Study protocol: High-protein nutritional intervention based on ß-hydroxy-ß-methylbutirate, vitamin D3 and calcium on obese and lean aged patients with hip fractures and sarcopenia. The HIPERPROT-GER study.

INTRODUCTION: Loss of muscle strength is associated with falls, which, in turn, are the main cause of hip fractures in elderly people. The factors that most influence loss of strength in elderly people are a decrease in muscle mass, i.e. sarcopenia, and an increase in fat, i.e. obesity. METHODS: A prospective randomized clinical trial among patients who have undergone an operation for a traumatic hip fracture and who are aged 65 or above will be implemented. We shall compare a control diet against a high-protein diet enriched with ß-hydroxy-ßmethylbutirate, calcium and vitamin D. The diet will be administered during 30 days of hospitalization in the orthopaedic geriatric rehabilitation unit. There will be 50 patients in each arm of the study. The main objective is to assess whether the experimental diet, together with rehabilitation, improves functional recovery, measured on the Barthel index. Secondary objectives are to assess changes in body composition and the prevalence of sarcopenia, obesity and mortality one year after the hip fracture. We shall also assess whether there is a relationship between specific inflammatory markers, sarcopenia and functional recovery. CONCLUSIONS: Ageing is accompanied by changes in body composition that increase the risk of falls and progressive functional loss. These factors are a public health problem because they are highly associated with disability in older people. The present study seeks to gain knowledge of those factors that are most often associated with the onset of disability and those that can be modified through diet.

The anorexia of ageing: physiopathology, prevalence, associated comorbidity and mortality. A systematic review.

The physiological processes of ageing and factors prevalent in the elderly such as comorbidities and polypharmacy often cause loss of appetite in the elderly, which we call anorexia of ageing. Social factors, together with changes in the sensory organs, can be important causes of a reduction in both appetite and ingestion. This review assesses the regulation of appetite in the elderly and the development of anorexia of ageing. It also examines the prevalence of this type of anorexia, its associated comorbidities and mortality rates. We have reviewed 27 studies, with a total of 6208 patients. These reported changes in the secretion and response of both central and peripheral hormones that regulate appetite. Anorexia, very prevalent among hospitalized and institutionalized elderly people, is associated with comorbidity and represents a predictive factor for mortality. No treatment for it has been proved to be effective. The mechanism regulating ingestion in elderly people is complex and difficult to resolve. Comorbidity as a cause or a consequence of anorexia of ageing has become a research field of great interest in geriatrics. A correct nutritional evaluation is a fundamental part of an integrated geriatric assessment.

Effectiveness of nutritional supplementation on muscle mass in treatment of sarcopenia in old age: a systematic review.

BACKGROUND: Much interest has been focused on nutritional treatment of sarcopenia, loss of muscle mass and performance associated to aging; however, its benefits are unclear. OBJECTIVE: To analyze the relevance of nutritional treatment of sarcopenia and assess the effects of supplementation on muscle mass and function within the aged population. METHODS: We searched Medline and the Cochrane Library for controlled trials published between 1991 and 2012. We have assessed the quality, type of intervention, the cohort used, the way muscle mass was measured, and the outcomes of the various studies. RESULTS: We have included 17 studies, with a total of 1287 patients, aged between 65 and 85 on average. An improvement in muscle mass was proven, whether measured with bioelectrical impedance analysis or dual energy x-ray absorptiometry, and an improvement in strength was also proven. CONCLUSION: Nutritional supplementation is effective in the treatment of sarcopenia in old age, and its positive effects increase when associated with physical exercise. The main limitation of this treatment is lack of long-term adherence. A healthy diet associated with a physically active lifestyle and possibly with aerobic exercise are the basis of healthy aging, which is the aim of all doctors treating aged people must seek.

Sarcopenia in the elderly: diagnosis, physiopathology and treatment.

Sarcopenia, defined as a syndrome rather than as a pathology, is the loss of muscle mass and function associated with age. Sarcopenia is an enigma for medicine, and despite the numerous publications available in the literature and the number of papers currently being published, there is no agreement about its definition, and even less about its root causes. One salient aspect that proves the lack of consensus is the fact that different working groups are still debating about the right name for this syndrome (which is associated with the loss of muscle mass and strength in the elderly). In hospitalized patients, sarcopenia has been shown to raise the risk of complications such as infections, pressure ulcers, loss of autonomy, institutionalization and poor quality of life, as well as to increase mortality. The factors that contribute to the development of sarcopenia in the elderly are: the state of chronic inflammation, atrophy of motoneurons, reduced protein intake (secondary among others to the condition defined as geriatric anorexia), and immobility. There is ongoing debate about the causes of sarcopenia, but the aspect that generates most interest today is the quest to achieve repeatable and clinically useful diagnostic criteria for its diagnosis, prevention and treatment. The aim of this narrative review is to summarise the abundant information available in the literature and to draw useful conclusions.

In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta1.

Down-regulation of CD4+CD25+ regulatory T (Treg) cell function might be beneficial to enhance the immunogenicity of viral and tumor vaccines or to induce breakdown of immunotolerance. Although the mechanism of suppression used by Treg cells remains controversial, it has been postulated that TGF-beta1 mediates their immunosuppressive activity. In this study, we show that P17, a short synthetic peptide that inhibits TGF-beta1 and TGF-beta2 developed in our laboratory, is able to inhibit Treg activity in vitro and in vivo. In vitro studies demonstrate that P17 inhibits murine and human Treg-induced unresponsiveness of effector T cells to anti-CD3 stimulation, in an MLR or to a specific Ag. Moreover, administration of P17 to mice immunized with peptide vaccines containing tumor or viral Ags enhanced anti-vaccine immune responses and improved protective immunogenicity against tumor growth or viral infection or replication. When CD4+ T cells purified from OT-II transgenic mice were transferred into C57BL/6 mice bearing s.c. EG.7-OVA tumors, administration of P17 improved their proliferation, reduced the number of CD4+Foxp3+ T cells, and inhibited tumor growth. Also, P17 prevented development of immunotolerance induced by oral administration of OVA by genetically modified Lactococcus lactis in DO11.10 transgenic mice sensitized by s.c. injection of OVA. These findings demonstrate that peptide inhibitors of TGF-beta may be a valuable tool to enhance vaccination efficacy and to break tolerance against pathogens or tumor Ags.

Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection.

Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by CTLA-4-expressing T cells and constitutes an important mediator of peripheral immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication expressed higher levels of IDO mRNA than noninfected cells when stimulated with gamma interferon or when cocultured with activated T cells. In infected chimpanzees, hepatic IDO expression decreased in animals that cured the infection, while it remained high in those that progressed to chronicity. For both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated directly. Induction of IDO may dampen T-cell reactivity to viral antigens in chronic HCV infection.

[New therapies for hepatitis C]. / Nuevos tratamientos para la hepatitis C.

Hepatitis C virus is an important public health threat, not only because of the high prevalence of this infection in western and third world countries, but also because of the high rate of resistance to the available antiviral therapy that consists on the use of pegylated interferon plus ribavirin. Currently, new forms of therapy are being developed based on a more precise knowledge of the structure and function of the viral proteins and of the strategies used by the virus to escape the immune and interferon systems. The new therapeutic approaches aim at different objectives: a) the inhibition of viral replication by blocking the viral protease and/or replicase; b) the use of other types of interferon with more potent antiviral effect, c) the induction of a specific anti-viral immune response by means of immunomodulatory compounds or therapeutic vaccination, d) the blockade of "de novo" infection of other cells with neutralizing antibodies, e) the induction of a antiviral state in the liver by transferring to this organ the gene of interferon and/or immunostimulating cytokines.

Nuevos tratamientos para la hepatitis C / New therapies for hepatitis C

La infección por el virus de la hepatitis C constituye un importante problema de salud pública, no sólo por su alta prevalencia en muchos países occidentales y del tercer mundo, sino también por la alta tasa de resistencia al tratamiento antivírico hoy disponible consistente en el uso de interferón pegilado y ribavirina. En la actualidad se están desarrollando nuevas formas de tratamiento fundadas en el conocimiento de la estructura y función de las proteínas del virus y de los mecanismos de los que se vale el agente infeccioso para evadir la respuesta inmune e interferónica. Estos nuevos enfoques terapéuticos apuntan a objetivos diversos: a) la inhibición de la replicación vírica con bloqueantes de la proteasa y/o de la replicasa del virus, b) la utilización de tipos de interferón con más potencia antivírica, c) la inducción de respuesta inmune específica antivírica mediante el uso de agentes inmunomoduladores o vacunación terapéutica, d) el bloqueo de la infección "de novo" de otras células con anticuerpos neutralizantes, e) la inducción de un estado antivírico en el hígado utilizando estrategias de transferencia génica del gen del interferón o de citocinas inmuno-estimuladoras

Hepatitis C virus is an important public health threat, not only because of the high prevalence of this infection in western and third world countries, but also because of the high rate of resistance to the available antiviral therapy that consists on the use of pegylated interferon plus ribavirin. Currently, new forms of therapy are being developed based on a more precise knowledge of the structure and function of the viral proteins and of the strategies used by the virus to escape the immune and interferon systems. The new therapeutic approaches aim at different objectives: a) the inhibition of viral replication by blocking the viral protease and/or replicase; b) the use of other types of interferon with more potent antiviral effect, c) the induction of a specific anti-viral immune response by means of immunomodulatory compounds or therapeutic vaccination, d) the blockade of "de novo" infection of other cells with neutralizing antibodies, e) the induction of a antiviral state in the liver by transferring to this organ the gene of interferon and/or immunostimulating cytokines