Therapeutic application of nutraceuticals in diabetic nephropathy: Current evidence and future implications.

Diabetes mellitus (DM) is a common metabolic disease which may cause several complications, such as diabetic nephropathy (DN). The routine medical treatments used for DM are not effective enough and have many undesirable side effects. Moreover, the global increased prevalence of DM makes researchers try to explore potential complementary or alternative treatments. Nutraceuticals, as natural products with pharmaceutical agents, have a wide range of therapeutic properties in various pathologic conditions such as DN. However, the exact underlying mechanisms have not been fully understood. The purpose of this review is to summarize recent findings on the effect of nutraceuticals on DN.

Anti-Degenerative Effect of Melatonin on Intervertebral Disc: Protective Contribution against Inflammation, Oxidative Stress, Apoptosis, and Autophagy.

Intervertebral disc (IVD) degeneration is a leading cause of lower back pain. Although the etiology of IVD degeneration (IVDD) is unclear, excessive oxidative stress, inflammation and apoptosis, and disruption of autophagy play an important role in the pathogenesis of IVDD. Therefore, finding a solution to mitigate these processes could stop or reduce the development of IVDD. Melatonin, a powerful antioxidant, plays an important role in regulating cartilage tissue hemostasis. Melatonin inhibits the destruction of the extracellular matrix (ECM) of the disc. Melatonin preserves ECM contents, including sox-9, aggrecan, and collagen II through inhibiting matrix degeneration enzymes such as MMP-13. These protective effects may be mediated by the inhibition of oxidative stress, inflammation and apoptosis, and regulation of autophagy in IVD cells.

Anti-convulsive Effect of Thiamine and Melatonin Combination in Mice: Involvement of Oxidative Stress.

BACKGROUND: Epilepsy, the second most frequent neurological disease, is a chronic disorder with a high lifetime prevalence. Therefore, various studies are needed to find new effective therapeutic agents to treat seizures or prevent their complications. In this study, we investigated the effects of thiamine, melatonin and their combination on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in mice. METHODS: Male mice were randomly divided into six groups, including control, seizure control, diazepam, melatonin, thiamine and melatonin, and thiamine combination groups. Drugs were given orally in drinking water for 14 days. On the 15th day, the seizure was induced (except the control group) by intraperitoneal injection of PTZ. In all groups, the time between the injection and the start of the seizure (latency), and also the length of the seizure attack (duration), were measured in a 30-minute period. After measuring the latency and duration in all groups, mice were killed by CO2 Box and their brains were dissected to be analyzed for malondialdehyde (MDA) level as a marker of oxidative stress. RESULTS: The seizure duration was significantly lower in the groups of melatonin, thiamine and thiamine and melatonin combination compared to the seizure control group. The latency times in these groups were significantly greater than in the seizure control group. Moreover, MDA concentrations were lower in these groups compared to the seizure control group. CONCLUSION: Thiamine, melatonin and their combination can decrease the duration time of seizure and increase the latency period, which may result from inhibition of oxidative stress in the brain.

Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of COVID-19, is reported to increase the rate of mortality worldwide. COVID-19 is associated with acute respiratory symptoms as well as blood coagulation in the vessels (thrombosis), heart attack and stroke. Given the requirement of angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 entry into host cells, here we discuss how the downregulation of ACE2 in the COVID-19 patients and virus-induced shift in ACE2 catalytic equilibrium, change the concentrations of substrates such as angiotensin II, apelin-13, dynorphin-13, and products such as angiotensin (1-7), angiotensin (1-9), apelin-12, dynorphin-12 in the human body. Substrates accumulation ultimately induces inflammation, angiogenesis, thrombosis, neuronal and tissue damage while diminished products lead to the loss of the anti-inflammatory, anti-thrombotic and anti-angiogenic responses. In this review, we focus on the viral-induced imbalance between ACE2 substrates and products which exacerbates the severity of COVID-19. Considering the roadmap, we propose multiple therapeutic strategies aiming to rebalance the products of ACE2 and to ameliorate the symptoms of the disease.

Melatonin and morphine: potential beneficial effects of co-use.

Morphine is a potent analgesic agent used to control acute or chronic pain. Chronic administration of morphine results in analgesic tolerance, hyperalgesia, and other side effects including dependence, addiction, respiratory depression, and constipation, which limit its clinical usage. Therefore, identifying the new analgesics with fewer side effects which could increase the effect of morphine and reduce its side effects is crucial. Melatonin, a multifunctional molecule produced in the body, is known to play an important role in pain regulation. The strong anti-inflammatory effect of melatonin is suggested to be involved in the attenuation of the pain associated with inflammation. Melatonin also increases the anti-nociceptive actions of opioids, such as morphine, and reverses their tolerance through regulating several cellular signaling pathways. In this review, published articles evaluating the effect of the co-consumption of melatonin and morphine in different conditions were investigated. Our results show that melatonin has pain-killing properties when administered alone or in combination with other anti-nociceptive drugs. Melatonin decreases morphine consumption in different pathologies. Furthermore, attenuation of morphine intake can be accompanied by reduction of morphine-associated side-effects, including physical dependence, morphine tolerance, and morphine-related hyperalgesia. Therefore, it is reasonable to believe that the combination of melatonin with morphine could reduce morphine-induced tolerance and hyperalgesia, which may result from anti-inflammatory and antioxidant properties of melatonin. Overall, we underscore that, to further ameliorate patients' life quality and control their pain in various pathological conditions, melatonin deserves to be used with morphine by anesthesiologists in clinical practice.

Mitochondrial dysfunction in age-related macular degeneration: melatonin as a potential treatment.

Introduction: Age-related Macular Degeneration (AMD), a retinal neurodegenerative disease is the most common cause of blindness among the elderly in developed countries. The impairment of mitochondrial biogenesis has been reported in human retinal pigment epithelium (RPE) cells affected by AMD. Oxidative/nitrosative stress plays an important role in AMD development. The mitochondrial respiratory system is considered a major site of reactive oxygen species (ROS) generation. During aging, insufficient free radical scavenger systems, impairment of DNA repair mechanisms and reduction of mitochondrial degradation and turnover contribute to the massive accumulation of ROS disrupting mitochondrial function. Impaired mitochondrial function leads to the decline in the autophagic capacity and induction of inflammation and apoptosis in human RPE cells affected by AMD.Areas covered: This article evaluates the ameliorative effect of melatonin on AMD and examines AMD pathogenesis with an emphasis on mitochondrial dysfunction. It also considers the potential effects of melatonin on mitochondrial function.Expert opinion: The effect of melatonin on mitochondrial function results in the reduction of oxidative stress, inflammation and apoptosis in the retina; these findings demonstrate that melatonin has the potential to prevent and treat AMD.

Melatonin: new insights on its therapeutic properties in diabetic complications.

Diabetes and diabetic complications are considered as leading causes of both morbidity and mortality in the world. Unfortunately, routine medical treatments used for affected patients possess undesirable side effects, including kidney and liver damages as well as gastrointestinal adverse reactions. Therefore, exploring the novel therapeutic strategies for diabetic patients is a crucial issue. It has been recently shown that melatonin, as main product of the pineal gland, despite its various pharmacological features including anticancer, anti-aging, antioxidant and anti-inflammatory effects, exerts anti-diabetic properties through regulating various cellular mechanisms. The aim of the present review is to describe potential roles of melatonin in the treatment of diabetes and its complications.

Melatonin potentials against viral infections including COVID-19: Current evidence and new findings.

Viral infections are dangerous diseases for human health worldwide, which lead to significant morbidity and mortality each year. Because of their importance and the lack of effective therapeutic approaches, further attempts should be made to discover appropriate alternative or complementary treatments. Melatonin, a multifunctional neurohormone mainly synthesized and secreted by the pineal gland, plays some roles in the treatment of viral infections. Regarding a deadly outbreak of COVID-19 across the world, we decided to discuss melatonin functions against various viral infections including COVID-19. Therefore, in this review, we summarize current evidence on melatonin therapy for viral infections with focus on possible underlying mechanisms of melatonin actions.

Functional parameters, wrist posture deviations and comfort: A comparison between a computer mouse and a touch pen as input devices.

BACKGROUND: Performing common computer tasks such as pointing, clicking, and dragging requires repetitive movements that cause musculoskeletal disorders in the wrists and hands. Given the growing use of touch screens and touch pens, further studies on the ergonomics of these devices are needed. This study aimed to compare a touch pen and an ordinary computer mouse in terms of movement time, error rate, wrist posture, and comfort of use. METHODS: Performance parameters (movement time and error rate), wrist postures, and comfort when using a mouse and a touch pen were measured based on ISO 9241-9 standard with the help of 27 participants. For data analysis, paired t test was performed using SPSS version 22. RESULTS: Using the touch pen resulted in better performance parameters than using the mouse (p < 0.05). Wrist extension and flexion were lower when performing the task with the computer mouse than with the touch pen (p < 0.05). When using the touch pen to perform the task, ulnar deviation and radial deviation were lower (p < 0.05). The overall comfort was higher when using the mouse than the touch pen. CONCLUSION: Our results showed that the touch pen had better performance parameters than the ordinary mouse and also resulted in lower ulnar and radial deviations. Given the impact of habit and proficiency on users' comfort in using input devices, it is reasonable to expect users becoming more comfortable by using touch pens on the long term.

Melatonin in the treatment of fibromyalgia symptoms: A systematic review.

The available pharmacological modalities for the treatment of fibromyalgia (FM) are associated with a variety of adverse effects and limited benefits. In this study, we systematically reviewed the impact of melatonin in the treatment of FM. Interventional studies, either controlled or uncontrolled and randomized or non-randomized, were included. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched without time limitation. Primary outcome measures were the effect of melatonin on the disease impact, pain, sleep quality, tender point count, fatigue, anxiety, stiffness, and depression in FM patients. Four studies, reporting the effect of melatonin on 98 patients, were eligible to include. All the studies reported the positive effect of melatonin on the FM symptoms. No major adverse event was reported. A significant level of heterogeneity was observed between the studies. Therefore, further high-quality controlled clinical trials are needed to understand the role of melatonin in FM treatment fully.

Ergonomic intervention to reduce musculoskeletal disorders among flour factory workers.

BACKGROUND: Work-related musculoskeletal disorders are the most common occupational health hazards. In the flour production industry, the fast pace of work, high frequency of repetitive movements, manual handling of loads, and awkward postures put a lot of pressure on the worker's body. OBJECTIVE: Given the high exposure of the workers of the flour production industry to ergonomic risk factors, this study aimed to reduce the rate of musculoskeletal disorders among a group of flour factory workers through ergonomic interventions. MATERIALS AND METHODS: This interventional study was performed using the census method on the eligible workers of a flour factory. An ergonomic intervention program was planned and implemented with the goal of reducing musculoskeletal disorders. The effectiveness of the program was evaluated by measuring the prevalence of musculoskeletal disorders before and six months after the interventions. RESULTS: Before the intervention, musculoskeletal disorders were most prevalent in the lower back, arms, shoulders, legs, thighs, knees, neck and wrists, respectively. Evaluation of the prevalence of musculoskeletal disorders after the intervention showed the positive effect of the ergonomic intervention program on musculoskeletal disorders in the neck, shoulders, lower back, thighs, knees, and legs (P < 0.05). CONCLUSION: Engineering and management interventions implemented in this study led to a significant reduction in the level of ergonomic risk factors and a reduced rate of musculoskeletal disorders among workers of different units in the flour factory.

Idiopathic pulmonary fibrosis (IPF) signaling pathways and protective roles of melatonin.

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive loss of lung function due to tissue scarring. A variety of pro-inflammatory and pro-fibrogenic factors including interleukin­17A, transforming growth factor ß, Wnt/ß­catenin, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factors, endotelin­1, renin angiotensin system and impaired caveolin­1 function are involved in the IPF pathogenesis. Current therapies for IPF have some limitations and this highlights the need for effective therapeutic agents to treat this fatal disease. Melatonin and its metabolites are broad-spectrum antioxidants that not only remove reactive oxygen and nitrogen species by radical scavenging but also up-regulate the expression and activity of endogenous antioxidants. Via these actions, melatonin and its metabolites modulate a variety of molecular pathways in different pathophysiological conditions. Herein, we review the signaling pathways involved in the pathophysiology of IPF and the potentially protective effects of melatonin on these pathways.

Effectiveness of Stellate Ganglion Block Under Fuoroscopy or Ultrasound Guidance in Upper Extremity CRPS.

INTRODUCTION: Stellate Ganglion Block (SGB) is an effective technique which may be used to manage upper extremities pain due to Chronic Regional Pain Syndrome (CRPS), in this study we tried to evaluate the effectiveness of this procedure under two different guidance for management of this syndrome. AIM: The purpose of this study was to evaluate the effectiveness of ultrsound guide SGB by comparing it with the furoscopy guided SGB in upper extermities CRPS patients in reducing pain & dysfuction of the affected link. MATERIALS AND METHODS: Fourteen patients with sympathetic CRPS in upper extremities in a randomized method with block randomization divided in two equal groups (with ultrasound or fluoroscopic guidance). First group was blocked under fluoroscopic guidance and second group blocked under ultrasound guidance. After correct positioning of the needle, a mixture of 5 ml bupivacaine 0.25% and 1 mL of triamcinolone was injected. RESULTS: These data represent no meaningful statistical difference between the two groups in terms of the number of pain attacks before the blocks, a borderline correlation between two groups one week and one month after the block and a significant statistical correlation between two groups three month after the block. These data represent no meaningful statistical difference between the patients of any group in terms of the pain intensity (from one week to six months after block), p-value = 0.61. These data represent a meaningful statistical difference among patients of any group and between the two groups in terms of the pain intensity (before the block until six months after block), p-values were 0.001, 0.031 respectively. CONCLUSION: According the above mentioned data, in comparison with fluoroscopic guidance, stellate ganglion block under ultrasound guidance is a safe and effective method with lower complication and better improvement in patient's disability indexes.

Helicobacter pylori eradication effect on patients with functional dyspepsia symptoms.

BACKGROUND: Dyspepsia is a common symptom with a broad differential diagnosis and complex pathophysiology which annually affect about 25% of the general population. Results of Helicobacter pylori eradication in the patients with dyspepsia symptoms in the different studies are controversy. Aim of the study was to evaluate the effect of Helicobacter pylori eradication in the patients with functional dyspepsia. METHODS: In order to doing the clinical trial study, demographic and clinical symptoms of the patients that referred to the gastroenterology center of the Ilam County from 1391 to 1392 was recorded in a standard questionnaire (including criteria of ROM III). Overall 120 patients with dyspepsia were selected and divided into two groups of "control" and "treatment". Helicobacter pylori presence was confirmed by stool antigen test in all of the patients. Selected patients were randomly divided into two groups. Standard therapy for the Helicobacter pylori eradication was done for two weeks periods in the one group. Then in this group antacid medication (morning and night) was continued. Four weeks treatment with antacid medication (morning and night) was performed for second group (control) and then both groups were treated with antacid for three month and both groups were finally evaluated with same questionnaire. RESULTS: The mean age of patients was 32 years; 55.8% of the patients were female. The most prevalent symptoms of functional dyspepsia (25.7%) were in the age groups of 16-34 years and 35-43 years. All of dyspepsia symptoms in the both groups of cases (Helicobacter pylori standard treated) and control (treated with antacid) decreased after treated. However, this reduction in all symptoms was not significant except for epigastric pain and vomiting. CONCLUSIONS: Helicobacter pylori eradication has a little effect in improving of the functional dyspepsia syndrome and the effect was justly seen in the symptoms of epigastric pain and vomiting.

The Incidence of Severe Diarrhea with Transdermal Fentanyl Patch: An Uncommon Event.

Cancer pain is a major problem for the health care providers. One of the most important aspects of cancer pain is palliative care management. Recently, different research finding shows the efficacy of opioid analgesics such as fentanyl transdermal patch in chronic pain management. Transdermal Fentanyl patches may cause side effects such as drowsiness, dizziness, itching, life-threatening or serious breathing difficulties and diarrhea, mainly during the first 72 h of patient's treatment initiation and any time when the drug's dose is increased. We report three case reports of severe diarrhea without most common side effects associated with Fentanyl patches during first 72 h of patient's treatment.

Efficacy of fentanyl transdermal patch in the treatment of chronic soft tissue cancer pain.

BACKGROUND: Cancer pain may be a major problem for health care providers worldwide. According to different studies reporting the pain severity, one-third of patients reported to have moderate to severe pain. Management of cancer pain is one of the most important goals of palliative care. Recently, different research results on the efficacy of opioid analgesics in chronic pain management have played a role to implement standards in pain control by government agencies worldwide. OBJECTIVES: This study aimed to investigate the efficacy of fentanyl transdermal patch in the treatment of chronic soft tissue cancer pain. PATIENTS AND METHODS: In a prospective descriptive study, we evaluated 86 patients with soft tissue tumors with chronic pain referred to cancer institute of Imam Khomeini Hospital, Tehran, Iran, during 2006-2007. For all patients, transdermal fentanyl patch (25 µg/h) was administered. The appearance of patches was the same. Pain severity was measured by Visual Analogue Scale (VAS) initially and 24, 48 and 72 hours after the initiation of treatment. RESULTS: Patients' characteristics and VAS score before the treatment were not significantly different (P > 0.05). According to our findings, the pain severity was significantly reduced after the treatment (P = 0.001). The incidence of adverse events in patients was significantly high (72%). The most common adverse events were sleepiness, nausea and vomiting in 30.2% and 18.6%, respectively. CONCLUSIONS: Transdermal fentanyl patch was an effective and safe method to reduce pain in patients with soft tissue tumors. Moreover, it could improve the quality of life in these patients, but adverse events occurred in approximately 72% of patients.

A 7-Years Retrospective Study of Gastrointestinal Cancers Incidence in the Western Iran.

INTRODUCTION: In Iran, cancer is the third reason of the death and every year 500,000 new cases were detected, and 14% of all death is related to cancer. The most common system that is affected by cancer (after the skin) is gastrointestinal (GI) system. The purpose of the study is evaluation of the 7 years incidence (2002-2008) of the GI cancers in Ilam province in the west of Iran. MATERIALS AND METHODS: In this retrospective cross-sectional study, total 307 record health related to the patients affected by the gastro-intestinal system cancer were evaluated after referring to the pathologic centers of the Ilam province and neighboring provinces. Patient's data were recorded from their file based on the standard questionnaire. RESULT: The mean age ± standard deviation of participants was 63.8+1.5. More than half of participants study was men (58.3%). The prevalence of the esophagus, stomach, small intestine and colorectal cancers was significantly higher in the men than the women (unlike liver cancer) (p<0.001). The most common site of GI cancer were esophagus (38.1%) and stomach (34.2%) but small intestine was allocated the least prevalence (1%) to itself. The most common pathology type of cancer was adenocarcinoma in the GI system (68.1%). CONCLUSION: According to the high prevalence of the GI cancer and also the ascending incidence of the patient with disease in the Ilam province, special measures should be considered for the reduction of the life and property load resulted from this disease. People by introduction of the warning signs of the gastrointestinal system cancer should be screened for GI cancer.

Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report.

Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy.

Celiac disease prevalence in the patients with irritable bowel syndrome in the ilam province; a cross sectional study from Western iran.

INTRODUCTION: Many studies have shown that the prevalence of celiac disease (CD) is increasing in the patients with irritable bowel syndrome (IBS), but the present evidences are controversy and all of the researches don't suggest evaluation of the patients with IBS for the CD. MATERIALS AND METHODS: In the cross-sectional study, 1000 patients that affected by IBS with the predominant feature of diarrhea who referred to the gastroenterology clinic were evaluated during 2009-2012 years. Blood samples were taken from the patients for ELISA of IgA tissue transglutaminase (TTG) Ab. Then biopsy was taken from the second part of duodenum of all of patients by endoscopy and the sample was referred to pathologist for histopathology evaluation in order to confirm diagnosis. RESULTS: About half of the patients with IBS were women (50.3%) and the mean age ± Standard deviation of the men and women was 29.59±11.41 and 28.42±11.73, respectively. The mean titer of TTG IgA Ab in the women and men affected by IBS was 5.25±17.77 and 7.22±25.4, respectively. Seventy six cases (7.6%) that affected by IBS had high serum level of Ab titer (TTG IgA.Ab≥10) that including 41 women and 35 men. In the patients with high serum level of Ab titer, 57 cases (75%) were affected by celiac disease (based on histopathology report). Therefore, the prevalence of CD was 5.7% among patients with IBS. CONCLUSION: In the current study the incidence of CD was evaluated 5.7 cases per each 100 people with IBS. It's suggested that all of the patients with diarrhea predominant IBS and high serum level of TTG IgA Ab must be examined for evaluation of CD.

Associated factors with male infertility: a case control study.

OBJECTIVE: Sperm analysis is an important step to evaluate and diagnose male's infertility. The present study aimed to determine associated factors with males' infertility by using semen analysis. MATERIALS AND METHODS: In this study 96 men were evaluated who attended to the infertility clinics of Ilam province, western Iran between May 2010 to May 2011. Semen analysis was done using the Weili Dynamic Sperm Analysis software adapted to the WHO classification. Based on movement and speed characters, sperms were classified to either A, B, C or D classes. Participants were stratified into two groups that called "Oligospermia (OS)" with sperm counts of less than 20 million in mL (n=48) and "Non-Oligospermia (NOS)" with values more than determined cutoff point (n=48). RESULTS: The Mean age ±SD for OS and NOS group were 29.9 ±5.1 y and 31.17 ±5.24 y, respectively (p>0.05). Overall, 62.5% of OS and 31.2% of NOS were clinically infertile (OR=3.6, CI, 1.5-8.5, p=0.01). A significant difference was found between job and live ratio(A+B+C) in NOS group (F=2.8, p<0.05). CONCLUSION: Prevalence of infertility was higher in the OS men compared to the NOS group. The main risk factors in the OS group were History of Varicocele surgery and residence site of patients that are totally similar to the NOS men. Further case-control studies and clinical trials are recommended to recognize infertility causes in men.