Current Therapeutic Strategies in Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are the fastest growing chronic complication of diabetes mellitus, with more than 400 million people diagnosed globally, and the condition is responsible for lower extremity amputation in 85% of people affected, leading to high-cost hospital care and increased mortality risk. Neuropathy and peripheral arterial disease trigger deformities or trauma, and aggravating factors such as infection and edema are the etiological factors for the development of DFUs. DFUs require identifying the etiology and assessing the co-morbidities to provide the correct therapeutic approach, essential to reducing lower-extremity amputation risk. This review focuses on the current treatment strategies for DFUs with a special emphasis on tissue engineering techniques and regenerative medicine that collectively target all components of chronic wound pathology.

Serum cytokine, chemokine, and growth factor profiles and their modulation in inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn disease (CD) are the most common forms of inflammatory bowel disease (IBD). Because these subtypes of IBD are characterized by periods of activity and remission, an understanding of the modulation of biochemical markers with the clinical features of IBD or its treatment, may be useful for determining the correct treatment protocol.This study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with IBD, correlation with clinical findings of disease, and modulation according to the pharmacologic therapy.A case-control study was carried out in Zacatecas, Mexico. The 27 protein profiles of serum from 53 participants (23 UC, 11 CD, and 19 controls) were evaluated using the Pro Human Cytokine 27-Plex immunoassay (Bio-Rad).Considering the controls as a reference, the group with IBD endoscopic activity showed higher serum levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1 receptor antagonist (IL-1Ra), and platelet-derived growth factor BB (PDGF-BB) (P < .05). Interferon-induced protein 10 (IP-10) was associated with extraintestinal symptoms of disease (P = .041). Both PDGF-BB and interleukin 6 (IL-6) showed the strongest correlations with clinical features of IBD. Levels of IL-6, IL-7, and monocyte chemoattractant protein 1 were higher with 5-aminosalicylic acid (5-ASA) + Azathioprine therapy than controls (P < .05). Combined therapy with 5-ASA + Adalimumab led to the strongest changes in marker modulation: IL-4, IL-5, IL-15, and PDGF-BB, were upregulated (P < .05).Elevated serum levels of G-CSF, IL-1Ra, and PDGF-BB were associated with IBD endoscopic activity, and of IP-10 with extraintestinal manifestations of IBD. Combined therapy of 5-ASA + Adalimumab produced significant upregulation of IL-4, IL-5, IL-15, and PDGF-BB. This information may be useful for deciding on the course of pharmacologic therapy for patients with IBD and for generating new therapy alternatives to improve the outcome of patients with IBD.

Diabetic Foot Ulcers: Current Advances in Antimicrobial Therapies and Emerging Treatments.

Diabetic foot ulcers (DFUs) are very important diabetes-related lesions that can lead to serious physical consequences like amputations of limbs and equally severe social, psychological, and economic outcomes. It is reported that up to 25% of patients with diabetes develop a DFU in their lifetime, and more than half of them become infected. Therefore, it is essential to manage infection and ulcer recovery to prevent negatives outcomes. The available information plays a significant role in keeping both physicians and patients aware of the emerging therapies against DFUs. The purpose of this review is to compile the currently available approaches in the managing and treatment of DFUs, including molecular and regenerative medicine, antimicrobial and energy-based therapies, and the use of plant extracts, antimicrobial peptides, growth factors, ozone, devices, and nano-medicine, to offer an overview of the assessment of this condition.

The Influence of Obesity on Puberty and Insulin Resistance in Mexican Children.

Obesity is considered the main risk factor associated with the development of insulin resistance (IR). The aim of this study was to evaluate the influence of obesity on puberty onset and IR in Mexican children. A total of 378 children (189 boys and 189 girls) aged 8-14 years participated in the study. IR was estimated using the homeostasis model assessment for IR (HOMA-IR). The mean fasting glucose (FG) and basal insulin levels were 82 mg/dl and 11.0 µIU/ml in boys and 77.3 mg/dl and 12.3 µIU/ml in girls (P < 0.05). Subjects with obesity at Tanner stages II-V showed increased FG levels (P < 0.05). In boys with obesity, there was a decrease in HOMA-IR in Tanner stage IV and differences in age between boys with normal weight and those with obesity in Tanner V, being older the boys with obesity. Obesity in children and adolescents was associated with higher HOMA-IR values. In boys with obesity, IR increased at the end of pubertal maturation, with a delay in puberty. These findings should be considered on the establishment of IR cutoff values for pubertal population in Mexico and in the establishment of strategies to prevent the health problems related to obesity.

Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study.

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10-4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04-53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52-22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity.

Early pregnancy protein multiplex screening reflects circulating and urinary divergences associated with the development of preeclampsia.

BACKGROUND: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia. OBJECTIVE: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins. METHODS: We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex ProTM Human Cancer Biomarker Panels 1 and 2. RESULTS: The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8-29.8 times in the study population. CONCLUSION: The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered.

Matrix metalloproteinase multiplex screening identifies increased MMP-2 urine concentrations in women predicted to develop preeclampsia.

BACKGROUND: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia. OBJECTIVE: The objective of this study is to evaluate the usefulness of nine urinary metalloproteinases to predict the risk of preeclampsia development. METHODS: MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 were analyzed in urine (early-pregnancy) from 17 women predicted to develop preeclampsia and 48 controls using the Bio-Plex Pro-Human MMP panel (Bio-Rad, Hercules, CA). RESULTS: Urinary MMP-2 showed differences between groups which allowed us to calculate an increased risk for PE development of up to 20 times among the study population. CONCLUSION: Increased urinary concentration of MMP-2 at 12 and 16 weeks of gestation predicted an increased risk of developing preeclampsia in the study population.

Maternal distress and the development of hypertensive disorders of pregnancy.

Despite the implementation of programmes to improve maternal health, maternal and foetal mortality rates still remain high. The presence of maternal distress and its association with the development of pregnancy hypertensive disorders is not well established. The aim of this study was to evaluate the association between maternal distress and the development of hypertensive disorders in pregnancy in a prospective cohort of 321 Mexican women. Symptoms of maternal distressing were evaluated at week 20th of gestation using the General Health Questionnaire. The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the odds of developing a pregnancy hypertensive disorder by 5.1-26.4 times in study population (p values < .05). Our results support the participation of maternal distress in the development of hypertensive disorders of pregnancy. The implementation of effective programmes prioritising risk factors during pregnancy including the presence of maternal distressing factors is recommended. Impact statement What is already known on this subject: Changes in the nervous, endocrine, and immune systems have been observed in pregnant women with distress conditions leading to gestational disorders. What do the results of this study add: The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the developing of hypertensive disorders in Mexican population. What are the implications of these findings for clinical practice and/or further research: These findings may contribute to a better understanding of the role of the maternal stress in the development of hypertensive disorders of pregnancy, and in the implementation of effective programmes for clinical practice prioritising risk factors during pregnancy, including the presence of maternal distressing factors.