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1.
Br J Surg ; 105(3): 168-181, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29405276

RESUMEN

BACKGROUND: This study aimed to examine the effect of metabolic surgery on pre-existing and future microvascular complications in patients with type 2 diabetes mellitus (T2DM) in comparison with medical treatment. Although metabolic surgery is the most effective treatment for obese patients with T2DM regarding glycaemic control, it is unclear whether the incidence or severity of microvascular complications is reduced. METHODS: A systematic literature search was performed in MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) with no language restrictions, looking for RCTs, case-control trials and cohort studies that assessed the effect of metabolic surgery on the incidence of microvascular diabetic complications compared with medical treatment as control. The study was registered in the International prospective register of systematic reviews (CRD42016042994). RESULTS: The literature search yielded 1559 articles. Ten studies (3 RCTs, 7 controlled clinical trials) investigating 17 532 patients were included. Metabolic surgery reduced the incidence of microvascular complications (odds ratio 0·26, 95 per cent c.i. 0·16 to 0·42; P < 0·001) compared with medical treatment. Pre-existing diabetic nephropathy was strongly improved by metabolic surgery versus medical treatment (odds ratio 15·41, 1·28 to 185·46; P = 0·03). CONCLUSION: In patients with T2DM, metabolic surgery prevented the development of microvascular complications better than medical treatment . Metabolic surgery improved pre-existing diabetic nephropathy compared with medical treatment.


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/prevención & control , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/terapia , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/etiología , Humanos , Incidencia , Microvasos , Oportunidad Relativa , Resultado del Tratamiento
2.
Arch Orthop Trauma Surg ; 138(4): 527-535, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29372384

RESUMEN

INTRODUCTION: The Kujala score is the most frequently used questionnaire for patellofemoral disorders like pain, instability or osteoarthritis. Unfortunately, we are not aware of a validated German version of the Kujala score. The aim of our study was the translation and linguistic validation of the Kujala score in German-speaking patients with patella instability and the assessment of its measurement characteristics. MATERIALS AND METHODS: The German Kujala score was developed in several steps of translation. In addition to healthy controls, the Kujala German was assessed in consecutive patients undergoing reconstruction of the medial patellofemoral ligament for recurrent patellar dislocations. Pre-op, 6 and 12 months postop the patients completed the Kujala German score, the KOOS, the Lysholm score, a VAS Pain, and the SF-12v2 scores. In addition, there was a Kujala German Score retest preop after a 1-week interval. RESULTS: We found high reliability in terms of internal consistency for the Kujala score (Cronbach's alpha = 0.87). Convergent validity with the KOOS (symptom r = 0.65, pain r = 0.78, ADL r = 0.74, sports/recreation r = 0.84, quality of life r = 0.70), the Lysholm score (r = 0.88) and the SF-12 physical component summary score (r = 0.79) and VAS pain (r = - 0.71) was also very high. Discriminant validity in terms of correlation with the SF-12 mental component summary Score was satisfactory (r = 0.14). CONCLUSIONS: In conclusion, the German version of the Kujala score proved to be a reliable and valid instrument in the setting of a typical patellofemoral disease treated with a standard patellofemoral procedure.


Asunto(s)
Artralgia/fisiopatología , Inestabilidad de la Articulación , Articulación de la Rodilla/fisiopatología , Ligamentos Articulares/fisiopatología , Articulación Patelofemoral/fisiopatología , Humanos , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/fisiopatología , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
3.
Neuroscience ; 387: 28-37, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28942323

RESUMEN

A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.


Asunto(s)
Investigación Biomédica , Neuropatías Diabéticas/complicaciones , Dolor/complicaciones , Animales , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/tratamiento farmacológico , Progresión de la Enfermedad , Humanos
4.
Joints ; 5(2): 59-69, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29114633

RESUMEN

Purpose A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to non-operative treatment, sham surgery or sham arthroscopic partial meniscectomy. These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice. To facilitate the clinical decision-making process, a consensus was developed. This initiative was endorsed by ESSKA. Methods A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years. Congenital lesions, traumatic meniscus tears and degenerative lesions occurring in young patients, especially in athletes, were excluded. The project followed the so-called formal consensus process, involving a steering group, a rating group and a peer-review group. A total of 84 surgeons and scientists from 22 European countries were included in the process. Twenty questions, their associated answers and an algorithm based on extensive literature review and clinical expertise, were proposed. Each question and answer set was graded according to the scientific level of the corresponding literature. Results The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line of treatment for degenerative meniscus lesions. Arthroscopic partial meniscectomy should only be considered after a proper standardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory. Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up, but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies, such as tumours or fractures of the knee. Discussion The present work offers a clear framework for the management of degenerative meniscus lesions, with the aim to balance information extracted from the scientific evidence and clinical expertise. Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms, it cannot be considered as an exact treatment algorithm. It summarises the results of the "ESSKA Meniscus Consensus Project" ( http://www.esska.org/education/projects ) and is the first official European consensus on this topic. The consensus may be updated and refined as more high-quality evidence emerges. Level of Evidence I.

5.
Orthopade ; 46(10): 805-807, 2017 10.
Artículo en Alemán | MEDLINE | ID: mdl-29149367
6.
Orthopade ; 46(10): 808-821, 2017 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-28875226

RESUMEN

BACKGROUND: The treatment of degenerative meniscal lesions has received increased attention since the publication of several Level 1 studies over the last few years. The following review of literature including the consensus statement given by ESSKA reports on the management of patients with degenerative meniscal lesions. MATERIAL AND METHODS: The analysis includes the literature of Level 1 to 4 studies and the statement of the consensus group of ESSKA concerning the surgical or conservative management of these patients. RESULTS: Meniscal lesions cause progression in osteoarthritis. Patients presenting a combination of degenerative meniscal lesion and osteoarthritis show inferior clinical outcome. The average clinical outcome after surgical treatment was 70 points based on the Lysholm score. Level 1 studies show no difference in clinical outcome. However, over 30% of these patients require arthroscopy at the second stage after an interval of 3 to 6 months. Patients presenting a flap tear or complaining about mechanical symptoms show poor outcome after conservative treatment. DISCUSSION: Level 1 studies have focused on very selected patients. These patients do not represent the daily practice of orthopaedic surgeons. The findings of the level 1 studies should, therefore, not be generalized. According to the consensus statement of ESSKA, the treatment of degenerative meniscal lesions should start with conservative management. In the case of persistent symptoms, surgery should be considered after 3 months. In the case of mechanical symptoms, arthroscopy might be indicated earlier. Arthroscopy in advanced osteoarthritic knees is not indicated due to inferior clinical outcome.


Asunto(s)
Meniscos Tibiales , Osteoartritis de la Rodilla/terapia , Osteoartritis/terapia , Conferencias de Consenso como Asunto , Europa (Continente) , Medicina Basada en la Evidencia , Adhesión a Directriz , Osteoartritis/diagnóstico , Osteoartritis de la Rodilla/diagnóstico , Sociedades Médicas , Medicina Deportiva
7.
Orthopade ; 46(10): 831-838, 2017 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-28887704

RESUMEN

BACKGROUND: Meniscal lesions are among the most important musculoskeletal disorders and are the most common indication for knee joint arthroplasty. However, the structural integrity and function is rarely retained, and a loss of tissue results. Thus, there is a huge demand for meniscal replacement options. CURRENT PROCEDURES: Autografts were used in the past but did not fulfill expectations. Meniscus allografts have been developed to be a viable treatment option. However, availability is limited and evidence of a long-term chondroprotective effect scarce. Artificial scaffolds made from either collagen or PCU foam are available, which aid the regeneration of meniscal tissue and are rather intended as a partial replacement with an intact peripheral rim. Those implants thus have a limited spectrum of indication. While they seem to be symptomatically effective, it remains unclear whether they can reduce secondary cartilage damage. Newer developments aim at a permanent replacement of lost meniscal tissue. LIMITATIONS: In summary, there is currently no meniscal replacement available for a broad range of indications and with a solid scientific foundation. Prophylactic use should be limited to cases with a high chance of progression to osteoarthritis, like a lateral total meniscectomy. Otherwise meniscal replacement should be considered in younger, symptomatic patients with mild to moderate secondary changes. Potential causes of the initial meniscal injury like instability or deformities should be carefully assessed and addressed. In many cases, osteotomy might be a viable alternative to meniscus replacement.


Asunto(s)
Meniscectomía , Prótesis e Implantes , Lesiones de Menisco Tibial/cirugía , Aloinjertos , Autoinjertos , Colágeno , Estudios de Seguimiento , Humanos , Cemento de Policarboxilato , Andamios del Tejido , Uretano
8.
Orthopade ; 46(10): 839-845, 2017 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-28831524

RESUMEN

Meniscal roots play an important role in load distribution of the tibiofemoral knee joint. Thus, meniscal root tears are severe injuries of the knee, which significantly expose cartilage to increased stress. Two entities are distinguished: (i) acute root tears that mainly affect the posterolateral root and often occur with ruptures of the anterior cruciate ligament; and (ii) chronic, degenerative root tears that mainly affect the posteromedial root. For diagnosis of both entities, the patient's medical history, a knee examination and especially MRI play key roles. The treatment of choice is in general transtibial fixation of the torn root, which leads to an increased clinical improvement and a decrease of the progression of arthritis.


Asunto(s)
Osteoartritis de la Rodilla/cirugía , Lesiones de Menisco Tibial/cirugía , Lesiones del Ligamento Cruzado Anterior/complicaciones , Lesiones del Ligamento Cruzado Anterior/diagnóstico , Lesiones del Ligamento Cruzado Anterior/fisiopatología , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior , Progresión de la Enfermedad , Humanos , Imagen por Resonancia Magnética , Meniscos Tibiales/cirugía , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/fisiopatología , Factores de Riesgo , Lesiones de Menisco Tibial/diagnóstico , Lesiones de Menisco Tibial/fisiopatología , Soporte de Peso/fisiología
10.
Knee Surg Sports Traumatol Arthrosc ; 25(2): 335-346, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28210788

RESUMEN

PURPOSE: A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscopic partial meniscectomy compared to non-operative treatment, sham surgery or sham arthroscopic partial meniscectomy. These results introduced controversy in the medical community and made clinical decision-making challenging in the daily clinical practice. To facilitate the clinical decision-making process, a consensus was developed. This initiative was endorsed by ESSKA. METHODS: A degenerative meniscus lesion was defined as a lesion occurring without any history of significant acute trauma in a patient older than 35 years. Congenital lesions, traumatic meniscus tears and degenerative lesions occurring in young patients, especially in athletes, were excluded. The project followed the so-called formal consensus process, involving a steering group, a rating group and a peer-review group. A total of 84 surgeons and scientists from 22 European countries were included in the process. Twenty questions, their associated answers and an algorithm based on extensive literature review and clinical expertise, were proposed. Each question and answer set was graded according to the scientific level of the corresponding literature. RESULTS: The main finding was that arthroscopic partial meniscectomy should not be proposed as a first line of treatment for degenerative meniscus lesions. Arthroscopic partial meniscectomy should only be considered after a proper standardised clinical and radiological evaluation and when the response to non-operative management has not been satisfactory. Magnetic resonance imaging of the knee is typically not indicated in the first-line work-up, but knee radiography should be used as an imaging tool to support a diagnosis of osteoarthritis or to detect certain rare pathologies, such as tumours or fractures of the knee. DISCUSSION: The present work offers a clear framework for the management of degenerative meniscus lesions, with the aim to balance information extracted from the scientific evidence and clinical expertise. Because of biases and weaknesses of the current literature and lack of definition of important criteria such as mechanical symptoms, it cannot be considered as an exact treatment algorithm. It summarises the results of the "ESSKA Meniscus Consensus Project" ( http://www.esska.org/education/projects ) and is the first official European consensus on this topic. The consensus may be updated and refined as more high-quality evidence emerges. LEVEL OF EVIDENCE: I.


Asunto(s)
Algoritmos , Artroscopía/métodos , Enfermedades de los Cartílagos/cirugía , Meniscos Tibiales/cirugía , Anciano , Neoplasias Óseas/diagnóstico por imagen , Enfermedades de los Cartílagos/diagnóstico por imagen , Tratamiento Conservador , Europa (Continente) , Fracturas Óseas/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Meniscos Tibiales/diagnóstico por imagen , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Radiografía , Proyectos de Investigación
11.
Bone Joint J ; 98-B(9): 1185-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27587518

RESUMEN

AIMS: It is widely held that most Baker's cysts resolve after treatment of the intra-articular knee pathology. The present study aimed to evaluate the fate of Baker's cysts and their associated symptoms after total knee arthroplasty (TKA). PATIENTS AND METHODS: In this prospective cohort study, 102 patients with (105 were included, however three were lost to follow-up) an MRI-verified Baker's cyst, primary osteoarthritis and scheduled for TKA were included. Ultrasound was performed to evaluate the existence and the gross size of the cyst before and at one year after TKA. Additionally, associated symptoms of Baker's cyst were recorded pre- and post-operatively. RESULTS: After one year, a Baker's cyst was still present in 87 patients (85%). There was a significant reduction in associated symptoms arising from the Baker's cyst before (71%) to after surgery (31%). No patients developed a new Baker's cyst associated symptoms. However, of the 72 patients who had reported Baker's cyst associated symptoms pre-operatively, 32 patients (44%) still complained of such symptoms one year after surgery. CONCLUSION: Baker's cysts had resolved in only a small number of patients (15%) one year after TKA and symptoms from the cysts persisted in 31%. Cite this article: Bone Joint J 2016;98-B:1185-8.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Osteoartritis de la Rodilla/cirugía , Quiste Poplíteo/cirugía , Adulto , Anciano , Artroscopía/métodos , Estudios de Cohortes , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/diagnóstico , Dimensión del Dolor , Quiste Poplíteo/complicaciones , Quiste Poplíteo/diagnóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler
12.
Exp Clin Endocrinol Diabetes ; 123(10): 617-21, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26240957

RESUMEN

Comprehensive diabetes treatment has been shown to reduce quality of life in diabetic patients. However, there is evidence to suggest that group singing can have positive effects on quality of life in various clinical settings. In this randomized controlled pilot study, the effect of singing as a therapy to reduce stress and improve quality of life was investigated in insulin-dependent diabetic patients, undergoing a lifestyle intervention program. Patients from the singing group felt less discontented following treatment. This effect, however, was lost after 3 months. No effect on serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels could be seen when comparing the singing group with the control group, although reduced levels of ACTH and cortisol 3 days after treatment could be found and were still present after 3 months within the group of patients who undertook singing as a therapy. Singing led to an increase in bodyweight, which interestingly had no effect on glucose control or methylglyoxal levels. Therefore, singing during a lifestyle intervention program for insulin-dependent diabetic patients had a short lasting and weak effect on patients' mood without affecting glucose control, but no significant effect on stress related hormones.


Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Canto , Estrés Psicológico/terapia , Adulto , Anciano , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estrés Psicológico/sangre , Estrés Psicológico/fisiopatología , Factores de Tiempo
13.
Exp Clin Endocrinol Diabetes ; 122(6): 341-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24798861

RESUMEN

Current guidelines for the treatment of type 2 diabetes focus on pharmacological treatment of glucose and cardio-vascular risk factors. The aim of this prospective randomized controlled intervention study was to examine the effects of a psychosocial intervention on clinical endpoints and risk factors in patients with type 2 diabetes and early diabetic kidney disease.110 patients were randomized to receive an 8-week mindfulness-based stress reduction (MBSR) training (n = 53) compared to standard care (n = 57). The study was carried out open-labelled and randomization was performed computer-generated in a 1:1 ratio. Primary outcome of the study was the change in urinary albumin excretion (albumin-creatinine-ratio, ACR); secondary outcomes were metabolic parameters, intima media thickness (IMT), psychosocial parameters and cardiovascular events.89 patients (42 in control group and 47 in intervention group) were analysed after 3 years of follow-up. After 1 year, the intervention group showed a reduction of ACR from 44 [16/80] to 39 [20/71] mg/g, while controls increased from 47 [16/120] to 59 [19/128] mg/g (p = 0.05). Parallel to the reduction of stress levels after 1 year, the intervention-group additionally showed reduced catecholamine levels (p < 0.05), improved 24 h-mean arterial (p < 0.05) and maximum systolic blood pressure (p < 0.01), as well as a reduction in IMT (p < 0.01). However, these effects were lost after 2 and 3 years of follow-up.This is the first study to show that a psychosocial intervention improves cardiovascular risk factors in high risk type 2 diabetes patients. Trial-Registration: NCT00263419 http://clinicaltrials.gov/ct2/show/NCT00263419 TRIAL REGISTRATION: clinicaltrials.gov-Identifier: NCT00263419.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Estrés Psicológico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/psicología , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/terapia , Nefropatías Diabéticas/psicología , Nefropatías Diabéticas/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Estrés Psicológico/psicología , Estrés Psicológico/terapia
14.
J Fish Biol ; 84(6): 1820-41, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24814314

RESUMEN

Critical (<30 min) and prolonged (>60 min) swimming speeds in laboratory chambers were determined for larvae of six species of Australian freshwater fishes: trout cod Maccullochella macquariensis, Murray cod Maccullochella peelii, golden perch Macquaria ambigua, silver perch Bidyanus bidyanus, carp gudgeon Hypseleotris spp. and Murray River rainbowfish Melanotaenia fluviatilis. Developmental stage (preflexion, flexion, postflexion and metalarva) better explained swimming ability than did length, size or age (days after hatch). Critical speed increased with larval development, and metalarvae were the fastest swimmers for all species. Maccullochella macquariensis larvae had the highest critical [maximum absolute 46.4 cm s(-1) and 44.6 relative body lengths (L(B)) s(-1)] and prolonged (maximum 15.4 cm s(-1), 15.6 L(B) s(-1)) swimming speeds and B. bidyanus larvae the lowest critical (minimum 0.1 cm s(-1), 0.3 L(B) s(-1)) and prolonged swimming speeds (minimum 1.1 cm s(-1), 1.0 L(B) s(-1)). Prolonged swimming trials determined that the larvae of some species could not swim for 60 min at any speed, whereas the larvae of the best swimming species, M. macquariensis, could swim for 60 min at 44% of the critical speed. The swimming performance of species with precocial life-history strategies, with well-developed larvae at hatch, was comparatively better and potentially had greater ability to influence their dispersal by actively swimming than species with altricial life-history strategies, with poorly developed larvae at hatch.


Asunto(s)
Perciformes/fisiología , Natación , Animales , Australia , Agua Dulce , Larva/fisiología , Modelos Lineales , Especificidad de la Especie
15.
Exp Clin Endocrinol Diabetes ; 122(5): 316-9, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24710646

RESUMEN

The effect of metformin on methylglyoxal (MG) metabolism was studied in a prospective non-randomized 24 weeks trial in patients with type 2 diabetes.Metformin treatment, in addition to life style intervention, significantly reduced morning glucose and HbA1c whilst body weight and BMI were only marginally reduced during the 24 week trial. Treatment significantly reduced both plasma MG and carboxymethyl-lysine (CML), a marker of oxidative stress. The reduction in MG was paralleled by a significant increase in the activity of Glyoxalase 1 (Glo1), the major route of MG detoxification, in peripheral blood mononuclear cells and red blood cells. Multivariate analysis showed that the changes in MG were dependent upon the metformin treatment.This study supports previous findings that metformin can reduce plasma MG in type 2 diabetic patients. However, given the observed increase in Glo1 activity, this reduction is due not only to the scavenging properties of metformin, but the restoration of Glo1 activity.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/análogos & derivados , Piruvaldehído/sangre , Adulto , Femenino , Humanos , Lactoilglutatión Liasa/metabolismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos
16.
Exp Clin Endocrinol Diabetes ; 121(10): 601-6, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24057510

RESUMEN

The established marker for tubular damage, urinary n-acetyl-beta-d-glucosaminidase is significantly increased in type 1 and 2 diabetes patients and is related to albuminuria and other diabetic complications. In this cross sectional study of type 2 diabetes patients with a history of albuminuria, we studied the relationship between excretion of n-acetyl-beta-d-glucosaminidase in urine and diabetic neuropathy.160 type 2 diabetes patients were screened for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy. N-acetyl-beta-d-glucosaminidase excretion was detected in 24 h urine samples.Urinary excretion of n-acetyl-beta-d-glucosaminidase correlated significantly with -glucose control (fasting glucose r=0.18; p=0.04; HbA1c r=0.20; p=0.02) and urine albumin excretion (r=0.22; p=0.01). Binary regression analyses showed that increased urinary n-acetyl-beta-d-glucosaminidase concentration is an independent predictor for presence of clinical symptoms of peripheral neuropathy (OR 1.8 [95%CI 1.2-2.74] and vibration deficiency [OR 1.7; 95% CI 1.2-2.66]. There was also a significant negative association between urinary n-acetyl-beta-d-glucosaminidase and E/I-Ratio (r=-0.21, p<0.02) as well as the 30:15-Ratio (r=-0.24; p<0.01) of heart rate variability. Furthermore, increased n-acetyl-beta-d-glucosaminidase excretion independently predicted cardiovascular autonomic diabetic neuropathy with an OR for decreased E/I-Ratio of 1.7 [95%CI 1.1-2.75]; (p<0.02) and 30:15-Ratio:OR 2.4 [95% CI 1.26-4.45]; (p<0.01).Urinary n-acetyl-beta-d-glucosami-nidase excretion is an independent marker for diabetic peripheral and cardiovascular autonomic neuropathy in type 2 diabetic patients.


Asunto(s)
Acetilglucosaminidasa/orina , Diabetes Mellitus Tipo 2/orina , Neuropatías Diabéticas/orina , Anciano , Albuminuria/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad
17.
Br J Cancer ; 108(3): 570-8, 2013 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-23299527

RESUMEN

BACKGROUND: As metastasis is the prime cause of death from malignancies, there is vibrant interest to discover options for the management of the different mechanistic steps of tumour spreading. Some approved pharmaceuticals exhibit activities against diseases they have not been developed for. In order to discover such activities that might attenuate lymph node metastasis, we investigated 225 drugs, which are approved by the US Food and Drug Administration. METHODS: A three-dimensional cell co-culture assay was utilised measuring tumour cell-induced disintegrations of the lymphendothelial wall through which tumour emboli can intravasate as a limiting step in lymph node metastasis of ductal breast cancer. The disintegrated areas in the lymphendothelial cell (LEC) monolayers were induced by 12(S)-HETE, which is secreted by MCF-7 tumour cell spheroids, and are called 'circular chemorepellent induced defects' (CCIDs). The putative mechanisms by which active drugs prevented the formation of entry gates were investigated by western blotting, NF-κB activity assay and by the determination of 12(S)-HETE synthesis. RESULTS: Acetohexamide, nifedipin, isoxsuprine and proadifen dose dependently inhibited the formation of CCIDs in LEC monolayers and inhibited markers of epithelial-to-mesenchymal-transition and migration. The migration of LECs is a prerequisite of CCID formation, and these drugs either repressed paxillin levels or the activities of myosin light chain 2, or myosin-binding subunit of myosin phosphatase. Isoxsuprine inhibited all three migration markers, and isoxsuprine and acetohexamide suppressed the synthesis of 12(S)-HETE, whereas proadifen and nifedipin inhibited NF-κB activation. Both the signalling pathways independently cause CCID formation. CONCLUSION: The targeting of different mechanisms was most likely the reason for synergistic effects of different drug combinations on the inhibition of CCID formation. Furthermore, the treatment with drug combinations allowed also a several-fold reduction in drug concentrations. These results encourage further screening of approved drugs and their in vivo testing.


Asunto(s)
Acetohexamida/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Endotelio Linfático/efectos de los fármacos , Isoxsuprina/farmacología , Vasos Linfáticos/efectos de los fármacos , Nifedipino/farmacología , Proadifeno/farmacología , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica , Western Blotting , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Adhesión Celular/efectos de los fármacos , Movimiento Celular , Quimiotaxis/efectos de los fármacos , Técnicas de Cocultivo , Sinergismo Farmacológico , Endotelio Linfático/citología , Endotelio Linfático/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Hipoglucemiantes/farmacología , Metástasis Linfática , Vasos Linfáticos/irrigación sanguínea , Vasos Linfáticos/patología , FN-kappa B/antagonistas & inhibidores , FN-kappa B/genética , FN-kappa B/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Esferoides Celulares/metabolismo , Células Tumorales Cultivadas , Vasodilatadores/farmacología
18.
Br J Cancer ; 108(3): 564-9, 2013 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-23093227

RESUMEN

BACKGROUND: Many cancers spread through lymphatic routes, and mechanistic insights of tumour intravasation into the lymphatic vasculature and targets for intervention are limited. The major emphasis of research focuses currently on the molecular biology of tumour cells, while still little is known regarding the contribution of lymphatics. METHODS: Breast cancer cell spheroids attached to lymphendothelial cell (LEC) monolayers were used to investigate the process of intravasation by measuring the areas of 'circular chemorepellent-induced defects' (CCID), which can be considered as entry gates for bulky tumour intravasation. Aspects of tumour cell intravasation were furthermore studied by adhesion assay, and siRNA-mediated knockdown of intracellular adhesion molecule-1 (ICAM-1). Replacing cancer spheroids with the CCID-triggering compound 12(S)-hydroxyeicosatetraenoic acid (HETE) facilitated western blot analyses of Bay11-7082- and baicalein-treated LECs. RESULTS: Binding of LECs to MCF-7 spheroids, which is a prerequisite for CCID formation, was mediated by ICAM-1 expression, and this depended on NF-κB and correlated with the expression of the prometastatic factor S100A4. Simultaneous inhibition of NF-κB with Bay11-7082 and of arachidonate lipoxygenase (ALOX)-15 with baicalein prevented CCID formation additively. CONCLUSION: Two mechanisms contribute to CCID formation: ALOX15 via the generation of 12(S)-HETE by MCF-7 cells, which induces directional migration of LECs, and ICAM-1 in LECs under control of NF-κB, which facilitates adhesion of MCF-7 cells to LECs.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Adhesión Celular/efectos de los fármacos , Endotelio Linfático/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/química , FN-kappa B/antagonistas & inhibidores , Nitrilos/farmacología , Esferoides Celulares/efectos de los fármacos , Sulfonas/farmacología , Western Blotting , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Movimiento Celular , Quimiotaxis/efectos de los fármacos , Endotelio Linfático/citología , Endotelio Linfático/metabolismo , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas
19.
Knee Surg Sports Traumatol Arthrosc ; 20(4): 718-23, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22323098

RESUMEN

PURPOSE: The purposes of the study were to evaluate and to quantify the pivot shift phenomenon by using a small and easy to handle measuring device for pivot shift quantification. METHODS: Twenty patients (forty knees) with primary torn anterior cruciate ligaments (ACL) were tested under anesthesia, graded by the examiner and by the device according to the IKDC classification [normal (0), glide (1), clunk (2), and gross (3)]. For the grading by the device, a femoral and a tibial miniature inertial sensor measured the acceleration and the angular velocities. Three parameters were used for pivot shift identification and quantification: (1) difference between the positive and negative acceleration peak value (a(diff)), (2) the maximum jerk (j(max)), and (3) the standard deviation (SD(a)) of the acceleration. The ratio between the ACL-deficient and the intact knees was calculated in order to normalize the data. RESULTS: The pivot shift phenomenon could be identified, and all three parameters showed significant higher values in the ACL-deficient knees compared to the intact knees (p < 0.05). The grading by examiner did not significantly correlate with a(diff) (p = 0.38; r = 0.21), j(max) (p = 0.36; r = -0.22), SD(a) (p = 0.65; r = 0.11), and grading by the device (p = 0.62; r = 0.12). CONCLUSIONS: The present study has shown that the quantification of the pivot shift test is practicable when inertial sensors are used. The results have shown that the subjective grading of the pivot shift test does not correlate well with objective quantification.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Artrometría Articular/métodos , Inestabilidad de la Articulación/diagnóstico , Rango del Movimiento Articular/fisiología , Aceleración , Adulto , Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/métodos , Estudios de Cohortes , Diseño de Equipo , Estudios de Evaluación como Asunto , Femenino , Humanos , Inestabilidad de la Articulación/cirugía , Traumatismos de la Rodilla/diagnóstico , Traumatismos de la Rodilla/cirugía , Masculino , Examen Físico/métodos , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Adulto Joven
20.
Geobiology ; 10(3): 216-22, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22212713

RESUMEN

This study investigates the role iron oxidation plays in the purple non-sulfur bacterium Rhodobacter capsulatus SB1003. This organism is unable to grow photoautotrophically on unchelated ferrous iron [Fe(II)] despite its ability to oxidize chelated Fe(II). This apparent paradox was partly resolved by the discovery that SB1003 can grow photoheterotrophically on the photochemical breakdown products of certain ferric iron-ligand complexes, yet whether it could concomitantly benefit from the oxidation of Fe(II) to fix CO(2) was unknown. Here, we examine carbon fixation by stable isotope labeling of the inorganic carbon pool in cultures growing phototrophically on acetate with and without Fe(II). We show that R. capsulatus SB1003, an organism formally thought incapable of phototrophic growth on Fe(II), can actually harness the reducing power of this substrate and grow photomixotrophically, deriving carbon both from organic sources and from fixation of inorganic carbon. This suggests the possibility of a wider occurrence of photoferrotrophy than previously assumed.


Asunto(s)
Compuestos Ferrosos/metabolismo , Rhodobacter capsulatus/crecimiento & desarrollo , Rhodobacter capsulatus/metabolismo , Dióxido de Carbono/metabolismo , Procesos Heterotróficos , Oxidación-Reducción , Procesos Fototróficos
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