloxone-precipitated withdrawal signs including jumping and weight loss, but also reduced the up-regulation of TNF-α, IL-1ß, IL-6, NO and MDA contents in mice brain tissue. However, repeated administration of venlafaxine inhibited the decrease in the brain levels of BDNF, total thiol and GPx. Pre-administration of L-NAME and aminoguanidine improved, while L-arg antagonized the venlafaxine-induced effects. These results provide evidences that venlafaxine could be used as a candidate drug to inhibit morphine withdrawal through the involvement of inflammatory cytokines and l-arginine-NO in mice.

Wound healing effects of topical Vitamin K: A randomized controlled trial.

BACKGROUND: The incidence of acute and chronic wounds has rapidly increased which treatment remains as health problem. Previously, we reported the healing effect of Vitamin K in experimental animal models. The aim of this study was to investigate the effects of topical Vitamin K on skin wound healing process in patients. MATERIALS AND METHODS: Sixty-three patients with indication for high-frequency electrocautery were enrolled in this randomized controlled trial. The patients were divided randomly into three groups. All the patients underwent high-frequency electrocautery treatment. Then, the patients in the A group received 1% Vitamin K cream, the patients in the B group received 1% phenytoin cream. Furthermore, the patients in the control group received Eucerin. The wound status (width and the time of recovery) and complications in the three groups were evaluated 2 weeks after procedure by a dermatologist. RESULTS: The effects produced by the topical Vitamin K showed a significant (P < 0.05) healing when compared with Eucerin group in parameters such as wound contraction and time to full recovery. Moreover, the healing time did not differ between phenytoin and Vitamin K groups (P = 0.16). CONCLUSION: A randomized, controlled trial suggests that topical application of Vitamin K significantly reduces healing time in patients.

Ameliorative effect of gallic acid on sodium arsenite-induced spleno-, cardio- and hemato-toxicity in rats.

AIM: Arsenic is an important toxic chemical affecting millions of people around the world. Exposure to inorganic arsenic results in various health problems including skin lesions, hypertension, hematological disturbance, cardiovascular disease, spleen enlargement and cancer. Gallic acid (GA) is an important phenolic compound possessing various pharmacological properties including anti-inflammatory, antioxidant and free radical scavenging activities. The present study investigated effects of GA against sodium arsenite (SA)-induced spleno-, cardio- and hemato-toxicity. MAIN METHODS: Thirty-five adult male Wistar rats were randomly divided into five groups; group I received normal saline (2 ml/kg/day, p.o.) for 21 days, group II received SA (10 mg/kg/day, p.o.) for 14 days, group III and IV were treated with GA (10 and 30 mg/kg/day, respectively) for 7 days prior to receive SA and treatment was continued up to 21 days in parallel with SA administration, group V received GA (30 mg/kg/day, p.o.) for 21 days. The level of MDA, NO and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase were measured in heart and spleen tissues. Creatine kinase-MB (CK-MB) activity and hematological and histopathological parameters were also assessed. KEY FINDINGS: GA significantly decreased SA-induced elevation of MDA and NO levels and reduction of GSH level and GPx and SOD activity in heart and spleen tissues. Furthermore, GA improved SA-induced alteration in hematological and histopathological parameters and reduced SA-induced elevation of serum CK-MB activity. SIGNIFICANCE: Our results suggest that GA inhibits SA-induced spleno-, cardio- and hemato-toxicity through reducing oxidative stress.

Venlafaxine prevents morphine antinociceptive tolerance: The role of neuroinflammation and the l-arginine-nitric oxide pathway.

Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l-arginine hydrochloride (l-arg) or NO are involved in the effects rendered by VLF, animals were pre-treated with l-arg (200 mg/kg), or the NO synthesis inhibitors N(ω)-nitro-l-arginine methyl ester (L-NAME; 30 mg/kg) or aminoguanidine hydrochloride (AG; 100 mg/kg), along with VLF (40 mg/kg) for three days before receiving morphine for another three days. Nociception was assessed with a hot-plate test on the fourth day, and the concentration of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), interleukin-10, brain-derived neurotrophic factor, NO, and oxidative stress factors such as total thiol, malondialdehyde content, and glutathione peroxidase (GPx) activity in the brain was also determined. Co-administration of VLF with morphine attenuated morphine-induced analgesic tolerance and prevented the upregulation of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6), NO, and malondialdehyde in brains of mice with induced morphine tolerance; chronic VLF administration inhibited this decrease in brain-derived neurotrophic factor, total thiol, and GPx levels. Moreover, repeated administration of l-arg before receipt of VLF antagonized the effects induced by VLF, while L-NAME and AG potentiated these effects. VLF attenuates morphine-induced analgesic tolerance, at least partly because of its anti-inflammatory and antioxidative properties. VLF also appears to suppress the development of morphine-induced analgesic tolerance through an l-arg-NO-mediated mechanism.

Venlafaxine Attenuates the Development of Morphine Tolerance and Dependence: Role of L-Arginine/Nitric Oxide/cGMP Pathway.

BACKGROUND: Severe pain reduces quality of life of patients with various diseases, often because chronic morphine therapy results in reduced analgesic effectiveness, or tolerance, leading to escalating doses and distressing adverse effects. Nitric oxide (NO) plays a role in morphine tolerance and dependence. OBJECTIVE: Venlafaxine, an antidepressant, is known to modulate nitric oxide (NO) pathway in nervous tissues. In the present study, the effect of systemic venlafaxine (VLF) on the development of morphine tolerance and dependence, acute morphine-induced antinociception, and the probable involvement of the L-arginine/NO/cGMP pathway in these effects were investigated in mice. METHODS: Animals developed tolerance to the antinociceptive effect of morphine (50 mg/kg, s.c. daily) for 3 consecutive days. NO modulators like L-NAME (NO synthase inhibitor) and L-Arginine (L-Arg, substrate for NO synthase), sildenafil (cGMP-PDE inhibitor) alone or in combination with venlafaxine were used. RESULTS: The results showed that i.p. administration of VLF (5-40 mg/kg) produced antinociceptive effect in a dose-dependent way. Pretreatment with L-Arg (200 mg/kg, i.p.) reversed the antinociception and L-NAME (30 mg/kg, i.p.) and sildenafil (10 mg/kg, i.p.) potentiated the antinociceptive effect. Moreover, co-administration of VLF in non-effective dose (5 mg/kg) with morphine, potentiated acute morphine-induced analgesia (5 mg/kg, s.c.). This effect was antagonized by L-arginine (200 mg/kg, i.p.) and potentiated by L-NAME (30 mg/kg, i.p.) and sildenafil (10 mg/kg, i.p.). On the other hand, VLF was prevented the development of morphine antinociceptive tolerance and dependence. These effects were antagonized by L-arginine (200 mg/kg, i.p.) and potentiated by L-NAME (30 mg/kg, i.p.) and sildenafil (10 mg/kg, i.p.). CONCLUSION: Our data suggest that the combination of VLF with morphine may be a relevant therapeutic implication to manage pain even when tolerance to morphine exists. Moreover, our data demonstrates the involvement of L-Arg/NO/cGMP pathway in the prevention of morphine tolerance and dependence by venlafaxine.

Red Lentil Extract: Neuroprotective Effects on Perphenazine Induced Catatonia in Rats.

INTRODUCTION: Parkinsonism is a neurodegenerative disease that is defined by certain symptoms such as muscle rigidity, impaired movement, catatonia, tremor and disorientation of body. AIM: The aim was to investigate the effect of red lentil extract on perphenazine-induced Catatonia in model of rat. MATERIALS AND METHODS: This experimental study was done on 48 male albino rats (weight 180-200g) of the Sprague-Dawley strain. Animals were randomly divided into six groups and were pre-treated with a single dose of red lentil extract (200, 400, 800 and 1000 mg/kg), most effective dose of bromocriptine (30mg/kg) and normal saline (5ml/kg) via intraperitoneal (IP) route. perphenazine (5 mg/kg) was after 30 minutes, administered (IP) to induce catatonia. The scoring method of Morpurgo was used to determine the muscular rigidity of animals. RESULTS: The results showed that the 200mg/kg red lentil extract treated group had no significant reduction in catatonic responses after perphenazine administration in comparison with control group while the groups that received 800 and 1000mg/kg of red lentil extract showed significant difference (p<0.05) at all the time points. CONCLUSION: The results revealed that hydroalcoholic extract of red lentil has protective effect on Catatonia induced by perphenazine in rats. So this extract may be probably beneficial for catatonia in Parkinsonism.

Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors.

This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3-10mg/kg) and PGL (1-20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated. Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1-10mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized. These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes.