Application of methylene blue for the prevention and treatment of COVID-19: A narrative review.

The newest virus from the SARS family of viruses called acute syndrome-coronavirus-2 (SARS-CoV-2), which causes COVID-19 disease, was identified in China at the end of 2019. In March 2020, after it spread to 29 additional countries, it was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 infection mainly starts through the respiratory tract and causes a wide spectrum of symptoms from asymptomatic infections to acute respiratory distress syndrome with multi-organ failure and vasoplegic shock. Among the many immunomodulatory and antiviral drugs that have been studied for the treatment of COVID-19, methylene blue (MB) may play an influential role. This article reviews the history of MB applications, the antiviral effects of MB against SARS-CoV-2, and the results of in vivo and in vitro studies of the use of MB in COVID-19. Based on studies, MB can simultaneously affect most of the host's harmful responses caused by SARS-CoV-2 infection due to its multiple properties, including anti-hypoxemia, anti-oxidant, immune system modulator, and antiviral. The use of MB is associated with a reduction in the possibility of getting infection, and mortality, and can be used as a safe, effective, cheap, and available treatment option with minimal side effects for the clinical management of COVID-19.

Penile Enhancement Using Biodegradable Scaffolds Covered with Platelet-rich Plasma-Fibrin Glue, Mesenchymal Stem Cells for Micropenis.

PURPOSE: Evaluation of preliminary cosmetic and functional outcomes of biodegradable scaffolds covered with platelet-rich plasma in penile girth augmentation. MATERIALS AND METHODS: Between June 2016 and June 2018, 36 males who had a mean age of 28.91 years (range 20 - 48 years) with micropenis underwent this procedure. A mixture of platelets-fibrin glue and mesenchymal cells obtained from dermal fat tissue were prepared. Then the mixture was seeded on the pretreated tube-shaped poly lactic-co-glycolic acid scaffold and underwent a whole day of incubation. Following penile degloving, scaffolds were surgically implanted within the interface region of dartos and Buck's fascia. The 5-point Likert scoring scale was used to evaluate the patients' satisfaction with surgery. RESULTS: Patients followed up for 6-12 (8 ± 2.86) months. The penile length in an erected state before surgery was 6.5 - 12.5 cm (9.08 ± 1.6) which enhanced to 7 - 14 cm (10.59 ± 1.71) after surgery (P < .0001). The penile girth before and after surgery were 8.49 ± 1.53 and 10.91 ± 1.96 cm, respectively (P < .0001). An augment in penile length and girth of 1.5 and 2.6 cm were achieved, respectively. Patients appraised surgical intervention on a rating of one to five. The highest possible score (5) was assigned by 27 %, 33 % expressed a very good mark (4), and 19 % gave a good mark (3). CONCLUSION: Covering the scaffold with a mixture of Platelets-Fibrin glue and mesenchymal cells seems a safe and feasible method for penile reconstruction surgery. More studies should be done to determine the effect of platelets- fibrin glue and mesenchymal cells for treating micropenis.

Mixed treatment for same-severe mixed urinary incontinence: A novel method.

Key Clinical Message: Innovative mixed treatment offers hope for persistent mixed urinary incontinence (MUI): PRP-Fibrin Glue-Stem Cell injection, Botox, and TVT in a single session. Successful case study reveals promising outcomes, emphasizing the need for further research. Abstract: Mixed urinary incontinence is a complaint of stress and urge incontinence which affects patients' quality of life and dramatic changes in patients' physical, mental, and socioeconomic status. The treatment is challenging and depends on the dominance of one of the complaints to the other. The progress in the method of treatment is still under discussion. This study reports treatment of a MUI case in a 56-year-old, with a history of MUI of 7-year duration, which was persistent to pharmacological treatment, pelvic muscle training, biofeedback, and anti-incontinence surgery (Burch Colposuspension). PRP-Fibrin Glue-Stem Cell injection, Botox injection, and TVT were performed in a one surgery session. Patient was discharged with ability to urinate with acceptable amount of post void residue. After 3-month follow-up, patient was completely satisfied and happy. Further research is needed to substantiate the efficacy of these mixed treatments for MUI.

Complete Salvage of Third-degree Burn of Ear by Repairing Gel-PRP-Fibrin Glue, A Case Report.

The ear is a very important facial feature and enhances the overall look of the face. Usually, patients with entire ear burns also have large areas of burn in their bodies. To save the patient, skin grafting to reduce the injured body surface area is prioritized and the treatment of the ears may be inevitably delayed, which results in minor to very severe cosmetic deformity. This has a deep effect on the life quality of a patient who survives a burn injury. Therefore, any step that decreases ear deformity or loss is very crucial for the patient. There are different challenging procedures for ear reconstruction which are very tedious works. In this study, for one patient, repairing gel-platelet-rich plasma-fibrin glue was applied for the treatment of a deep dermal burned ear as a novel, non-invasive, and simple approach to give a normal shape to the ear to prevent extensive morbidity during the acute phase and deformities later as a consequence of burns. No keloid is observed after treatment.

Limb Saving with a Combination of Allogenic Platelets-Rich Plasma, Fibrin Glue, and Collagen Matrix in an Open Fracture of the Tibia: A Case Report.

Tibia open fractures and lower limb soft tissue injuries are undesired conditions for orthopedic and general surgeons, and there is no ideal procedure for treating recalcitrant ulcers or severe traumatic ulcers. Recently, several novel approaches have been proposed, such as bone marrow stem cells, platelets, fibrin glue, and collagen matrix. The current study was conducted to evaluate the effectiveness of combining platelets, fibrin glue, and a collagen matrix for treating a serious limb-threatening wound in a 33-year-old male with a right lower limb injury. After treatment, the wound was fully closed, tissue granulation was grown, skin grafting was done, and the right leg was saved. In conclusion, the combination of the mentioned components can be utilized to synergistically enhance wound healing and preserve the limb.

Autologous platelet-rich-plasma injection and platelet-rich fibrin glue interposition for treatment of anal fistula resistant to surgery.

Aim: The current study purposed to evaluate the autologous platelet-rich plasma (PRP), and platelet-rich fibrin glue (PRFG) effect on the treatment of complex, and recalcitrant anal fistula (AF) which was not cured by several surgeries. Background: AF has remained one of difficult challenges for centuries. Surgery is the common treatment method for it, but the risk of fecal incontinence and recurrence is still a distressing complication for patients and surgeons. New procedures were published in the scientific literature, each with advantages and disadvantages. According to reports, an effective therapy option is the autologous fibrin glue that is rich in platelets. Methods: Autologous PRP and PRFG were prepared from 10 patients' own blood. The surgeon curetted the tract of anal fistula for the deepithelialisation till hemorrhage occurred; PRP was injected around the fistula into the tissue, and PRFG was interpositioned in the tract. Age, number of previous surgeries, complications, number of PRP and PRFG administrations, and duration of halting the discharge were among the information gathered. Patients were followed up between 10 months to 84 months after treatment. Results: No complications were observed during and after the injection. During the period of follow-up, AF leakage was stopped for 6 patients, but not for 4 patients. Conclusion: Since autologous PRP injection, and PRFG interposition is a safe, effective, and minimally invasive procedure for resistant AF to surgeries; it can be used, along with surgery to increase the healing rate of complex anal fistula.

Fenugreek Seed Extract Regulates Human Umbilical Vein Endothelial Cell Angiogenesis and Proliferation via the PI3K/Akt/Cyclin D1 Pathway.

The significance of angiogenesis in tumour progression has been widely documented. Hence, the identification of anti-angiogenic agents with fewer common side effects would be valuable in cancer therapy. In this study, we evaluated the anti-angiogenic and anti-proliferative effects of a hydro-alcoholic extract of fenugreek seed (HAEF) on human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cells were treated with various concentrations of HAEF and the half-maximal inhibitory concentration (IC50) value was estimated by using the MTT assay. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase enzyme (MMP-2 and MMP-9) gene expression profiles were evaluated by using quantitative RT-PCR (qRT-PCR). Moreover, MMP activities and PI3K, Akt and cyclin D1 protein expression levels were evaluated by gel zymography and Western blotting, respectively. HAEF reduced HUVEC viability, with an IC50 value of 200 µg/ml. The qRT-PCR results demonstrated that treatment with HAEF markedly reduced MMP-2/MMP-9, VEGF and bFGF gene expression, as compared to the control group. We also found that MMP-2/MMP-9 enzyme activity and PI3K/Akt/cyclin D1 protein expression were notably decreased in cells treated with HAEF. Our results suggest that HAEF can potentially inhibit angiogenesis, and also affect cellular proliferation by targeting the PI3K/Akt/cyclin D1 pathway. Thus, fenugreek seed extract merits further investigation as a source of compounds with anti-cancer properties.

Autologous Platelet-Rich Plasma Injection and Platelet-Rich Fibrin Glue Insertion for the Treatment of Extensive Supralevator Anorectal Fistula: A Case Report.

Supralevator fistula stays a challenge in general surgery. We present a case with supralevator anorectal fistula and subsequent retroperitoneal necrotizing fasciitis in which autologous platelet-rich plasma and platelet-rich fibrin glue were used for fistula closure. A 59-year-old man was admitted with pelvic pain and fever. Abdominopelvic sonography and CT scan reported a deep horseshoe-shaped anorectal abscess with extension to the pelvic floor, supralevator, psoas, retroperitoneal muscles, and kidneys. He was managed with antibiotics, abscess drainage, repeated radical surgical debridement, and necrosectomy. After 30 days, he was discharged, but he returned to the office with the complaint of purulent discharge from the hypogastric region and a diagnosis of fistula formation. Platelet-rich plasma was injected around the fistula into the tissue, and platelet-rich fibrin glue was introduced to the fistula tract. At the 11-month follow-up, the patient did not have voiding dysfunction, constipation, diarrhea, or fistula tract infection. Autologous platelet-rich plasma injection and platelet-rich fibrin glue insertion suggest a secure and effective approach for treating supralevator anorectal fistula.

PRP-Fibrin Glue for Pain Reduction and Rapid Healing in Tonsillectomy.

Introduction: Many ongoing challenges have been applied to reduce the considerable postoperative pain and increase wound healing after tonsillectomy, but they are still not optimally managed. This study applied autologous platelet-rich plasma (PRP) & platelet-rich fibrin glue (PRFG) to reduce pain and increase wound healing. Materials and Methods: PRP & PRFG were prepared from 26 patients' blood. At the end of the tonsillectomy, one tonsillar bed was selected randomly, PRP was injected, PRFG was applied topically on the bed wound, and the other sites were left untreated. The treated and untreated tonsillar beds were compared for pain and wound healing the next day, 3rd day, 6th day, 9th day, and 15th day. Results: There were no complications during and after the injection. The mean age was 24.76 ±5.54 years. In the treated beds in comparison to untreated beds, pain decreased marginally in 1st day (intervention:4.5±2.54, control:5.53±2.94, P-value=0.18) and 3rd day (intervention:3.92±2.96, control:4.8±2.82, P-value=0.276), and significantly in 6th day (intervention:2.3±2.46, control:3.92±2.6, P-value=0.026), 9th day (intervention:1.26±1.48, control:2.76±2.4, P-value=0.009) and 15th day (intervention:0.73±1.07, control:1.84±2.36, P-value=0.08) after surgery. Healing did not change in 1st day (P-value=1), changed marginally in 3rd day (P-value=0.2), and increased significantly in 6th day (P-value=0.001), 9th day (P-value=0.006), and 15th day (P-value=0.004) after surgery. Conclusions: Autologous PRP injection & PRFG application offer an effective, safe, and non-invasive method for reducing pain and increasing wound healing after tonsillectomy.

Comparative Analysis of the Effectiveness of Intra-Articular Injection of Platelet-Rich Plasma versus Hyaluronic Acid for Knee Osteoarthritis: Results of an Open-Label Trial.

BACKGROUND: Platelet-rich plasma (PRP), an autologous source of growth factors, and hyaluronic acid (HA) are among the minimally invasive treatments for knee osteoarthritis (OA). This trial was designed to compare the effectiveness of intra-articular injection of PRP with HA (as one of the standard treatments) on mild to moderate knee OA. METHODS: In this phase I open-label clinical trial, 10 patients underwent intra-articular PRP injection and 10 others received HA injection. At baseline (pre-injection) visit and 1, 3, 6, and 12 months post-injection, clinical assessments were performed using visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Physical examinations of the knee, including crepitation and range of motion (ROM) were performed at each visit. The follow-up responses were compared with the baseline visit. RESULTS: The PRP treatment was ascertained to be safe and caused no adverse effects. Significant improvements in the majority of KOOS subscales and VAS were found throughout the entire 12-month follow-up, following the PRP injections. HA injection, however, caused only one month significant improvement in the majority of patient-reported outcomes. In the majority of visits, the extent of improvements in the scores of KOOS subscales, as well as the extent of reduction in VAS were significantly greater in PRP recipients, compared to HA recipients. The ROM in both groups slightly increased after interventions. The frequency of coarse crepitation, which was detected in 100% of the patients in both groups at the baseline visit, decreased significantly to fine crepitation at the first follow-up visit in 80% and 40% of the PRP and HA recipients, respectively. CONCLUSION: Intra-articular injection of PRP or HA alleviates symptoms and pain and improves functionality and physical examinations in patients with knee OA. However, PRP therapy produces greater and longer-lasting improvements in most of the outcome parameters compared to HA.

Methylene blue for treatment of hospitalized Covid-19 patients: a randomized, controlled, open-label clinical trial, phase 2

ABSTRACT Background: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients. Objective: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR). Methods: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days. Results: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p < 0.0001) and also the 5th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively. Conclusions: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288

METHYLENE BLUE FOR TREATMENT OF HOSPITALIZED COVID-19 PATIENTS: A RANDOMIZED, CONTROLLED, OPEN-LABEL CLINICAL TRIAL, PHASE 2.

BACKGROUND: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients. OBJECTIVE: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR). METHODS: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days. RESULTS: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p < 0.0001) and also the 5th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively. CONCLUSIONS: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288.

Platelet-rich Plasma use for facial rejuvenation: a clinical trial and review of current literature.

BACKGROUND AND AIM OF THE WORK: Several studies have shown beneficial effects for Platelet-rich plasma (PRP). We aimed to assess the efficacy of pure PRP injection for facial rejuvenation in Iran. METHODS: 30 female consecutive participants were injected with PRP in two sessions with 3 month interval. Evaluations were performed by comparing the pre- and post-improvement measurements of skin scan, before after photography by participants, therapeutic physician and blindly by a second dermatologist. RESULTS: In 3 and 6 months follow-ups respectively,  moderate to excellent improvement in periorbital dark circles (47.8,60.9%), periorbital wrinkles (73.9%,78.3%), nasolabial fold (52.2%,56.6%) and skin rigidity (52.3%,60.9%)  reported by patients, was statistically significant only for dark circle(P value 0.031). Moderate to good improvement in periorbital dark circles (47.9%,74%), periorbital wrinkles (39.1%,43.5%)and nasolabial folds (4.3% ,13.1%)  demonstrated by therapeutic physician's evaluation , was statistically significant for dark circle (P value 0.008) and nasolabial folds (P value 0.025). Moderate to good improvement in periorbital dark circles (34.8%, 52.2%), periorbital wrinkles (26.1%, 34.8%) and nasolabial folds (4.4%, 13%)   by second dermatologist, was statistically significant for dark circle (P value 0.025). CONCLUSION: Face rejuvenation with PRP is a promising and noninvasive technique with best results observed in improving periorbital dark circles and wrinkles.

The effect of platelet-rich plasma-fibrin glue dressing in combination with oral vitamin E and C for treatment of non-healing diabetic foot ulcers: a randomized, double-blind, parallel-group, clinical trial.

OBJECTIVE: The current study assesses the effects of platelet-rich plasma-fibrin glue (PRP-FG) dressing along with oral vitamin E and C on wound healing and biochemical markers in patients with non-healing diabetic foot ulcers (non-healing DFU). METHODS: This randomized controlled trial was performed on 25 patients with non-healing DFU. Patients were treated with PRP-FG dressing plus oral vitamin E and C (intervention group) or PRP-FG dressing plus placebo (control group) for 8 weeks. RESULTS: Eight weeks after treatment, six wounds in the intervention group and two wounds in the control group were completely closed, and also wound size significantly reduced in both intervention and control groups (p < 0.05). This reduction in wound size was significantly greater in the intervention group compared to the control group (p = 0.019). Also, a significant decrease in prooxidant-antioxidant balance (PAB) , ESR, and hs-CRP was observed in the intervention group compared to the control group (p < 0.05). CONCLUSION: Our results showed that PRP-FG dressing along with oral vitamin E and C could be used to increase wound healing in patients with non-healing DFU by enhancing the wound healing process and reducing oxidative stress. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04315909).

Platelet-rich plasma fibrin glue for treatment of chylothorax following cavopulmonary connections.

OBJECTIVES: The postoperative persistence of chylothorax is a fatal complication of paediatric cardiac surgery. There is an urgent need for an effective treatment of chylothorax. This study reports the application of allogenic platelet-rich plasma fibrin glue (PRP-FG) as a conservative therapy before reoperation. METHODS: Over a 9-year period, from 2010 to 2019, 27 patients with persistent chylothorax following a cavopulmonary connection, with a mean latency period of 11 days (range 10-15 days), were treated with PRP-FG. These patients were selected because they had not responded positively to initial conservative management plans. The patients were followed up for 9 years. RESULTS: Twenty-five patients (92%) responded positively to treatment with PRP-FG; 2 patients did not respond to the treatment and died after reoperation. All of the successfully treated patients in follow-up continued to live a healthy life without further complications. CONCLUSIONS: Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates.

The Application of a Reduced Dye Used in Orthopedics as a Novel Treatment against Coronavirus (COVID-19): A Suggested Therapeutic Protocol.

The severe acute respiratory syndrome caused by COVID-19 is now a global catastrophic event. Currently there is no approved drug or vaccine for the disease. Methylene blue (MB, oxidized form, blue color) has been used in many different areas of clinical medicine, ranging from malaria to orthopedics. Leucomethylene Blue (reduced form of MB, colorless) may be applied for the treatment of COVID-19 according to the scientific evidences. In severe patients, there is a cytokine storm (hyperinflammation) and high oxidative stress (OS). Inflammation and OS has a mutual correlation and exacerbate each other. In human body, MB first induces OS through absorbing electron (like a free radical) from other molecules, if the body could counteract to this OS, then reduced MB decreases OS through other mechanisms. Reduced MB could prevent inflammation, propagation of the virus RNA, and also improves hypoxia through reducing methemoglobin. Therefore, to avoid the increment of OS, we suggest using Leucomethylene Blue through the following protocol: The IV cocktail contains 50 mg MB (1mg/kg, 50-kg weight), 1000-2000 mg vitamin C, 500-1000 mg N-Acetylcysteine (or glutathione or cysteine or α-lipoic acid) and 10-20 gr urea (optional) in 100 ml dextrose 5%. Before the injection, the cocktail should be kept in a dark place for 1-2 hour to become fade or colorless.

The effect of platelet-rich plasma injection in the treatment of androgenetic alopecia.

BACKGROUND: Androgenetic alopecia is the most common type of hair loss in men, which is manifested by a progressive terminal hair loss in specific areas of scalp. Platelet-rich plasma (PRP) is among treatment options for androgenetic alopecia. PRP is a human platelet concentrate in a small volume of plasma containing certain cytokines. AIM: The aim of this study was to evaluate the efficacy and safety of autologous PRP in treatment of male androgenetic alopecia. METHODS: This was a clinical trial in 19 patients with grade III vertex to grade V androgenetic alopecia referring to the Clinic of Ghaem Hospital between March 2015 and March 2016. All obtained liquid PRP (5 cc) was injected at around 125 points (equals to 125 cm2 ) into the scalp, and operation was repeated in three sessions at 0, 4, and 8 weeks. We took macroscopic and dermoscopic pictures of each patient in 0, 4, and 8 weeks and 3 months after the last injection session. A dermatologist evaluated the treatment response using dermoscopy photos. RESULT: Our results showed that the trend of hair thickness and number variations during study period was significant (P < 0.001). However, there was no significant change in the hair thickness from the second injection forward. Our findings indicate the number of hair follicles during follow-up in pairwise comparison was significantly more than baseline. CONCLUSION: Findings of our study were in line with other studies in this field and showed that the use of PRP as a new and safe treatment can be effective in androgenetic alopecia.

Prooxidant-antioxidant balance in Iranian veterans exposed to mustard gas and its correlation with biochemical and hematological parameters.

The present study aimed to evaluate serum prooxidant -antioxidant balance (PAB) in an Iranian population exposed to sulfur mustard (SM) more than 20 years ago. In this study, 42 SM-exposed subjects and 30 unexposed subjects (as controls) were recruited. Serum PAB, biochemical, and hematological parameters were measured in all subjects. Correlation of PAB with biochemical and hematological parameters was determined. The mean PAB values in the SM-exposed group (82.5 ± 34.8 HK) were significantly higher than that in the control group [47.5 ± 17.8 HK] (p < 0.001). The results demonstrated that serum PAB values were positively correlated with alkaline phosphatase activities in the SM-exposed group. Furthermore, PAB values showed a significant negative correlation with hepatic enzymes (AST, ALT), triglycerides, total bilirubin, and mean corpuscular hemoglobin concentrations. PAB values showed a borderline significant negative correlation with uric acid. The present results suggest that late oxidative stress and alterations in biochemical and hematological parameters may be a consequence of the frequent respiratory infections rather than direct toxic effects of SM.

Determining Pro-Oxidant Antioxidant Balance (PAB) and Total Antioxidant Capacity (TAC) in Patients with Schizophrenia.

Objective: Schizophrenia is a disease with unknown etiology. There is evidence suggesting that oxidative damage occurs in schizophrenia. Oxidative damage may arouse from imbalance between oxidant and anti-oxidant factors in cellular and tissue environment. Although it may not be the primary cause, it can worsen the disease and may be a reason of poor response to therapy in these patients. The present study aimed at evaluating the pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) in serum of schizophrenia patients. PAB is an assay to determine the pro-oxidant load and antioxidant capacity in a single measurement. Method : In this cross- sectional study, patients with diagnosis of schizophrenia, who referred to a psychiatry university hospital (Ibn-e-Sina Hospital) affiliated to Mashhad University of Medical Sciences, were enrolled. Patients' demographic characteristics and laboratory data were recorded from patients' files. Serum PAB and TAC were measured using a special PAB assay and commercial kit, respectively. Data were analyzed using SPSS 16. Results: A total of 84 individuals (42 schizophrenia cases and 42 healthy controls) participated in this study. Controls were age and sex-matched with the patients' group. The mean TAC in the patient and control groups was 0.49±0.04 and 0.51±0.04 nmol/L, respectively (p = 0.16). PAB was higher in patients' group than in controls (127.36±36.44 vs. 118.93±52.34 HK), however, this difference was not statistically significant (p = 0.09). The change was correlated with the chronicity of the disease. Conclusion: Pro-oxidant antioxidant balance was elevated in serum of patients with schizophrenia. These data suggested the occurrence of oxidative stress during the progression of the disease. Lower antioxidant capacity might suggest that patients with schizophrenia could be more susceptible to oxidative stress damage.

The Status of Nitric Oxide and its Backup, Heme Oxygenase 1, in Thromboangiitis Obliterans.

BACKGROUND: Until recently, a gene polymorphism in the promoter region of endothelial nitric oxide synthase has been suggested as a risk factor for thromboangiitis obliterans (TAO) development. The aim of this study was to compare the metabolites of nitric oxide (NO) and its backup, heme-oxygenase-1 (HMOX1), between TAO patients and those of a smoking control group matched by race, age, sex, and smoking habits. METHODS: Twenty-four male Caucasian TAO patients and 20 male Caucasian controls enrolled in the study. Their smoking habits were matched based on the serum cotinine levels of 17 of the TAO patients and the 20 controls. A colorimetric kit was used to measure NO, and an enzyme-linked immunosorbent assay kit was used to measure cotinine and HMOX1 levels. RESULTS: The mean serum level of NO metabolites in the TAO group was significantly less than in the controls (p = 0.03) and also significantly less in the patients with below-knee amputations than in non-amputees (p= 0.018). Also, HMOX1 was significantly greater in the TAO patients than in the controls (p= 0.01). No significant correlation was found between NO and HMOX1 (p = 0.054). CONCLUSION: Nitric oxide may play a pivotal role in TAO development and its outcome. However, the intact HMOX1 pathway may demonstrate the unique role of NO, which cannot be compensated for by HMOX1 and whose absence may make patients susceptible to developing TAO. In addition, another pathway besides NO, with influence on vascular tone and hemostasis, might be involved in TAO development, such as the autonomic nervous system. Further studies are suggested regarding these issues.