Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy.

STUDY DESIGN: This is an animal study. OBJECTIVES: Metformin is a safe drug for controlling blood sugar in diabetes. It has been shown that metformin improves locomotor recovery after spinal cord injury (SCI). Neuropathic pain is also a disturbing component of SCI. It is indicated that metformin has neuroprotective and anti-inflammatory effects, which attenuate neuropathic pain and hyperalgesia in injured nerves. Thus, we evaluated metformin's therapeutic effects on SCI neuroinflammation and its sensory and locomotor complications. Meanwhile, results were compared to minocycline, an anti-neuroinflammation therapy in SCI. SETTING: Experimental Medicine Research Center, Tehran University of Medical Sciences, Iran METHODS: In an animal model of SCI, 48 male rats were subjected to T9 vertebra laminectomy. Animals were divided into a SHAM-operated group and five treatment groups. The treatments included normal saline as a vehicle control group, minocycline 90 mg/kg and metformin at the doses of 10, 50 and 100 mg/kg. Locomotor scaling, behavioral tests for neuropathic pain and weight changes were evaluated and compared through a 28-days period. At the end of the study, tissue samples were taken to assess neuroinflammatory changes. RESULTS: Metformin 50 mg/kg improved the locomotors ability (p < 0.001) and decreased sensitivity to mechanical and thermal allodynia (p < 0.01). These results were compatible with minocycline effect on SCI (p > 0.05). While metformin led to weight loss, both metformin and minocycline significantly decreased neuroinflammation in the assessment of cord tissue histopathology, and levels of TNF-α and interleukin-1ß (p < 0.001). CONCLUSIONS: Metformin could be considered as an alternative therapeutic agent for SCI, as it potentially attenuates neuroinflammation, sensory and locomotor complications of cord injury.

The effects of Alkanna tinctoria Tausch on split-thickness skin graft donor site management: a randomized, blinded placebo-controlled trial.

BACKGROUND: A prospective, randomized, placebo-controlled clinical trial was conducted to compare the healing effectiveness of Alkanna tinctoria (L.) Tausch (Boraginaceae) with standard dressing on wound healing at the donor site after removal of the skin graft. METHODS: Enrolled patients were randomly allocated to receive topicalA. tinctoria extract ointment (20%) or standard dressing (dressing with base ointment) daily. Wound healing was assessed using the Bates-Jenson assessment tool at the 2nd and 4th weeks after intervention. RESULTS: Decreases in wound score were significantly greater in the A. tinctoria group compared with the placebo group (P <0.05). The surface areas of graft donor sites in the A. tinctoria group were significantly reduced as compared with the control group at day 28 of the intervention (P < 0.05). The proportion of patients in the A. tinctoria group achieving complete wound healing within 2 to 4 weeks was 50% and 96.66%, respectively, significantly higher than in patients receiving standard care: 0% and 23.3%, respectively. CONCLUSIONS: This clinical study showed that A. tinctoria dressing accelerates wound healing after graft harvesting. TRIAL REGISTRATION: IRCT ID: IRCT201511165781N2 .

Antinociceptive and antidiarrheal effects of pioglitazone in a rat model of diarrhoea-predominant irritable bowel syndrome: role of nitric oxide.

Irritable bowel syndrome (IBS) is a prevalent disease characterized by abdominal pain and abnormal bowel habits. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR) γ agonist and, although it is mostly used as an antidiabetic agent, it has been reported to have analgesic effects. Nitric oxide (NO), a gaseous molecule that mediates many of the effects of pioglitazone, has been implicated in the pathophysiology of IBS. The aim of the present study was to investigate the effects of pioglitazone on symptoms in a rat model of diarrhoea-predominant IBS (D-IBS).and to determine the role of NO in these effects. Diarrhoea-predominant IBS was induced by intracolonic instillation of acetic acid. Pioglitazone (2 mg/kg, i.p.) was administered on Days 7, 9 and 11 after acetic acid instillation. To investigate the mechanism involved in pioglitazone action, rats were also administered either the PPARγ antagonist GW9662 (3 mg/kg, i.p.), the NO synthase (NOS) inhibitor N(G) -nitro-l-arginine methyl ester (l-NAME; 10 mg/kg, i.p.) or the NO precursor l-arginine (250 mg/kg, i.p.) along with pioglitazone. Visceral hypersensitivity, nociceptive thresholds, defecation frequency, stool form, serum and colon NO production and inducible (i) NOS activity were assessed 1 h after the final injection of pioglitazone or dimethylsulphoxide (used as the vehicle). Pioglitazone reduced visceral hypersensitivity and defecation frequency, increased nociceptive thresholds, NO production and iNOS activity and shifted stool form towards hard stools in D-IBS rats. These effects of pioglitazone were significantly reversed by l-NAME, but not GW9662. l-Arginine augmented the effects of pioglitazone. In conclusion, pioglitazone alleviates symptoms in a rat model of D-IBS through an NO-dependent mechanism.

Evaluation of bone mineral loss in patients with chronic traumatic spinal cord injury in Iran.

OBJECTIVES: We described the associations between demographic and injury-related factors on bone mineral density (BMD) of the spine and the hip among adult patients with chronic spinal cord injury (SCI). DESIGN: BMD in spinal and femoral bone sites were assessed. Multivariate analysis was performed to evaluate the relationship between anthropometric and injury-related factors with BMD. Serum level and amount of dietary intake of calcium, phosphor, and 25-hydroxy vitamin D were measured. SETTING: A referral tertiary rehabilitation center in Iran. PARTICIPANTS: Patients with SCI who had no previous history of endocrine disorders and were not on specific medications entered the investigation. Those with non-traumatic SCI, pregnant, or with substance dependency were excluded as well. INTERVENTIONS: No interventions were applied. MAIN STUDY OUTCOME MEASURES: Dual X-ray absorptiometry was performed to estimate BMD. Body mass index was positively associated with higher femoral (P < 0.01, r = 0.56) and hip (P < 0.0001, r = 0.82) BMD only in female participants. The high prevalence of vitamin D deficiency (60%) was noticeable. RESULTS: Older male patients revealed lower BMD only in spinal vertebrae (P < 0.02, r = -0.21). A significant higher BMD loss in lumbar vertebras in male patients with complete spinal cord lesion (P < 0.009) was detected. Spinal reduction of BMD was more severe when the level of injury was above T6 (P < 0.02). CONCLUSION: Along with the clarification of age, gender, post injury duration, and the other factors' effect on the BMD in the SCI patients, here we have also shown the noticeable prevalence of the 25-hydoxy vitamin D deficiency in these patients which needs attention.

Calcium and vitamin D plasma concentration and nutritional intake status in patients with chronic spinal cord injury: A referral center report.

BACKGROUND: Nutritional status influences bone health spinal cord injury (SCI). This study evaluates serum levels of 25-hydroxy-vitamin-D and calcium along with dietary intakes in patients with chronic SCI. MATERIALS AND METHODS: Total of 160 patients participated in this investigation. Dietary intakes were assessed by semi-quantitative food-frequency questionnaire. Serum calcium, phosphorus and 25(OH)-vitamin-D level were measured. RESULTS: Mean of serum calcium and 25(OH)-vitamin-D were 9.54 ± 0.64 mg/dl (standard error of the mean [SE]: 0.05) and 13.6 ± 10.99 µg/dl (SE: 0.9), respectively. Dairy intake was below recommended amount (1.8 ± 0.74 per serving (SE: 0.06), recommended: 4). A high prevalence (53.1%) of Vitamin D deficiency (25(OH) Vitamin D <13 ng/ml) was found. CONCLUSION: This study shows below adequate intake of calcium and Vitamin D in Iranian patients with SCI. These results insist on the importance of dietary modifications among these patients.

Descriptive epidemiology: prevalence, incidence, sociodemographic factors, socioeconomic domains, and quality of life of epilepsy: an update and systematic review.

INTRODUCTION: The purpose of this study was to investigate the contributions of quality of life (QOL), sociodemographic factors (age, sex, etc.), residential areas, general attitudes toward epilepsy, socioeconomic domains, prevalence and incidence in epileptic patients from Iran. MATERIAL AND METHODS: A systematic literature search was conducted, including database searches in PubMed, Medline, Embase, ScienceDirect, Scopus, ISC, Health, Web of Science, and the Cochrane Library Database of relevant articles, personal files and systematic reviews to identify studies examining risk factors in epilepsy. RESULTS: This review article shows that certain socio-demographic and socio-economic factors, geographic variation in epidemiologic patterns of epilepsy as well as clinical factors may be crucial in determining QOL in epilepsy patients and provides further evidence supporting the validity of the scale in QOL based on consideration of different target groups in different areas. CONCLUSIONS: Prevalence of epilepsy appears to be correlated with socioeconomic status in the lower socioeconomic groups. Also demographic characteristics, socio-economic factors and clinical presentation are linked to different QOL of these patients among nations. The educational program has a beneficial effect on self-management behaviors in patients with epilepsy. More work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of people with epilepsy.

The effect of behavioral intervention and nutrition education program on serum lipid profile, body weight and blood pressure in Iranian individuals with spinal cord injury: A randomized clinical trial.

OBJECTIVE: The efficacy of nutrition education on body weight and serum lipids has not yet been described in patients with spinal cord injury (SCI). In the present study, we examined the effect of a 7-month nutrition education program on lipid profile and body weight in individuals with SCI. DESIGN: Randomized clinical trial. SETTING: A tertiary rehabilitation center. PARTICIPANTS: Patients with SCI who were referred to Brain and Spinal Cord Injury Research Center. INTERVENTION: The nutrition education program consisted of 5 education sessions during a period of 7 months. OUTCOME MEASURES: Body weight and serum concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measure at the beginning of the trial and after 7 months. Two-way repeated measure analysis of variance (ANOVA) was used. RESULTS: Total of 57 patients (27 in control group and 30 in education group) participated. Nutrition education program showed no significant effect on the levels of TC, TG, LDL-C and HDL-C (P: 0.224, 0.172, 0.107 and 0.081, respectively). No significant changes in weight and waist circumflex have been observed as well (P: 0.970 and 0.361, respectively). CONCLUSION: Our findings do not support a significant influence of nutrition education program on weight and lipid profile. It seems that the nutrition education program alone is not adequately effective to have beneficial influence on weight and lipid profile. Clinical trial registration No.: IRCT201406215968N3.

Is the pattern of dietary amino acids intake associated with serum lipid profile and blood pressure among individuals with spinal cord injury?

OBJECTIVE: The probable effect of dietary amino acids intake pattern on serum lipid profile and blood pressure (BP) have not yet been described among individuals with spinal cord injury (SCI). DESIGN: Cross-sectional. SETTING: Tertiary rehabilitation center. PARTICIPANTS: People with SCI referred to Brain and Spinal Cord Injury Research Center between 2011 and 2014. OUTCOME MEASURES: Dietary intakes were assessed by recording consumed foods by 24-hour dietary recall interviews using Nutritionist IV 3.5.3 modified for Iranian foods. Partial correlation test with adjustment for age, weight, body mass index, total energy intake, total fat, cholesterol and carbohydrate intake, and injury-related variables was used. RESULTS: Dietary intake of lysine was positively related to levels of fasting plasma glucose (FPG), triglyceride (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P < 0.0001, 0.046, 0.002 and 0.009, respectively). There was a positive significant relationship between the intake of cysteine and levels of TG and SBP as well (P : 0.027 and 0.048, respectively). Higher intakes of threonine and leucine had a negative relationship with TG level (P : 0.001 and 0.026, respectively). Furthermore, tyrosine, threonine and leucine were inversely correlated to blood pressure. Total cholesterol level was only related to intake of threonine and leucine (P : 0.004 and 0.012, respectively). FPG was positively associated with intake of all amino acids except for cysteine, glutamic acid, threonine, leucine and histidine. CONCLUSION: In the present study, the pattern of relationships between dietary intake of amino acids and serum lipid profile and BP has been described among people with SCI.

Dietary pattern as identified by factorial analysis and its association with lipid profile and fasting plasma glucose among Iranian individuals with spinal cord injury.

OBJECTIVES: Plasma lipids (triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C)) may be associated with dietary intakes. The purpose of this study was to identify the most common food patterns among Iranian persons with spinal cord injury (SCI) and investigate their associations with lipid profile. DESIGN: Cross-sectional. SETTING: Tertiary rehabilitation center. PARTICIPANTS: Referred individuals to Brain and Spinal Injury Research Center (BASIR) from 2011 to 2014. OUTCOME MEASURES: Dietary intakes were assessed by 24-hour dietary recall interviews in three non-consecutive days. Principal component analysis (PCA) was used to identify dietary patterns. RESULTS: Total of 100 persons (83 male and 17 female) entered the study. Four food patterns were detected. The most common dietary pattern (Pattern 1) included processed meat, sweets desserts and soft drink and was similar to 'Western' food pattern described previously. Pattern 1 was related to higher levels of TC and LDL-C (r = 0.09; P = 0.04 and r = 0.11; P = 0.03 for TC and LDL-C, respectively) only in male participants. Pattern 2 which included tea, nuts, vegetable oil and sugars had a positive association with TC level (r = 0.11; P = 0.02) again in male participants. Pattern 3 which represented a healthy food pattern showed no significant influence on lipid profiles. CONCLUSION: In this study, the four most common dietary patterns among Iranian individuals with SCI have been identified. Western food pattern was the most common diet and was associated with increased TC and LDL-C. The healthy food pattern, in which the major source of calories was protein, was not associated with variance in lipid profile.

Assessment of Attention to Clothing and Impact of Its Restrictive Factors in Iranian Patients with Traumatic Spinal Cord Injury (ACIRF-SCI): Introduction of a New Questionnaire.

BACKGROUND: Patients with spinal cord injury (SCI) deal with various restrictive factors regarding their clothing, such as disability and difficulty with access to shopping centers. OBJECTIVE: We designed a questionnaire to assess attention to clothing and impact of its restrictive factors among Iranian patients with SCI (ACIRF-SCI). METHODS: The ACIRF-SCI has 5 domains: functional, medical, attitude, aesthetic, and emotional. The first 3 domains reflect the impact of restrictive factors (factors that restrict attention to clothing), and the last 2 domains reflect attention to clothing and fashion. Functional restrictive factors include disability and dependence. Medical restrictive factors include existence of specific medical conditions that interfere with clothing choice. Construct validity was assessed by factorial analysis, and reliability was expressed by Cronbach's alpha. RESULTS: A total of 100 patients (75 men and 25 women) entered this study. Patients with a lower injury level had a higher total score (P < .0001), and similarly, patients with paraplegia had higher scores than those with tetraplegia (P < .0001), which illustrates an admissible discriminant validity. Postinjury duration was positively associated with total scores (r = 0.21, P = .04). Construct validity was 0.97, and Cronbach's alpha was 0.61. CONCLUSIONS: Iranian patients with SCI who have greater ability and independence experience a lower impact of restrictive factors related to clothing. The ACIRF-SCI reveals that this assumption is statistically significant, which shows its admissible discriminant validity. The measured construct validity (0.97) and reliability (internal consistency expressed by alpha = 0.61) are acceptable.

Safety and Efficacy of PDpoetin for Management of Anemia in Patients with end Stage Renal Disease on Maintenance Hemodialysis: Results from a Phase IV Clinical Trial.

Recombinant human erythropoietin (rHuEPO) is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2) years. 48.7% of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43) g/dL at beginning of the study and reached 10.96 (±2.23) g/dL after 4 months and showed significant increase overall (P<0.001). PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL). Anemia were successfully corrected in 49% of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis.

Lithium protects against spinal cord injury in rats: role of nitric oxide.

OBJECTIVE: Lithium improves locomotor scores after spinal cord injury (SCI) in rats. However, the underlying mechanisms are unknown. Herein, we assess the role of nitric oxide (NO) in this action. METHODS: The first set of experiments were performed to determine a dose of lithium that effectively improves locomotor scores in rats with SCI. Therefore, rats received different doses of lithium chloride (1, 4, 10, and 20 mg/kg intraperitoneally) or saline 1 hour before SCI. In the next step, the role of NO in the effect of lithium on SCI was investigated. For this purpose, rats were co-treated with an effective dose of lithium (20 mg/kg 1 hour before SCI) and a noneffective dose of Nω-nitro-L-arginine methyl ester (L-NAME, a nonselective NO synthase inhibitor; 15 mg/kg intraperitoneally 30 minutes before SCI). SCI was induced by compressing the T9 spinal segment with an aneurysmal clip for 60 seconds in anesthetized rats. Locomotor scores were determined at 1, 3, 5, 7, 14, 21, and 28 days after SCI. Plasma lithium levels were measured 12 hours after SCI. Spinal histopathologies were examined 30 days after SCI. RESULTS: Lithium (20 mg/kg) significantly improved locomotor scores and decreased histopathologic spinal damage. l-NAME (15 mg/kg) reversed the beneficial effects of lithium. The 20-mg/kg dose of lithium resulted in a 0.68 ± 0.02 mEq/L plasma lithium concentration, which is lower than the therapeutic level in humans (0.8-1.2 mEq/L). CONCLUSION: Lithium protects against SCI through an NO-dependent mechanism.

Cardiometabolic risk factors in Iranians with spinal cord injury: analysis by injury-related variables.

Persons with spinal cord injury (SCI) have a high prevalence of abnormalities in carbohydrate and lipid metabolism. These abnormalities cause adverse coronary heart disease (CHD) in patients with SCI. In this study, we performed a detailed analysis of the level-specific cardiometabolic risk factors in individuals with SCI and analyzed the association of injury level on these risk factors. This was a cross-sectional study of 162 patients with SCI, assessing the prevalence of diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking. Fasting blood sugar (>100) was diagnosed in 27 patients (16.7%). Of the total patients, 36 (22.2%) had a total cholesterol (TC) level of >200. A triglyceride level of >150 was present in 56 patients (34.6%). Hypertension was present in 2.5% of the entire patient group. Body mass index (BMI), TC, and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the paraplegia group than the tetraplegia group (24.44 +/- 4.23 vs 22.65 +/- 4.27, p = 0.01; 185.71 +/- 40.69 vs 163.28 +/- 37.92, p < 0.001; and 102.51 +/- 28.20 vs 89.15 +/- 22.35, p = 0.01, respectively). Patients with paraplegia may have increased hypertension, higher BMI, and increasing levels of serum LDL-C and TC than those with tetraplegia. Conventional risk factors for CHD should be identified and treated in individuals with SCI.