Severe Ulceration Research Articles

Anti-oxidant and anti-inflammatory potential of different polymer-based mesalamine delayed-release granules in TNBS-induced ulcerative colitis in wistar rats

Ulcerative colitis (UC) is an inflammatory condition of colon characterized by severe damage to the innermost colon tissues. A number of studies described the use of medication delivery systems based on natural polymers like polysaccharides for the purpose of reaching the colon. In this research, polymer-based mesalamine delayed-release granules (DRGs) were tested for their antioxidant and anti-inflammatory efficacy against UC. Chitosan (C), pectin (P), and pectin-chitosan (PC) mesalamine (M) DRGs were prepared and characterized. Data revealed satisfactory compatibility, flow, packing properties, drug release pattern, and delayed drug release by DRGs. Wistar rats were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (100 mg/kg) via rectal administration. Mesalamine and mesalamine DRGs (50 mg/kg) were administered orally separately for 14 days. Biomarkers of oxidative stress, inflammation, hematological tests, colon profile, and histopathology were performed. The findings demonstrated the good efficacy of the polysaccharides in delivering mesalamine to colon. Mesalamine and mesalamine DRGs based on various polymers showed significant antioxidant and anti-inflammatory effects in rats with UC. Mesalamine granules significantly attenuated colon lipid peroxidation, nitrites, myeloperoxidase activity, and interleukin-1β levels, and improved anti-oxidants (GSH, SOD). Data showed upregulation of Nrf2 activity by mesalamine granules with CM-DRGs showing maximum effect. Mesalamine and different polymer-based mesalamine DRGs significantly attenuated TNBS-induced decline in body weight, ulcer severity, and colon damage. CM-DRGs showed the most pronounced ameliorative effect on colon and hematology parameters via anti-oxidant and anti-inflammatory activities. Chitosan can be used as a carrier for oral colon delivery of mesalamine in DRG formulation for enhanced therapeutic efficacy in UC.

Isolation and identification of vapA-absent Aeromonas salmonicida in diseased snakehead Channa argus in China.

Aeromonas salmonicida is the typical pathogen causing furunculosis, reported widely in salmonids. Because of multiple serotypes, the control of A. salmonicida-caused disease has increasingly received much attention. Recently, A. salmonicida infection was reported in non-salmonid fish species. Here, a pathogenic A. salmonicida, named as As-s, was isolated from cultured snakehead (Channa argus) in a local fish farm in Shandong, China. As-s displayed clear hemolysis, amylase, and positive catalase activities, and grew at a wide range of temperatures (10-37 °C) and pH values (5.5-8.5). As-s was highly sensitive to cefuroxime sodium, ceftriaxone, ceftazidime, piperacillin, and cefoperazone and also apparently sensitive to chloramphenicol, erythromycin, and 25% cinnamaldehyde. The Virulence array protein gene cloning' results suggested that As-s has this gene compared with the other two vapA-containing strains, despite a close relationship of these strains via phylogenetic analysis. Severe ulcers on skin, muscle, and abnormal liver, and hemorrhage in pectoral/ventral fins and anal region were observed, and exophthalmos were also noticed in infected juvenile snakehead, as well as necrosis and infiltration of blood cells emerged in the internal organs using pathological section. In addition, As-s caused high mortality in snakehead, consistently with its immune gene response. This study reports the first isolation of vapA-absent A. salmonicida in snakehead.

Application of HBOT and Wolf Grafting in Chronic Diabetic Foot Ulcer

Diabetic foot ulcers are a serious complication of poorly controlled diabetes, often leading to amputations. This study presents a 60-year-old man with diabetes and severe foot ulcers who opted for a Wolfe skin graft with Hyperbaric Oxygen Therapy (HBOT) instead of amputation. Key points of study 1. The patient had poorly controlled diabetes and severe foot ulcers, resulting in 2 amputated toes. 2. Further amputations were anticipated for a chronic Wagner 3 diabetic ulcer. (Wagner, et. al., Foot and Ankle international) 3. A Wolfe skin graft limited debridement and minimally invasive surgery followed by HBOT sessions were successful in healing the ulcers and saving the toe. 4. This approach shows promise as an alternative to amputation for diabetic foot ulcers, potentially reducing costs and improving patient outcomes. Overall, this study suggests that Wolfe skin grafting combined with HBOT can be a viable alternative to amputation for treating diabetic foot ulcers. This approach may offer cost savings and improved quality of life for the patient by preserving limbs.

Clinical case of successful surgical treatment of arteriovenous malformation of the thumb finger

The management of arteriovenous malformations of the hand is one of the most difficult problems in vascular surgery. It’s primarily related to the number of vessels and nerves involved in the pathological process on a very limited anatomical area. Commonly the required steps of the diagnostic process are the following: clinical examination, Doppler colour flow mapping, MRI with intravenous contrast, angiography and thermography. There are various methods ofsurgical treatment of patients with arteriovenous malformation of the hand. Generally, they might be classified as endovascular and open-surgical ones. Endovascular methods, such as embolization and sclerotherapy, are associated with the risk of severe complications such as soft tissue necrosis, distal vascular bed-specific thrombosis, along with both sensory and motor connectivity of the hand. However minimally invasive procedures do not always contribute to an appropriate clinical result. This article presents an example of successful surgical treatment of a patient with arterio-venous malformation of the thumb finger with severe pain syndrome and recurrent bleeding ulcers. A radical removal of the malformation-bearing tissue with preservation of the arterial blood supply was performed under an arterial tourniquet. At the one-year post-surgery follow-up examination, the patient noted the absence of pain syndrome and ulcers, restoration of mobility in the interphalangeal and metacarpophalangeal joints. Thus, the treatment of arteriovenous malformation of the hand should be based on the latest research findings and the most advanced testing technologies. This clinical case demonstrates that open surgery can be considered as an effective and sustainable clinical approach with a good medium-term outcome for the patients with arteriovenous malformation of the hand.

Our experience of gamma-irradiated sterile cornea allograft surgery

Background: Gamma-irradiated sterile cornea (GISC) is a non-immunogenic, cross-linked, sterile patch graft in which the donor keratocytes and endothelial cells are eliminated. It can serve as a graft to cover glaucoma drainage devices, as a graft tissue for frank or impending corneal perforations in tectonic keratoplasty, as a graft tissue in lamellar keratoplasty, and as a carrier tissue for keratoprosthesis. The authors present their experience in treating severe ulcers with microperforations using GISC. Methods: In 2021, eight patients with corneal ulcers unresponsive to medical treatment were chosen to be candidates for VisionGraft® (Corneagen) GISC transplantation and underwent successful corneal surgery. Results: In 6 out of the 8 patients, the patch graft successfully restored tectonic support until optical keratoplasty could be performed if decision was made to improve visual acuity later. The remaining 2 grafts did not epithelialize after surgery and developed sterile corneal melt. Conclusion: This case series supports the use of VisionGraft® GISC as a graft for restoring the anatomy of the eyeball in the setting of corneal perforation.

Development of famotidine-loaded lecithin-chitosan nanoparticles for prolonged and efficient anti-gastric ulcer activity

Lecithin-chitosan nanoparticles (LCNPs) represent an appealing nanocarrier for the oral delivery of hydrophobic drugs. Negatively charged lecithin and positively charged chitosan were permitted to interact to create LCNPs. Their distinctive features enable drugs to be encapsulated into the lipophilic lecithin core while improving their retention in gastric mucosa by the chitosan coat. Famotidine (FMD), a hydrophobic H2-receptor antagonist drug with a short half-life (2.5–4 h), was loaded into LCNPs to enhance its therapeutic efficacy in gastric ulcers through achieving good mucoadhesion and subsequent absorption. The optimal formula with a lecithin to chitosan ratio of 10:1 was selected and exhibited a particle size of 178.5 ± 9.5 nm, a zeta potential of 43.7 ± 2 mV, and an entrapment efficiency of 75.81 ± 2.5 %. It displayed a prolonged in vitro release profile (75.72 % over 24 h) and considerable mucoadhesive properties. FMD-LCNPs were also characterized by differential scanning calorimetry, Fourier transform-infrared (FTIR) spectroscopy, transmission electron microscopy, and stability studies. The in vivo study was performed on ethanol-induced gastric ulcer in a rat model, and the anti-gastric ulcer effects of FMD-free, FMD-marketed product, and FMD-LCNPs were determined by assessing the ulcer severity, antioxidant biomarkers, eNOS levels in addition to histopathological examination. FMD-LCNPs administration resulted in a percentage of protection from gastric severity of 96.25 % and an exceptional ameliorative effect on oxidative stress biomarkers (GSH; 162.36 % increase and MDA; 71.91 % decrease) as compared to other FMD forms. Additionally, FMD-LCNPs showed the strongest eNOS level improvement (130.34 %), which indicated the best healing impact and was confirmed by restoring the gastric mucosa to normal architecture.

Characteristics of Inflammatory Markers in Diabetic Foot Patients and Their Relationship With Prognosis of Diabetic Foot Ulcers

To explore the characteristics of baseline inflammatory markers in diabetic foot patients and their relationship with the prognosis of diabetic foot ulcers. The clinical data of diabetic foot patients (n=495) admitted to West China Hospital, Sichuan University since 2016 were retrospectively collected through the hospital electronic medical record system to analyze the characteristics of inflammatory markers and their relationship with the prognosis of diabetic foot ulcers. White blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels were significantly higher in patients defined as grade 4 on the Wagner Scale than those in patients defined as grade 0-3 on the Wagner Scale. Neutrophil percentage (NE%) was higher in Wagner grade-4 patients than those in Wagner grade-0 and grade-1 patients and higher in Wagner grade-3 patients than those in Wagner grade-0 patients. NE%, CRP, PCT, and IL-6 levels were positively correlated with the severity of diabetic foot, with the respective odds ratio (OR) at 95% confidence interval (CI) being 1.038 (1.019-1.056), 1.019 (1.012-1.026), 8.225 (2.015-33.576), and 1.017 (1.008-1.025). Using Wagner grade-0 patients as the reference, patients with higher WBC were more likely to progress to Wagner grade 2, 3, and 4, with the respective OR (95% CI) values being 1.260 (1.096-1.447), 1.188 (1.041-1.356), and 1.301 (1.137-1.490); patients with higher ESR were more likely to progress to Wagner grade 3 and 4, with the respective OR (95% CI) values being 1.030 (1.006-1.054) and 1.045 (1.019-1.071). Baseline ESR (P=0.008), CRP (P=0.039), and IL-6 (P=0.033) levels were lower in patients who had received antibiotics prior to their admission than those in patients who had not received antibiotics before admission. The levels of WBC, NE%, ESR, PCT, and IL-6 were lower in the full recovery group than those in the group of patients who did not respond to treatment. The higher the levels of NE% and IL-6, the worse the prognosis of diabetic foot ulcers became, with the respective OR (95% CI) values being 1.030 (1.010-1.051) and 1.008 (1.002-1.013). The severity of diabetic foot ulcers increased with the rise in baseline levels of inflammatory markers. Elevated baseline NE% and IL-6 levels suggest a poor prognosis. Our findings suggest that early assessment of diabetic foot infection and standardized antibiotic therapy should be implemented to improve the prognosis.

Investigating the gastrointestinal physiology of mature horses with and without a history of cribbing behavior in response to feeding a digestive support supplement

Cribbing, a stereotypic oral behavior observed in horses, involves placing incisors on a fixed object, arching the neck, pulling against the object, and emitting an audible grunt. This behavior has been associated with gastrointestinal (GI) dysfunction and gastric ulceration. In this randomized crossover study, we investigated the impact of a GI support supplement (SPL) on the GI environment and physiology of four cribbing (CB) and four non-cribbing horses (NCB). Mature Quarter Horses, acclimated to individual stalls for 16 hours daily with paddock turnout in pairs for 8 hours per day, were randomly assigned to receive either the SPL or placebo for 21 days, followed by a 2-week washout period. Fecal and gastric samples were collected for pH determination and blood samples were analyzed for serum cortisol and gastrin levels. Endoscopic examinations assessed gastric ulcer severity, and cribbing frequency and bouts were recorded via video surveillance. Data were analyzed using a mixed-model ANOVA. Results showed no differences in fecal and gastric pH between cribbing statuses. However, an interaction between supplementation and cribbing status was observed for squamous mucosa ulcer scores (P=0.003). There were no differences in glandular mucosa ulcer scores, serum cortisol, serum gastrin, and crib-bite count between CB and NCB horses or between supplementation groups. Crib-bout duration did not differ with supplementation, but differences were found between periods (P<0.05) and hour ranges (P<0.001). Our findings suggest that the GI support supplement may not effectively address cribbing behavior or alter the GI environment in NCB or CB horses.

Tracheal ulcer development from high volume, low-pressure cuffed endotracheal tubes

IntroductionIatrogenic injury to the larynx, particularly the vocal cords from prolonged intubation, has been well-studied; however, tracheal injuries are rarely reported. This study investigates the effectiveness of cuffed, high-volume, low-pressure endotracheal tubes in preventing the development of tracheal ulcers in intubated subjects. MethodsA retrospective, IRB-approved review was performed on 1355 subjects who underwent percutaneous tracheostomy from 2002 to 2018. The presence and severity of tracheal ulcers were collected using documentation and photos during percutaneous tracheostomy placement. Primary outcome measures included: the length of time on a ventilator until tracheostomy (LOVT), length of hospitalization (LOH), and mortality in relationship to the severity of the tracheal injury. Data was reported as n (%) and median (IQR). The differences in means between groups were analyzed by ANOVA and Chi-square test with an alpha of 0.05. Results206 subjects met the inclusion criteria; 65 subjects had an absence of tracheal injury, and 141 subjects developed tracheal ulcers. Subjects with tracheal ulcers were grouped by the following severity scale: no ulcer; mild ulcer (minimal mucosal erosion with exudate); moderate ulcer (mucosal erosion); and severe (tracheal ring exposure). There were no statistically significant differences in age (p = 0.99), gender (p = 0.83), BMI (p = 0.44), LOH (p = 0.88), LOVT (p = 0.93), and mortality (p = 0.306) between subjects with differing severity of ulcers. The average annual incidence of clinically significant ulcers (moderate and severe) was 2.2 %. ConclusionsThe lack of statistical correlation between the duration of intubation and tracheal ulcer severity, along with a low annual incidence of tracheal ulcers, supports the improved safety of high-volume, low-pressure cylindrical, cuffed endotracheal tubes. This study is among the first to specifically focus on injuries at the level of the cuff and tip of endotracheal tubes with implications in preventive measures and potential product design changes.

Gastric Ulcer Mechanism, Protection and Treatment from Natural Sources

Gastric acid secretions are main cause for formation of gastric ulcers that are attributed by Helicobacter pylori infection and extensive use of NSAIDs (non-steroidal anti-inflammatory drugs). These contributors facilitate the initiation of cellular and molecular signalling pathways in our body that give rise to formation of gastric ulcer. Generally, gastric ulcer results in minute to deep invading of gastric mucosal linings which may produce harmful symptoms in our body. Non-infectious gastric ulcers are another problem related with gastro-intestinal disorders that mainly caused because of poor daily activities including alcohol consumption, oxidative stress, mental stress and low consumption in healthy food intake. Stress plays a crucial role in the formation gastric ulceration due to its effect on the generation of ROS (reactive oxygen species) and RNS (reactive nitrogen species).Gastric cancer is found common in severe ulceration and gastric lesions. This type of cancer mainly attributed by untreated gastric ulcer and other related infected and inflammatory conditions. They all increase the worldwide incidence of morbidity and mortality rates. Therefore, a novel approach towards research and development has been must to categorise these complications. Natural agents with adaptogenic and antioxidant properties are useful in this situation. Some of the herbal extracts have been used from ancient times due to their cytoprotective, anti-inflammatory and antioxidant effects. New approaches are still on progress to obtain a potential phytopharmaceutical and natural agent to treat these disorders. It has been reported anti-secretory effects of herbal preparations give rise to protective action in the cure of gastric ulcers. We try to explain mechanisms involve in this complication and important pharmacological activity of natural extracts to counter act these symptoms in our review.

Adherence to the Mediterranean Diet in Italian Patients With Systemic Sclerosis: An Epidemiologic Survey.

Systemic sclerosis (SSc) is an orphan disease that can lead to severe involvement of the gastrointestinal tract with a significant impact on patients' quality of life (QoL). The Mediterranean diet (MD) was consistently demonstrated to have beneficial effects on chronic diseases based on biological bases. We aimed to evaluate the adherence to the MD of Italian patients with SSc to preliminarily assess its association with gastrointestinal symptoms and other disease features, mood, and QoL. In this cross-sectional study, adherence to the MD was measured in 387 patients from four SSc Italian referral centers through the 14-item Mediterranean Diet Adherence Screener (14-MEDAS) questionnaire. We also registered patients' reported outcomes related to the QoL and mood. Overall, an optimal adherence to MD was observed in 14.7% of patients with SSc, a moderate adherence in 71.3%, and a low adherence in 14.0%. In univariate analysis, poor adherence to the MD was associated with a more prominent depressive mood, time missed at work, and perception of more severe Raynaud's phenomenon and digital ulcers, whereas the 14-MEDAS score inversely correlated with depression score and reflux. In our cohort of patients with SSc, overall adherence to MD was moderate. Patients with lower adherence to MD also reported worse outcomes related to QoL and mood. Administration of the 14-MEDAS could be a reasonable choice to assess adherence to the MD in patients with SSc. Future initiatives to study the role of MD in the management of patients with SSc are warranted.

Thigh Abscess Formation Due to Severe Sacral Pressure Ulcer Dissemination: A Case Report

Patients with chronic and non-healing pressure ulcers are susceptible to recurrent infections, often leading to complications, such as abscesses. However, to the best of our knowledge, no cases of abscesses disseminating from a pressure sore to the thigh have yet been reported in the literature. We report the case of a 53-year-old man with a severe pressure ulcer in the sacral area and an abscess extending to the thigh. The presence of an abscess in an area devoid of pressure ulcers was suspected. Prior to surgical intervention, a comprehensive evaluation was undertaken, culminating in debridement and subsequent reconstruction, yielding excellent results. Abscesses are often difficult to evaluate with physical examination alone. Therefore, the possibility of extensive abscess formation and dissemination should be considered in patients with severe pressure ulcers.

Stepping up foot care: assessment over foot care knowledge and behavior among individuals with diabetes of risk levels

BackgroundDiabetic foot is a global threat to public health, as it can lead to infections and amputations and cause significant pain and economic costs for patients. Diabetic foot patients in northern China have more severe local ulcers, worse prognosis, and longer disease duration.ObjectiveThis study assessed the foot risk levels and foot care knowledge and behavior status of people with diabetes with different foot risk levels, and investigated the factors that influence the occurrence of high-risk foot in diabetes.MethodsThis cross-sectional survey included 410 hospitalized people with diabetes. Demographic and disease-related data and foot risk stratification status were collected using investigator-designed questionnaires. Foot care knowledge and behavior questionnaires were also used.ResultsAmong the 410 participants, a total of 367 cases were classified as high-risk feet, among which 135 cases were rated as grade 1, 202 cases grade 2, and 30 cases grade 3. Foot care knowledge surveys revealed low scores in the areas of shoe and sock selection, foot and footwear examination, and management of foot problems. Foot care behavior surveys showed low scores in the areas of foot and footwear examination, management of foot problems, and foot injury risk behavior. One-way ANOVA revealed significant differences in foot care behaviors among patients with different foot risk classifications (p < 0.05), while no significant differences were observed in foot care knowledge scores. Multivariate logistic regression analysis showed that age, history of cerebrovascular disease, and foot care behavior scores were factors influencing the occurrence of high-risk foot in people with diabetes.ConclusionThe results of this study showed a high prevalence of high-risk foot in diabetics; The knowledge and behavior of foot care in diabetics with different foot risk levels were both at a moderately low level; There were differences in foot behavior scores among patients with different foot risk classes, but, counter-intuitively, no significant differences in foot care knowledge. The study found that advanced age, history of cerebrovascular disease, and low foot care behavior scores are risk factors for high-risk foot in diabetes. Therefore, it is necessary to screen patients with diabetes for high-risk feet and implement targeted interventions according to the results.

Diagnosis and treatment of a case of severe oral mucosal traumatic ulcer in a child with Tourette syndrome

Diagnosis and treatment of a case of severe oral mucosal traumatic ulcer in a child with Tourette syndrome

Proteomic characteristics of six snake venoms from the Viperidae and Elapidae families in China and their relation to local tissue necrosis

Patients envenomed by snakes from the Viperidae and Elapidae families in China often have varying degrees of local tissue necrosis. Due to the relative clinical characteristics of local tissue necrosis and ulceration following envenoming, this study has analyzed the proteome of six snake venoms from the Viperidae and Elapidae family, and the toxin profiles of each snake were compared and correlated with the clinical manifestations that follow cytotoxic envenoming. Deinagkistrodon acutus and Naja atra envenomation induce severe ulceration, which is absent in Bungarus multicinctus envenomation and mild in the other three vipers. It is interesting to note that the proportion of c-type lectins (CTL) (20.63%) in Deinagkistrodon acutus venom was relatively high, which differs from the venom of other vipers. In addition, three-fingered toxin (3FTx) (2.15%) is present in the venom of Deinagkistrodon acutus, but has not been detected in the remaining three vipers. Snake venom metalloprotease (SVMP) (34.4%–44.7%), phospholipase A2 (PLA2) (9.81%–40.83%), and snake venom serine protease (SVSP) (9.44%–16.2%) represent the most abundant families of toxin in Viperidae venom. The Elapidae venom proteome was mainly composed of neurotoxins and cytotoxins, including 3FTx (39.28%–60.08%) and PLA2 (8.24%–58.95%) toxins, however, the proportion of CRISPS (26.36%) in Naja atra venom was relatively higher compared to Bungarus multicinctus venom. Significant differences in SVMP, SVSP, and 3FTx expression levels exist between the Viperidae and the Elapidae family. The main toxins responsible for the development of tissue necrosis and ulcerations following Viperidae envenoming are hematotoxins (SVSMP, SVSP) and myotoxins (PLA2). Deinagkistrodon acutus venom contains high levels of CTL and traces of 3FTx, leading to more severe local necrosis. However, Naja atra venom can also cause severe local necrosis through the effects of myotoxin (3FTx, CRISP, PLA2). Bungarus multicinctus venom does not contain myotoxins, resulting in pure systemic neurological manifestations no obvious necrosis of local tissue in patients.

Anti-ulcer activity of aqueous ethanol extract of Rheum spiciforme and its fractions in animal model

Helicobacter pylori infection, pepsin, ischemia, hypoxia, smoking, alcohol intake, hydrochloric acid, and nonsteroidal anti-inflammatory drugs are the causal factors of ulceration. In third-world countries, approximately one in two individuals has signs of gastric ulceration. Extensive literature suggested that plant-derived drugs hold the potential in the treatment of peptic ulcer, and Rheum spiciforme (family: Polygonaceae) has been known in the folk medicine for possessing medicinal effect on ulceration. To explore further along this line, the current study was designed to investigate the effects of aqueous ethanol extract of R. spiciforme roots and its fractions on peptic ulcer and to identify bioactive compounds responsible for mitigating this pathological condition. Animal model of ethanol-induced gastric ulcer was utilized in this study. The animals were pre-treated with crude plant extract, given at doses 125, 250, and 500 mg/kg, and then orally administered with butanol, aqueous, and dichloromethane fractions at doses of 250 mg/kg for 7 days. Following the treatments, a significant decrease in ulcerative lesions, ulcer index, ulcer severity score, volume, free acidity, and total acidity of gastric juice as well as a marked increase of gastric pH in the groups treated with plant extract at doses of 250 and 500 mg/kg were noted. Moreover, butanol fraction has been shown to produce effects equipotent to that of the reference drug omeprazole. Liquid chromatography-mass spectrometry analyses show that the plant extract contains emodin, aloe-emodin, and quercetin. In conclusion, this study demonstrated that the aqueous ethanol extract of R. spiciforme and its butanol fraction exhibited gastro-protective effect.

ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon

Raynaud’s phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10−8). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10−27) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12–1.22, p < 4.8 × 10−13) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (rG = −0.21; p-value = 2.3 × 10−3), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α2A-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.

Effects of Vitamin B on experimentally induced gastric ulcers in rodents

Background: Peptic ulcer disease (PUD) is associated with water soluble vitamin deficiencies. B group vitamins play vital roles in maintenance of essential body functions. PU patients are found to present with Vitamin B deficiency and high rates of Helicobacter pyloric infection. This study aims to investigate the effect of vitamin B (VB) on experimentally induced gastric ulcers in mice Method: Gastric ulcers were induced in adult Swiss albino mice using absolute ethanol, a nonsteroidal anti-inflammatory agent, diclofenac and acetic acid. Animal were treated for 7 days with vitamin B at 12.5, 25 and 50 mg/kg before ulcer induction with ethanol and diclofenac, while in the acetic acid induced ulcers, treatment (VB 50 mg/kg) was administered for 14 and 28 days post ulcer induction. The degree of gastric ulceration was scored after which tissues subjected to histological analysis Results: The results showed that vitamin B ameliorated ulceration caused by absolute ethanol, diclofenac and acetic acid. In the ethanol induce ulcer, pretreatment with VB produced dosedependent reduction in severity of ulcer when compared to control group. Ulceration of gastric mucosa was inhibited by 3.57%, 23.86% and 55.71% at 12.5, 25 and 50 mg/kg of VB respectively. Omeprazole produced an inhibition of 69.71% at 20mg/kg. VB similarly inhibited diclofenac induced ulceration by 54.31%, 69.05% and 78.94% respectively at tested doses, while omeprazole had 87.79%. For the acetic acid-induced ulcer animals, treatment significantly increased pH of gastric contents when compared with control. Histological analysis revealed dose-dependent (ethanol and diclofenac) and time - dependent (Acetic acid) decrease in severity of damage caused by the ulcerogens on treatment with VB Conclusion: These findings suggest that vitamin B possesses potential gastro-protective effects.

Topical betamethasone and systemic colchicine for treatment of recurrent aphthous stomatitis: a randomised clinical trial

BackgroundRecurrent Aphthous Stomatitis (RAS) is painful oral ulceration frequently treated with topical steroids. There is limited published evidence for the efficacy of any treatment for RAS and there remains a need for longitudinal randomised clinical trials to evaluate and compare the effectiveness of different therapies in the management of RAS. The aim of the current project was to assess the efficacy of betamethasone mouthwash and colchicine tablets, individually and combined, for the treatment of RAS, and to establish the optimum treatment period necessary for a significant reduction in the disease severity.MethodologyA randomised, prospective, parallel-group clinical trial was conducted over one year, to compare the efficacy of three therapies in RAS. One hundred and six patients were randomized into three groups; 35 received betamethasone mouthwash, 35 had colchicine tablets and 36 received both therapies. The response was evaluated quantitatively every 3 months for 1 year, using the Ulcer Severity Score (USS).ResultsFor all three treatment regimes, the mean USS decreased by about 30% in the first 3 months (p < 0.001). Further improvement was noted for up to 9 months. At the end of the study, the mean USS had improved by 50% from 34.9 ± 7.2 before treatment to 17.5 ± 8.9 after treatment (p < 0.001). Of included participants, 86% showed significant clinical improvement by the end of the study. There were no significant differences in outcomes between the three regimes (p < 0.05).ConclusionsThis clinical trial has provided evidence for the efficacy of betamethasone mouthwash and for colchicine tablets in the treatment of RAS and has shown that at least six months of treatment may be required for optimum effect.Clinical trial registration number:ISRCTN3267716. Date of clinical trial registration: 15/04/2018

Proximal Tibial Cortex Transverse Distraction Facilitating Healing and Limb Salvage in Severe and Recalcitrant Diabetic Foot Ulcers

Category: Diabetes; Diabetes Introduction/Purpose: The management of severe and recalcitrant diabetic foot ulcers is challenging. Distraction osteogenesis is accompanied by vascularization and regeneration of the surrounding tissues. The longitudinal distraction of the proximal tibia stimulates increased and prolonged blood flow to the distal tibia. However, the effects of the transverse distraction of the proximal tibia cortex on severe and recalcitrant diabetic foot ulcers are largely unknown. Methods: Between July 2014 and March 2017, we treated 136 patients with diabetes and severe ulcers (University of Texas Grade 2B to 3D) that had not responded to treatment for at least 6 months. and their ulcers had a mean ± SD area of 44 cm2 ± 10 cm2. All 136 patients underwent tibial cortex transverse distraction. We compared these patients with the last 136 consecutive patients we treated with standard surgical treatment between May 2011 and June 2013; All patients received standard off-loading and wound care. We compared the groups with respect to ulcer healing (complete epithelialization without discharge, maintained for at least 2 weeks) in a 2-year follow-up, the proportion of ulcers that healed by 6 months, major amputation, recurrence, and complications in the 2-year follow-up. Foot arterial status and perfusion were assessed in the TCTD group using CT angiography and perfusion imaging. Results: The tibial cortex transverse distraction group had a higher proportion of ulcers that healed in the 2-year follow-up than the control group (96% versus 68% ; p &lt; 0.001). By 6 months, a higher proportion of ulcers healed in the TCTD group than in the control group (93% versus 41% ; p &lt; 0.001). Lower proportions of patients in the TCTD group underwent major amputation (2.9% versus 23%; p &lt; 0.001) or had recurrences 2.9% versus 17%, OR 0.20 [95% CI 0.05 to 0.45]; p &lt; 0.001) than the control group in 2-year follow-up. In the feet of the patients in the TCTD group, there was a higher density of small vessels and higher blood flow and blood volume 12 weeks postoperatively than preoperatively. Conclusion: Proximal tibial cortex transverse distraction substantially facilitated healing and limb salvage and decreased the recurrence of severe and recalcitrant diabetic foot ulcers. The surgical techniques were relatively straightforward although the treatment was unorthodox, and the complications were few and minor. These findings suggest that tibial cortex transverse distraction is an effective procedure to treat severe and recalcitrant diabetic foot ulcers compared with standard surgical therapy. Randomized controlled trials are required to confirm these findings.