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1.
Foot Ankle Orthop ; 9(1): 24730114241241269, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38559393

RESUMEN

Background: Combining osteotomies and soft tissue procedures is believed to reduce sesamoids in their anatomical position and maintain long-term correction when treating hallux valgus deformity. This study determines if a radiologic association exists between a radiolucent sign and a full percutaneous adductor tendon release (PATR), including a cadaveric study and a consecutive case series. Another aim was to determine the intra- and interobserver reliability of these observations. Methods: A prospective observational study was made between 2018 and 2019. First, a PATR was done on cadaveric specimens and, after the procedures, dissected to correlate what was seen fluoroscopically. The clinical group included 39 feet that presented mild-to-moderate HV deformity and were treated with percutaneous osteotomies associated with PATR. Results: Observers 1 and 2 saw a radioscopic radiolucent sign in 100% of cadavers and the patient population. They also observed a triangle-shaped image with an incidence of 75%, which we have named the "triangle sign." Conclusion: The triangle sign may be helpful in the intraoperative confirmation of PATR and latero-plantar capsule release using this percutaneous technique. Level of Evidence: Level II, development of diagnostic criteria.

2.
J Foot Ankle Surg ; 62(3): 432-436, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36402635

RESUMEN

Pronation of the first metatarsal is a risk factor for the formation and progression of the hallux valgus deformity. Recently, Yamaguchi et al published a study that showed how the round sign increases on digitally reconstructed radiography taken from a CT scan when pronation is applied. In this study, the shape of the lateral edge of the first metatarsal head was evaluated on weightbearing dorsoplantar radiographs. Yamaguchi's signs were presented to observers after the visual presentation of each foot as an image. The best-fit circle was drawn using the PACS drawing function. Ninety radiographs of adults presenting hallux valgus deformities were classified as mild-to-moderate, based on hallux valgus angle and intermetatarsal angle. The global average observations were 3.72 ± 3.92 (range 2.3°-4.6°). The interclass correlation (Fleiss Kappa index κ = 0.225) and the Spearman correlation (0.16 of Kappa) coefficients were poor for interobserver measurements and statistically significant. Using the linear model, there was no significant variability between the repetitions corresponding to each observer (t-value -1.527, p value .127). Our findings show that the Yamaguchi method can be very subjective and should not be the exclusive technique to assess the rotation of the first metatarsal or head roundness.


Asunto(s)
Juanete , Hallux Valgus , Hallux , Huesos Metatarsianos , Adulto , Humanos , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Huesos Metatarsianos/diagnóstico por imagen , Huesos Metatarsianos/cirugía , Pronación , Reproducibilidad de los Resultados
3.
Foot Ankle Int ; 43(8): 1022-1033, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35642681

RESUMEN

BACKGROUND: Bunionette deformity is described as a painful bony prominence on the lateral aspect of the fifth metatarsal head. The present study prospectively assessed the clinical, functional, and radiographic outcomes of sliding distal metatarsal minimally invasive osteotomy (S-DMMO) used in a large series of patients with a midterm follow-up period. METHODS: From December 2015 to December 2018, we evaluated 74 feet (57 patients). Radiologic (4-to-5 intermetatarsal angle, fifth metatarsophalangeal angle, the fifth metatarsal head width, lateral deviation angle, fifth metatarsal length, medial displacement, and elevation), clinician-reported scores (AOFAS score, visual analog scale [VAS]) and patient-reported outcomes measure (Foot and Ankle Ability Measure [FAAM] activities of daily living [ADL], FAAM sports, Manchester-Oxford Foot Questionnaire [MOXFQ], and patient satisfaction survey) were included in the analysis. The time to bone union was also assessed. RESULTS: The average 4-to-5 intermetatarsal angle improved from 11.1 degrees preoperatively to 4.5 degrees postoperatively (P < .001), whereas the average fifth metatarsophalangeal angle improved from 15.7 degrees preoperatively to 4.8 degrees postoperatively (P < .001). The lateral deviation angle was found to be 2.2 degrees. The fifth metatarsal length decreased from 66.6 to 64.3 mm postoperatively. The average initial medial displacement was 4.67 mm preoperatively and 4.54 mm at final follow-up. The elevation of the fifth metatarsal head was 1.08 mm. The American Orthopaedic Foot & Ankle Society score improved from 54.3 ± 20.86 points preoperatively to 93.4 ± 17.3 (P < .001). VAS score decreased from 7.9 to 0.7 (P < .001). Also, FAAM ALD, FAAM Sport, and MOXFQ showed statistically significant differences (P < .001) between preoperative and postoperative periods. Patients found the procedure excellent in 89.1% of cases, very good in 5.4%, and good in 5.4%. Bone union was obtained at 8.1 weeks. CONCLUSION: The most important finding of the present study is that S-DMMO showed improvement in function and pain associated with a high satisfaction rate. Also, we found substantial capacity to correct deformities and a low incidence of complications. LEVEL OF EVIDENCE: Level IV, case series.


Asunto(s)
Juanete de Sastre , Hallux Valgus , Huesos Metatarsianos , Actividades Cotidianas , Juanete de Sastre/diagnóstico por imagen , Juanete de Sastre/cirugía , Hallux Valgus/cirugía , Humanos , Huesos Metatarsianos/cirugía , Osteotomía/métodos , Resultado del Tratamiento
4.
Foot Ankle Spec ; : 19386400221079198, 2022 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-35236146

RESUMEN

PURPOSE: The expression "learning curve" indicates the relation between the time needed to learn a new technique and the technique-related outcome. Percutaneous surgery (also called "minimally invasive surgery") has experienced sustained and respectable growth, especially in forefoot deformities. The main purpose was to assess the number of feet necessary to become skilled in a specific minimally invasive surgery (MIS) procedure. METHODS: From January 2015 to June 2018, 46 consecutive patients were evaluated and included in the study. Patients were divided into 2 groups according to the surgery period: first 30 feet (Group 1), and subsequent 30 feet (Group 2) from the whole population evaluated. Age, body mass index, and operative time were evaluated. Hallux valgus angle and the 1 to 2 intermetatarsal angle were also measured. Patients were assessed according to the American Orthopedic Foot and Ankle Society (AOFAS) forefoot scale, the Foot and Ankle Ability Measure activities of daily living (FAAM ADL) subscale and the visual analog scale (VAS). RESULTS: The comparison of the 2 groups showed statistically significant differences in hallux valgus angle (HVA) but not in intermetatarsal angle (IMA). The mean improvement between pre- and postoperative FAAM ADL, VAS, and AOFAS score in Group 1 were 12.83, 3.93, and 24.77 points, respectively. In Group 2, the mean improvement between pre- and postoperative FAAM ADL, VAS, and AOFAS scores were 15.19, 4.3, and 24.5 points, respectively. The differences between groups in FAAM ADL score was statistically significant (P = 0.0364). Group 1 showed a global complication rate of 16.67% (n = 5) while group 2 showed 3,3% (n = 1). CONCLUSION: After the first 30 cases, radiographic, clinical, and functional outcomes substantially improved, and the level of the perioperative complications decreased. The results suggest that the learning curve plateau for performing a percutaneous subcapital osteotomy can be reached after 30 surgeries. LEVELS OF EVIDENCE: Level III.

6.
Int Orthop ; 45(9): 2251-2260, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34347130

RESUMEN

PURPOSE: Treatment for hallux valgus (HV) remains challenging. Third-generation percutaneous procedures try to reproduce chevron-type osteotomies to replicate their benefits, such as intrinsic stability and reproducibility. We report the first results using a percutaneous, intra-articular, chevron osteotomy (PeICO) technique that mimics the classic intra-articular open chevron procedure, associated with a percutaneous adductor tendon release (PATR) for the treatment of mild-to-moderate HV. METHODS: From May 2015 to October 2018, a total of consecutive 114 feet (74 patients) were included. Primary outcome measures included radiographic (hallux valgus and intermetatarsal angles) and clinical parameters such as visual analog scale (VAS), FAAM Activities of Daily Living (ADL), and FAAM Sport, AOFAS Score, and MOXFQ, preoperatively and at final follow-up (Minimum 18 months). A patient satisfaction survey was also performed. Pronation and length of the first metatarsal were also assessed. Secondary outcomes included fluoroscopic time, length of surgery, complications, recurrence, and re-operation rates. RESULTS: At 24.09 months on average, the AOFAS score improved from 52.1 points preoperatively to 91.1 (p < 0.001) at the latest follow-up. VAS decreased from 6.3 to 1. Also, FAAM ALD, FAAM Sport, and MOXFQ showed statistically significant differences (p < 0.001) when comparing pre-operative and post-operative periods. Patients found the procedure to be excellent in 82% and very good in 13.5% of cases. Our global complication and re-operation rates were 5.26% and 3.5% (screw removal), respectively. CONCLUSION: PeICO combined with PATR proved to be a safe, reliable, and effective technique for the correction of mild-to-moderate HV deformity.


Asunto(s)
Hallux Valgus , Actividades Cotidianas , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Humanos , Osteotomía , Reproducibilidad de los Resultados , Resultado del Tratamiento
7.
SAGE Open Med Case Rep ; 9: 2050313X211027094, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34350000

RESUMEN

Cryptococcus neoformans is an encapsulated, yeast-like fungus that can cause a systemic mycosis, particularly in immunocompromised patients. Disseminated infections typically affect the central nervous system, and osseous lesions are infrequent. Only 5%-10% of disseminated cryptococcosis involves bones. A 69-year-old female presented pain, swelling, and a soft tissue mass in her right lateral hindfoot. Her medical history included a kidney transplant (10 years earlier) secondary to chronic disease due to IgA nephropathy. The patient underwent an excisional biopsy, surgical debridement, and secondarily negative pressure wound therapy to achieve skin closure. Biopsy revealed a rare Cryptococcus neoformans osteomyelitis of the calcaneus. The patient then received IV treatment with liposomal amphotericin B at 3 mg/kg/d for 25 days. In conclusion, we present a case of cryptococcal osteomyelitis which, although not a frequent disease, must be considered as one of the differential diagnoses of osteolytic osseous lesions in patients with chronic osteomyelitis. Cryptococcus neoformans may be a potential cause of below-knee infection, mainly in immunocompromised patients.

8.
Nutrients ; 13(7)2021 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-34209507

RESUMEN

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague-Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.


Asunto(s)
Depresores del Apetito/farmacología , Ingestión de Alimentos/efectos de los fármacos , Endopeptidasa Clp/farmacología , Proteínas de Escherichia coli/farmacología , Proteínas de Choque Térmico/farmacología , Péptido YY/metabolismo , Animales , Anticuerpos Antibacterianos/metabolismo , Western Blotting , Técnicas de Cultivo de Célula , Fragmentación del ADN , Ensayo de Inmunoadsorción Enzimática , Escherichia coli/química , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas , Ratas Sprague-Dawley
9.
Rev Endocr Metab Disord ; 22(4): 1057-1071, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34037916

RESUMEN

Infertility is a global health problem affecting 10-15% of couples in reproductive age. Recent studies have provided growing evidence supporting that lifestyle factors can affect male fertility through alterations in endocrine profiles, spermatogenesis and/or sperm function. One of these critical factors could be the change in the food intake behavior in modern societies that produces metabolic alterations. Regarding this, metabolic syndrome (MetS) prevalence has increased in epidemic in the last 40-50 years. Although MetS is associated with advanced age, changes in lifestyles have accelerated the appearance of symptoms in the reproductive age. We review herein the current understanding of the relationship between MetS and the male reproductive status. For this purpose, in this narrative review a comprehensive literature search was made in both animal models and men, allowing us to evaluate such relationship. This analysis showed a high variability in the reproductive phenotypes observed in patients and mice suffering MetS, including sperm parameters, fertility and offspring health. In view of this, we proposed that the reproductive effects, which are diverse and not robust, observed among MetS-affected males, might depend on additional factors not associated with the metabolic condition and contributed not only by the affected male but also by his partner. With this perspective, this review provides a more accurate insight of this syndrome critical for the identification of specific diagnostic indicators and treatment of MetS-induced fertility disorders.


Asunto(s)
Infertilidad Masculina , Síndrome Metabólico , Animales , Fertilidad , Humanos , Infertilidad Masculina/etiología , Masculino , Síndrome Metabólico/etiología , Ratones , Espermatogénesis , Espermatozoides
11.
J Perioper Pract ; 30(11): 340-344, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32609069

RESUMEN

Inadvertent perioperative hypothermia is a frequent problem associated with surgical patients which can have significant consequences during surgery and in the immediate postoperative period. We compared 35 randomised patients using over vs. under body forced air heating. There were no statistically significant differences between some demographic and surgical parameters such as: age, weight, height, body mass index, length of anaesthesia and operation. Statistically significant differences were found between the patient's admission to the operating room and 30 minutes and the end of the procedure on the under body patients group. This study analyses a uniform population of patients (Foot and Ankle Surgery) previously not studied and supports the use of under body blankets.


Asunto(s)
Tobillo , Hipotermia , Ropa de Cama y Ropa Blanca , Temperatura Corporal , Calefacción , Humanos , Hipotermia/prevención & control , Periodo Posoperatorio
12.
SAGE Open Med Case Rep ; 8: 2050313X20919223, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32537160

RESUMEN

We present the case of a 43-year-old boy who presented with progressive pain as a result of history of lateral avascular necrosis of the talus secondary to traumatic open ankle luxation 20 years ago. Conservative treatment (12-month period) prior to surgery failed. It consisted of physiokinetic treatment, insoles and analgesic medication. A diagnostic injection was used in the ankle (positive) and subtalar joint (negative) in order to recognize origin of pain. Hemilateral avascular necrosis of the talus is rare. There are no prior reported cases of the use of hemi-implants. This case highlights the potential use of a patient-specific three-dimensional printed Ti6Al4V prosthesis presented in a complex scenario.

13.
Nutrients ; 12(2)2020 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-32085628

RESUMEN

Eating disorders (EDs) are increasingly frequent. Their pathophysiology involves disturbance of peptide signaling and the microbiota-gut-brain axis. This study analyzed peptides and corresponding immunoglobulin (Ig) concentrations in groups of ED. In 120 patients with restrictive (R), bulimic (B), and compulsive (C) ED, the plasma concentrations of leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin were analyzed by Milliplex and those of acyl ghrelin (AG), des-acyl ghrelin (DAG), and α-melanocyte-stimulating hormone (α-MSH) by ELISA kits. Immunoglobulin G (in response to an antigen) concentrations were analyzed by ELISA, and their affinity for the respective peptide was measured by surface plasmon resonance. The concentrations of leptin, insulin, GLP-1, and PYY were higher in C patients than in R patients. On the contrary, α-MSH, DAG, and AG concentrations were higher in R than in C patients. After adjustment for body mass index (BMI), differences among peptide concentrations were no longer different. No difference in the concentrations of the IgG was found, but the IgG concentrations were correlated with each other. Although differences of peptide concentrations exist among ED subtypes, they may be due to differences in BMI. Changes in the concentration and/or affinity of several anti-peptide IgG may contribute to the physiopathology of ED or may be related to fat mass.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/inmunología , Inmunoglobulina G/sangre , Péptidos/sangre , Péptidos/inmunología , Índice de Masa Corporal , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Francia , Péptido 1 Similar al Glucagón/sangre , Humanos , Insulina/sangre , Leptina/sangre , Estudios Longitudinales , Masculino , Péptido YY/sangre
14.
Nutrition ; 73: 110714, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32086112

RESUMEN

In obesity or anorexia, changes in body composition and mostly alterations in fat mass distribution are observed. The lymphatic system, which is implicated in fat absorption, might play a major role in the phenotype and development of these pathologies. In this study, two mice animal models were used: the high-fat diet model used for obesity and the activity-based anorexia model for anorexia. Lymphatic system marker levels were measured by reverse transcriptase quantitative polymerase chain reaction on the different parts of the intestine. Moreover, the effects of these models were evaluated on lymphatic fat absorption using lipidic tracer. Using these two models, lymphatic system alterations were observed. Indeed, whether in the obesity or the anorectic model, lymphatic fat absorption modifications were noticed with an increase of this parameter in the anorectic mice and a decrease in obesity. Expression levels of lymphatic markers also were impaired in these models. Both obesity and anorectic models induced lymphatic system alterations mainly in the jejunum and ileum parts of the intestine. These alterations are associated with lipid absorption modifications.


Asunto(s)
Dieta Alta en Grasa , Obesidad , Animales , Composición Corporal , Dieta Alta en Grasa/efectos adversos , Absorción Intestinal , Intestinos , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología
15.
Int J Obes (Lond) ; 44(5): 1041-1051, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31911661

RESUMEN

BACKGROUND/OBJECTIVES: Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. METHODS: The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the "MetaHIT" database. RESULTS: Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia. CONCLUSIONS: H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Hafnia alvei , Probióticos/farmacología , Animales , Apetito/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos
16.
Microorganisms ; 8(1)2019 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-31878078

RESUMEN

Use of new generation probiotics may become an integral part of the prevention and treatment strategies of obesity. The aim of the present study was to test the efficacy of a potential probiotic strain of lactic bacteria Hafnia alvei (H. alvei) HA4597™, in a mouse model of obesity characterized by both hyperphagia and diet-induced adiposity. For this purpose, 10-week-old high-fat-diet (HFD)-fed hyperphagic ob/ob male mice received a daily treatment with 1.4 × 1010 CFU of H. alvei for 38 days. Effects of H. alvei were compared to those of a lipase inhibitor orlistat (80 mg/kg daily) and a vehicle (NaCl 0.9%) in HFD-fed ob/ob mice. A control untreated group of ob/ob mice received the standard diet throughout the experiment. The vehicle-treated HFD group displayed increased food intake, worsening of adiposity, and glycemia. Treatment with H. alvei was accompanied by decreased body weight and fat-mass gain along with reduced food intake to the level of the standard-diet-fed mice. At the end of the experiment, the group treated with H. alvei showed a decrease of glycemia, plasma total cholesterol, and alanine aminotransferase. The orlistat-treated mice showed a lower rate of body weight gain but were hyperphagic and hyperglycemic. These results demonstrate the beneficial anti-obesity and metabolic effects of H. alvei HA4597™ in mice with obesity resulting from hyperphagia and diet-induced adiposity.

17.
Nutrients ; 11(10)2019 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-31635300

RESUMEN

Microbiota contributes to the regulation of eating behavior and might be implicated in the pathophysiology of anorexia nervosa. ClpB (Caseinolytic peptidase B) protein produced mainly by the Enterobacteriaceae family has been identified as a conformational mimetic of α-MSH, which could result in similar anorexigenic effects. The aim of this study was to highlight the role of the microbiome and the ClpB protein in deregulation and self-maintenance of anorexia pathology. Male C57Bl/6 mice were undergone to the ABA (Activity-Based Anorexia) protocol: after 5 days of acclimatization, both ABA and LFA (Limited Food Access) mice had progressively limited access to food until D17. At the end of protocol, the plasma ClpB concentration and Enterobacteriaceae DNA in colonic content were measured. As expected, dietary restriction induced lost weight in LFA and ABA mice. At D10, colonic permeability and plasma concentration of the ClpB protein were significantly increased in LFA and ABA mice vs. controls. At D17, plasma concentration of ClpB was increased in LFA and ABA mice and, it was correlated with proportion of Enterobacteriaceae in the faeces. These abnormally high ClpB concentrations and all associated factors, and therefore might contribute to the initiation and/or perpetuation of anorexia nervosa by interfering with satiety signaling.


Asunto(s)
Proteínas Bacterianas/metabolismo , Endopeptidasa Clp/metabolismo , Privación de Alimentos , Microbioma Gastrointestinal , Animales , Anorexia Nerviosa , ADN Bacteriano/genética , Enterobacteriaceae/genética , Ratones
18.
Transl Psychiatry ; 9(1): 87, 2019 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-30755592

RESUMEN

Melanocortin 4 receptor (MC4R) plays a key role in regulation of appetite activated by its main ligand α-melanocyte-stimulating hormone (α-MSH) in both central and peripheral targets. α-MSH also binds to circulating immunoglobulins (Igs) but the functional significance of such immune complexes (ICs) in MC4R signaling in normal and pathological conditions of altered appetite has remained unknown. To address this question, we analyzed plasma levels, affinity kinetics, and binding epitopes of α-MSH-reactive IgG extracted from plasma samples of female patients with hyperphagic obesity, anorexia nervosa, bulimia nervosa, binge-eating disorder, and healthy controls. Ability of α-MSH/IgG IC to bind and activate human MC4R were studied in vitro and to influence feeding behavior in vivo in rodents. We found that α-MSH-reactive IgG were low in obese but increased in anorectic and bulimic patients and displayed different epitope and kinetics of IC formation. Importantly, while α-MSH/IgG IC from all subjects were binding and activating MC4R, the receptor binding affinity was decreased in obesity. Additionally, α-MSH/IgG IC had lower MC4R-mediated cAMP activation threshold as compared with α-MSH alone in all but not obese subjects. Furthermore, the cellular internalization rate of α-MSH/IgG IC by MC4R-expressing cells was decreased in obese but increased in patients with anorexia nervosa. Moreover, IgG from obese patients prevented central anorexigenic effect of α-MSH. These findings reveal that MC4R is physiologically activated by IC formed by α-MSH/IgG and that different levels and molecular properties of α-MSH-reactive IgG underlie biological activity of such IC relevant to altered appetite in obesity and eating disorders.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/inmunología , Inmunoglobulina G/inmunología , Obesidad/inmunología , Receptor de Melanocortina Tipo 4/inmunología , alfa-MSH/inmunología , Adolescente , Adulto , Animales , AMP Cíclico/metabolismo , Trastornos de Alimentación y de la Ingestión de Alimentos/sangre , Femenino , Células HEK293 , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Obesidad/sangre , Ratas Sprague-Dawley , Transducción de Señal , Adulto Joven
19.
Foot Ankle Int ; 40(5): 586-595, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30688531

RESUMEN

BACKGROUND: Percutaneous surgery is experiencing sustained growth based on third-generation techniques. This cadaveric study was designed with the main goal of exploring the risk of iatrogenic tendon and neurovascular lesions and defining the safe zones in a percutaneous, intra-articular, chevron osteotomy (PeICO) procedure, as well as assessing the accuracy of the osteotomy itself. METHODS: Eight feet from below-knee fresh-frozen specimens were selected. After the procedure, the specimens were dissected, and structures were inspected for damage. RESULTS: The results of the safety measurements were as follows: (1) distance between portal 1 (P1) and the lateral border of the extensor hallucis longus (EHL) tendon: average 17.6 mm (range 12.7-21.3); (2) distance between P1 and the dorsomedial digital nerve (DMDN): average 7.2 mm (range 1.6-10.4); (3) distance between P1 and the metatarsophalangeal joint: average 15.7 mm (range 9.4-20.5); distance between portal 2 (P2), or the osteosynthesis portal, and the metatarsophalangeal joint: average 25.5 mm (range 22-30.4); distance between P2 and the lateral border of the EHL tendon: average 12.7 mm (range 8-16.7); and distance between P2 and the DMDN: average 4.1 mm (range 1.7-8.2). There were no iatrogenic injuries. The osteotomy angulation in the sagittal plane (reproducibility) average was 85.6 degrees. CONCLUSION: There were no iatrogenic injuries on this cadaveric study of PeICO. CLINICAL RELEVANCE: This study will help orthopedic surgeons understand the risks of performing percutaneous surgery by mimicking an accepted open technique (chevron).


Asunto(s)
Hallux Valgus/cirugía , Osteotomía/métodos , Traumatismos de los Nervios Periféricos/prevención & control , Traumatismos de los Tendones/prevención & control , Adulto , Cadáver , Competencia Clínica , Femenino , Humanos , Enfermedad Iatrogénica/prevención & control , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Curr Med Chem ; 26(3): 546-553, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-28982315

RESUMEN

Specific peptide molecules classified as hormones, neuropeptides and cytokines are involved in intercellular signaling regulating various physiological processes in all organs and tissues. This justifies the peptidergic signaling as an attractive pharmacological target. Recently, a protein mimetic of a peptide hormone has been identified in Escherichia coli suggesting the potential use of specific bacterial proteins as a new type of peptide-like drugs. We review the scientific rational and technological approaches leading to the identification of the E. coli caseinolytic protease B (ClpB) homologue protein as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), a melanocortin peptide critically involved in the regulation of energy homeostasis in humans and animals. Theoretical and experimental backgrounds for the validation of bacterial ClpB as a potential drug are discussed based on the known E. coli ClpB amino acid sequence homology with α-MSH. Using in silico analysis, we show that other protein sources containing similar to E. coli ClpB α-MSH-like epitopes with potential biological activity may exist in Enterobacteriaceae and in some Brassicaceae. Thus, the original approach leading to the identification of E. coli ClpB as an α-MSH mimetic protein can be applied for the identification of mimetic proteins of other peptide hormones and development of a new type of peptide-like protein-based drugs.


Asunto(s)
Endopeptidasa Clp/uso terapéutico , Proteínas de Escherichia coli/uso terapéutico , Proteínas de Choque Térmico/uso terapéutico , Hormonas/uso terapéutico , Imitación Molecular , Péptidos/uso terapéutico , Secuencia de Aminoácidos , Animales , Endopeptidasa Clp/química , Metabolismo Energético , Proteínas de Escherichia coli/química , Microbioma Gastrointestinal , Proteínas de Choque Térmico/química , Hormonas/química , Humanos , Péptidos/química , Conformación Proteica
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