Side chain inset of neurogenerative amino acids to metalloproteins: a therapeutic signature for huntingtin protein in Huntington's disease.

OBJECTIVE: Huntington's disease is a dominant autosomal inherited neurodegenerative disease that results in progressive impairment, characterized by dementia, chorea, and behavioral and cognitive decline. The objective of this study was to investigate the potential activity of metalloproteins against the huntingtin protein using various insertion-based engineering computational methods. Metalloproteins, metal protein complexes involved in important biochemical and physiological processes, were explored as potential drug candidates for Huntington's disease. MATERIALS AND METHODS: A total of 18 metalloproteins were selected as drug candidates and studied to assess their potential inhibitory effects on the huntingtin protein. The screening process was based on the lowest binding energy. The metalloprotein with the lowest docking score was chosen for side chain insertion of neurogenerative amino acids. The engineered metalloprotein was then evaluated based on physiochemical properties, allergenicity, toxicity, and surface accessibility. Cloning and expression analysis was performed to further investigate its potential as a therapeutic agent. RESULTS: The metalloprotein chosen for side chain insertion, cytochrome C oxidase, showed promising results. It was computed as a probable non-allergen and exhibited no toxic domains, indicating its non-toxic nature. Additionally, it demonstrated a strong binding affinity with the huntingtin protein, with a binding energy of -1,253.3 Kcal/mol. CONCLUSIONS: Metal-based proteins, when engineered with additional neurogenerative amino acids, hold potential as drug candidates for treating neurodegenerative diseases such as Huntington's disease. The successful development of these engineered metalloproteins could offer therapeutic advantages. Further testing, both in vitro and in vivo, is necessary to evaluate their efficacy and validate their potential activity as novel drugs for the treatment of neurodegenerative diseases.

Iron Protein Succinylate in the Management of Iron Deficiency Anemia: A Comparative Study with Ferrous Sulphate at Low and High Therapeutic Doses.

Oral iron supplementation constitutes the first line treatment for iron deficiency anemia (IDA), with daily doses between 80 mg and 200 mg of elemental iron. Ferrous salts, such as ferrous sulphate (FeSO4), while efficacious, frequently give rise to gastrointestinal side effects. In the present paper we attempted to directly compare the efficacy of an alternative to the FeSO4 formulation, which presents a better tolerability profile, iron protein succinylate (Ferplex®). In a diet-induced anemia model, rats were treated by oral gavage with vehicle, FeSO4, or Ferplex® at a human-dose equivalent of 80 mg and 200 mg of elemental iron. We evaluated the change in anemia-related hematological and biochemical parameters, conducting a histological examination of the intestine at sacrifice. Results indicate that both types of iron supplementation are equally effective in the treatment of IDA, restoring hemoglobin, hematocrit, erythrocytes, free iron and transferrin levels in 15 days, with no statistical differences between treated groups and control. The impact of anemia on body weight was also attenuated following treatment with both iron supplements. Thrombocyte and reticulocyte levels, altered by the anemic condition, returned to homeostasis after 15 days of either FeSO4 or Ferplex® treatment. Importantly, the lower and higher doses of iron were equally effective, thus supporting the current school of thought which states that lower therapeutic doses are sufficient for management of IDA. In addition, the study shows for the first time that oral treatment with Ferplex® does not increase serum hepcidin. Finally, Ferplex® induced minimal iron depositions in the intestinal tissue compared to FeSO4.

Efficacy and tolerability of oral iron protein succinylate: a systematic review of three decades of research.

Objective: Oral supplementation with iron is a standard intervention for treating or preventing iron deficiency with or without anemia. Over the last few decades, various forms of oral iron have been developed to improve treatment tolerability and iron bioavailability. In this review, we gathered research data regarding the use of iron protein succinylate since it was first marketed in the 1980s.Methods: Electronic databases - PubMed and the Cochrane Library - were searched for studies published up to March 2019. Clinical or observational studies reporting data on the tolerability of oral iron protein succinylate were included. Results were statistically described to evaluate and compare the efficacy and safety of iron protein succinylate with the comparators under study.Results: Iron protein succinylate was investigated in 54 studies: 38 randomized clinical trials and 16 observational studies, with a total of 8454 subjects. Of them, 8142 were included in the efficacy analysis: patients were divided into three population subtypes: general (n = 1899), gynecological/obstetric (n = 5283), and pediatric (n = 960). In total, 6450 patients received iron protein succinylate, experiencing a significant change in hemoglobin and ferritin in all populations. The change in all parameters was similar or higher with iron protein succinylate compared to other iron treatments evaluated. Overall, study groups receiving iron protein succinylate reported the lowest rate of adverse events.Conclusions: Although all iron treatments analyzed are effective and safe, our results suggest that iron protein succinylate may be an excellent choice to treat iron deficiency and anemia due to its superior effectiveness and tolerability.

Native nanodiscs from blood inhibit pulmonary fibrosis.

Blood is a treasure trove whose constituents have attracted increasing attention for use in understanding and controlling disease. However, the functions of blood, especially with regard to its composition at the nanoscale, remain largely unknown. Inspired by exosomes and lipoproteins, the present work isolated and characterized biotic nanodiscs from human blood (BNHBs) using multiple techniques. The isolated BNHBs had diameters of 10-30 nm and a thicknesses of approximately 2.9 nm. The BNHB concentration in blood peaked at 34.5 ±â€¯5.19 mg/mL (20-fold higher than that of high-density lipoproteins and exosomes). BNHBs had high biocompatibility, facile cell internalization and strong biological control of pulmonary fibrosis. The BNHBs were hybrids of many metalloproteins and metabolites and contained a few functional proteins similar to lipoproteins or exosomal proteins. BNHBs inhibited transforming growth factor-beta 1 (TGF-ß1)-induced fibrosis damage in human embryonic lung fibroblasts (HELFs) by inhibiting the expression of α-smooth muscle actin and collagen-1 protein. BNHBs also intensively bound TGF-ß1 to inhibit TGF-ß1 activity in fibrogenesis. BNHBs successfully reduced pulmonary inflammation and collagen deposition in a mouse model, preventing pulmonary fibrosis. Applying the protective properties of nanodiscs may be a novel therapeutic approach for pulmonary and other diseases.

Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury.

BACKGROUND: The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation therapy (RT) mitigates development of pulmonary toxicity in rats. METHODS: Female F344 rats (n = 60) were divided among six experimental groups: (1) RT, single dose of 21 Gy to the right hemithorax; (2) RT + 5 mg/kg bSOD; (3) RT + 15 mg/kg bSOD; (4) No RT; (5) sham RT + 5 mg/kg bSOD; and (6) sham RT + 15 mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 h post-radiation. The effects of bSOD on radiation-induced lung injury were assessed by measurement of body weight, breathing frequency, and histopathological changes. Immunohistochemistry was used to evaluate oxidative stress (8-OHdG(+), NOX4(+), nitrotyrosine(+), and 4HNE(+) cells), macrophage activation (ED1(+)), and expression of profibrotic transforming growth factor-ß or TGF-ß in irradiated tissue. RESULTS: Radiation led to an increase in all the evaluated parameters. Treatment with 15 mg/kg bSOD significantly decreased levels of all the evaluated parameters including tissue damage and breathing frequency starting 6 weeks post-radiation. Animals treated with 5 mg/kg bSOD trended toward a suppression of radiation-induced lung damage but did not reach statistical significance. CONCLUSIONS: The single application of bSOD (15 mg/kg) ameliorates radiation-induced lung injury through suppression of reactive oxygen species/reactive nitrogen species or ROS/RNS-dependent tissue damage.

[Clinical study of iron protein succinylate oral solution for preventing and treating anemia of prematurity].

OBJECTIVE: To evaluate the efficacy and safety of iron protein succinylate (IPS) oral solution in preventing and treating anemia of prematurity (AOP). METHODS: Sixty premature infants less than 35 weeks of gestation were randomly divided into IPS (n=30) and polysaccharide iron complex (PIC) groups(n=30). Treatment began at two weeks after birth. The infants received IPS or PIC in addition to recombinant human erythropoietin. On days 14, 28, 42, and 60 after treatment, hemoglobin (Hb), red blood cell count(RBC), hematocrit (HCT), percentage of reticulocytes, serum iron, and serum ferritin were determined. Liver and renal functions were evaluated before and after treatment. RESULTS: There were significant differences in the changing trends of RBC and HCT between the two groups (P<0.05). In the IPS group, RBC and HCT gradually decreased after birth, but began to rise gradually on days 28 and 42 of treatment; in the PIC group, RBC and HCT kept decreasing from birth to day 60 of treatment. On day 60 of treatment, the IPS group had significantly higher levels of Hb, RBC, HCT, serum iron, and serum ferritin than the PIC group (P<0.05). No notable adverse events occurred in either group. CONCLUSIONS: IPS oral solution has good efficacy and tolerability in preventing and treating AOP.

Iron complex, dabigatran and toxic epidermal necrolysis syndrome: a case-report.

WHAT IS KNOWN AND OBJECTIVE: Toxic Epidermal Necrolysis Syndrome falls in the spectrum of acute idiosyncratic bullous disorders with medications being the major aetiological factor. The authors review the relevant literature and report a case of Toxic Epidermal Necrolysis Syndrome where two medications, iron protein succinylate and dabigatran, not previously associated with the disorder might have acted as precipitants to it. CASE SUMMARY: An 86-year-old female recently introduced to iron protein succinylate and dabigatran, presented with a widespread rash consisting of erythematous macules symmetrically distributed on her torso and both upper and lower limbs, down to her extremities. She was diagnosed with Toxic Epidermal Necrolysis Syndrome. None of the drugs previously implicated with the disorder were listed in her recent prescriptions. It was therefore concluded that the two most recently initiated medications, iron protein succinylate and dabigatran, might have been the cause. They were both discontinued to good effect for our patient. WHAT IS NEW AND CONCLUSION: Although neither iron protein succinylate nor dabigatran has been incriminated as causative of Toxic Epidermal Necrolysis Syndrome, we believe that either one of these or their interaction might have acted as the precipitant to this condition. We suggest that the possibilities of the above associations should be further explored.

Medical management of Peyronie's disease.

Peyronie's disease (PD) is a wound-healing disorder in which a fibrotic plaque forms in the tunica albuginea layer of the penis. It clinically presents as any combination of penile pain, angulation, and erectile dysfunction. Recent studies indicate that PD has a prevalence of 3%-9% in adult men. Although the exact etiology has not been established, PD likely results from a predisposing genetic susceptibility combined with an inciting event such as microtrauma during intercourse. During the initial acute phase (6-18 months), the condition may progress, stabilize, or regress. For this reason authorities recommend a more conservative treatment approach, with a trial of oral and/or intralesional pharmacotherapy, before surgical reconstruction is considered. Oral therapies most commonly employed include tocopherol (vitamin E) and paraaminobenzoate (Potaba), with colchicine, tamoxifen, propoleum, and acetyl-L-carnitine being used less often. There are a limited number of long-term placebo-controlled studies with these oral agents, and for the most part, studies have failed to show a consistent beneficial effect. Intralesional injection therapy for PD is more commonly used as a first-line therapy. The current standard of care includes injection with interferon-alpha-2b, verapamil, or collagenase. Interferon-alpha-2b, in particular, has been documented in a large, multicenter, placebo-controlled study to show significant benefit over placebo in decreasing penile curvature, plaque size, penile pain, and plaque density. However, intralesional interferon is associated with posttreatment flu-like symptoms unless patients are premedicated with a nonsteroid anti-inflammatory agent. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids, orgotein, radiation, and extracorporeal shockwave therapy. Surgery is considered when men with PD do not respond to conservative or medical therapy for approximately 1 year and cannot perform satisfactory sexual intercourse. Ongoing basic research in PD will likely identify future targets for medical exploitation.

Chlorhexidine and preservation of sound tooth structure in older adults. A placebo-controlled trial.

The Trial to Enhance Elderly Teeth Health (TEETH) was designed to test the impact of regular rinsing with a 0.12% chlorhexidine (CHX) solution on tooth loss, and the causes of tooth loss (caries, periodontal disease and trauma) were also investigated. This paper reports on the effectiveness of a 0.12% CHX solution for controlling caries using a tooth surface (coronal and root) survival analysis. A total of 1,101 low income elders in Seattle (United States) and Vancouver (Canada), aged 60-75 years, were recruited for a double-blind clinical trial and assigned to either a CHX (n = 550) or a placebo (n = 551) mouth rinse. Subjects alternated between daily rinsing for 1 month, followed by weekly rinsing for 5 months. All sound coronal and root surfaces at baseline were followed annually for up to 5 years. At each follow-up examination, those tooth surfaces with caries, restored, or extracted were scored as 'carious'. The hazard ratio associated with CHX for a sound surface to become filled, decayed, or extracted was 0.87 for coronal surfaces (95% confidence interval: 0.71-1.14, p = 0.20) and 0.91 for root surfaces (95% confidence interval: 0.73-1.14, p = 0.41). These findings suggest that regular rinsing with CHX does not have a substantial effect on the preservation of sound tooth structure in older adults.

Anti-inflammatory agents in the management of alimentary mucositis.

BACKGROUND: Alimentary mucositis is a significant complication of cancer therapy, with important clinical and economic implications. MATERIALS AND METHODS: In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology conducted an evidence-based review of the literature on alimentary mucositis. The goal of this literature review was to update previously published guidelines for the management of mucositis. RESULTS: This article reports the findings of the subgroup charged with reviewing the literature related to anti-inflammatory interventions. Considerable preclinical and clinical evidence suggests that the use of anti-inflammatory agents may be a promising approach to reduce the severity of mucositis. However, there was not enough evidence to support any new guidelines advocating the use of any specific anti-inflammatory intervention. CONCLUSION: Thus, there is a need for well-designed clinical trials evaluating the use of anti-inflammatory agents in the management of mucositis.

Efficacy of orgotein in prevention of late side effects of pelvic irradiation: a randomized study.

PURPOSE: To study whether orgotein is effective in preventing late radiation-induced effects. METHODS AND MATERIALS: Patients >18 years old who were diagnosed with rectal cancer, had an indication for pelvic irradiation (RT) after surgery, and complied with the selection criteria were randomly assigned at the end of RT to receive orgotein for 7 weeks or no treatment (control). The Radiation Therapy Oncology Group toxicity scale was used to evaluate the RT-induced side effects for up to 2 years. Interruptions due to toxicity, concomitant medication, and non-RT adverse events were also recorded. RESULTS: A total of 100 patients were included, with 50 in each group. The groups were comparable in terms of the demographic and baseline characteristics. The orgotein group had statistically significant less late toxicity than the control group (p = 0.036) and nontreated patients had a 66% greater chance of developing late toxicity at 2 years. Grouping toxicity as nonrelevant (Radiation Therapy Oncology Group Grade 0-1) and relevant (Grade 2 or worse), patients given orgotein had a lower incidence of late relevant toxicity than did controls, with statistical significance reached at all follow-up visits. After 2 years, patients not treated with orgotein had, in general, a 37% greater chance of developing late relevant toxicity; this risk was 26% when referring specifically to GI toxicity. No adverse events attributable to orgotein were recorded at any time during the study. CONCLUSION: Orgotein is a safe treatment that significantly prevents the overall occurrence of late toxicity, with toxicity reduction particularly evident in the lower GI tract.

[Xinxibao for the treatment of chronic bacterial prostatitis].

OBJECTIVE: To study the effect of Xinxibao as a supplementary drug in the treatment of chronic bacterial prostatitis (CBP). METHODS: Eighty-one cases of CBP were divided into two groups: Group A (n = 38), treated with Xinxibao combined with sensitive antibiotic, and Group B (n = 43), treated with sensitive antibiotic only. Contrast studies were made on the therapeutic effects in the two groups, and the results were analyzed. RESULTS: The effectivity rate was significantly higher in Group A than in Group B. CONCLUSION: Xinxibao can effectively relieve the symptoms of CBP.

The efficacy of orgotein in the treatment of acute toxicity due to radiotherapy on head and neck tumors.

AIMS AND BACKGROUND: To assess the efficacy of orgotein in the treatment of acute secondary effects of radiotherapy on head and neck tumors. MATERIAL AND METHODS: Data were collected on 41 patients who received radiotherapy for tumors of the head and neck. Radiotherapy was the exclusive treatment in 19.5% of cases, with surgery in 24.4%, chemotherapy in 48.8%, and with both in 7.3%. The toxicity requiring use of orgotein was: oropharynx mucositis (26.8%), dysphagia (34.2%), or both (39%), in grade 2 or more according to the RTOG scale. Orgotein (8 mg i.m.) was administered every 48 hrs until radiotherapy was finished. RESULTS: The overall response rate was 92.5%; a complete response was obtained in 12 patients (30%) and partial in 25 (62.5%). The reduction in toxicity at the end of radiotherapy was one grade in 18 patients (45%), 2 grades in 16 (40%), 3 in 2 patients (5%), and 4 grades in the only patient with grade 4 acute toxicity. A statistically significant influence was shown in obtaining complete response: laryngeal tumor location (P = 0.037), duration of radiotherapy of more than 53 days (P = 0.002), discontinuation for non-toxic reasons (P = 0.008). CONCLUSIONS: We consider that orgotein is highly effective in dealing with acute secondary effects of radiotherapy on the head and neck area.

Aerosol orgotein (Ontosein) for the prevention of radiotherapy-induced adverse effects in head and neck cancer patients: a feasibility study.

Orgotein is an anti-inflammatory superoxide dismutase agent successfully used in treating several inflammatory diseases. It is also used in treating radiation-induced adverse effects in difference malignancies, notably breast, lung, bladder, prostate, cervix, and head and neck cancers. It is administered either topically or parenterally. To our knowledge, it has never been used before for prophylaxis of radiation-induced adverse effects or in aerosol form. Here we report on the results from a feasibility study on aerosol orgotein (Ontosein) for prevention of acute and deferred radiation-induced adverse effects in patients treated for head and neck malignancies. Our results show that aerosol orgotein administered before each radiation therapy session may impart some benefits in both incidence and severity of acute and deferred radiation-induced adverse effects in head and neck cancer patients, when compared with historical controls. In addition, aerosol orgotein administration is easy and convenient for both the patient and the radiotherapist.

Transdermal electromotive multi-drug administration for Peyronie's disease: preliminary results.

The purpose of this study was to clarify the actual therapeutic potential of a new transdermal drug delivery system (electromotive drug administration; EMDA) for selected patients with Peyronie's disease. Forty patients with Peyronie's disease were treated by electromotive administration of the 3-drug association orgotein-dexamethasone-lidocaine in a double-blind, placebo-controlled, partial crossover study (study 1). Another 25 patients were treated by EMDA with a combination of verapamil-dexamethasone in an uncontrolled study (study 2). Treatment sessions lasted 20 minutes each and took place 3 times a week for 3 weeks with a current of 3 mA. Patients were assessed before treatment and at 1- and 3-month follow-up examinations. Assessments were based on sexual history, physical examination, and dynamic color Doppler ultrasonographic results. Adverse effects of EMDA were not reported. In study 1, the clinical results observed after treatment proved to be significantly better than those of the placebo. Penile pain disappeared in all patients in both studies. Penile lesion (nodule or plaque) either disappeared or significantly improved in 79% and 90% of patients treated by the 3- and 2-drug association, respectively. The improvement of penile deformity also was notable although it did not match the effect observed on penile nodules or plaque (62% and 88%, in studies 1 and 2, respectively). In both studies, more than 80% of patients reported a definite amelioration of penile rigidity, which paralleled the improvement of penile dynamic color Doppler ultrasonographic parameters. Overall, the combination of verapamil-dexamethasone achieved better clinical results than the 3-drug combination. Electromotive drug administration is a novel technique capable of safely achieving satisfactory results in selected patients with Peyronie's disease not only in terms of improvement of patient's symptoms but also due to the reduced need for penile surgery.

Comparative study of tolerability and efficacy of iron protein succinylate versus iron hydroxide polymaltose complex in the treatment of iron deficiency in children.

One-hundred children, 48 males and 52 females, mean age +/- SD 39.9 +/- 28.2 months (range 12 to 113) with sideropenia or sideropenic anemia were randomly divided into 2 groups of 50 patients each (groups A and B) and were treated with iron protein succinylate (group A) or iron hydroxide polymaltose complex (group B). Patients of both groups received 4 mg/kg elemental iron, maximally 80 mg daily, for 2 months. Side-effects of therapy and laboratory values (RBC, hematocrit, hemoglobin, MCV, serum iron, total iron binding capacity, and ferritin) were registered before treatment, 30 days after the beginning of therapy as well as after 60 days in order to evaluate tolerability and efficacy of the drugs. Both drugs were well tolerated and showed only few adverse reactions, which were comparable in severity and frequency. Iron protein succinylate led not only to a faster increase of hemoglobin, hematocrit, MCV, serum iron, and ferritin than iron hydroxide polymaltose complex, but the laboratory values remained higher in group A than in B even after 2 months of treatment.