Dietary protein restriction and preservation of kidney function in chronic kidney disease.

Dietary protein augmentation elicits an increase in single nephron glomerular filtration rate (GFR) and increased transglomerular pressure. This is similar to the hemodynamic response to reduction in renal mass. Among patients and experimental animals with proteinuric renal disease, these changes also cause an increase in glomerular permselectivity, which in experimental animals accelerates loss of renal function. A meta-analysis of a group of prospective randomized trials including over 2,000 patients found a significant effect on reducing dietary protein decreasing the risk of end-stage renal disease or death (defined as renal death). This differs somewhat in the outcomes of clinical trials using intermediate outcomes, such as the Modification of Diet in Renal Disease study that used change in GFR in part because of the initial hemodynamic effect of reduction in GFR mediated by dietary protein restriction.

Safe botulinum toxin type A injection in patients with history of eyelid ptosis.

BACKGROUND: Ptosis is an important side effect of frown correction by botulinum toxin type A (BTX-A). The most likely reason of eyelid ptosis is the diffusion of the toxin to levator palpebrae superioris muscle through orbital septum while the toxin is injected into the corrugator muscle. OBJECTIVES: In this pilot study, to prevent ptosis, we evaluated the efficacy of BTX-A injection at superior middle aspect of the corrugator muscle instead of the common injection site located above the medial eyebrow head. METHODS: Fifteen patients were selected from those referred to our clinic with history of eyelid ptosis due to previous BTX-A (dysport; Ipsen) injection. They received three injections of BTX-A; 10 U into the procerus muscle and 20 U into the superior middle aspect of each corrugator muscle, instead of injecting into the belly of the corrugator muscles. RESULTS: We observed excellent, good and moderate responses in 66.66%, 13.33% and 20% of our patients 2 weeks post-injection respectively. The outcomes were improved to excellent in the latter two groups by injecting 5 U of BTX-A (dysport; Ipsen) into the contractible corrugator in patients with good and 5 U in each corrugator (total of 10 U) in patients with moderate responses. CONCLUSION: Employing this method a very satisfactory outcome was obtained while no ptosis was observed. Therefore, we recommend this safe technique for treating patients with a history of eyelid ptosis.

Raf-1 kinase inhibitor protein: structure, function, regulation of cell signaling, and pivotal role in apoptosis.

The acquisition of resistance to conventional therapies such as radiation and chemotherapeutic drugs remains the major obstacle in the successful treatment of cancer patients. Tumor cells acquire resistance to apoptotic stimuli and it has been demonstrated that conventional therapies exert their cytotoxic activities primarily by inducing apoptosis in the cells. Resistance to radiation and chemotherapeutic drugs has led to the development of immunotherapy and gene therapy approaches with the intent of overcoming resistance to drugs and radiation as well as enhancing the specificity to eliminate tumor cells. However, cytotoxic lymphocytes primarily kill by apoptosis and, therefore, drug-resistant tumor cells may also be cross-resistant to immunotherapy. To evade apoptosis, tumor cells have adopted various mechanisms that interfere with the apoptotic signaling pathways and promote constitutive activation of cellular proliferation and survival pathways. Thus, modifications of the antiapoptotic genes in cancer cells are warranted for the effectiveness of conventional therapies as well as novel immunotherapeutic approaches. Such modifications will avert the resistant phenotype of the tumor cells and will render them susceptible to apoptosis. Current studies, both in vitro and preclinically in vivo, have been aimed at the modification and regulation of expression of apoptosis-related gene products and their activities. A novel protein designated Raf-1 kinase inhibitor protein (RKIP) has been partially characterized. RKIP is a member of the phosphatidylethanolamine-binding protein family. RKIP has been shown to disrupt the Raf-1-MEK1/2 [mitogen-activated protein kinase-ERK (extracellular signal-regulated kinase) kinase-1/2]-ERK1/2 and NF-kappaB signaling pathways, via physical interaction with Raf-1-MEK1/2 and NF-kappaB-inducing kinase or transforming growth factor beta-activated kinase-1, respectively, thereby abrogating the survival and antiapoptotic properties of these signaling pathways. In addition, RKIP has been shown to act as a signal modifier that enhances receptor signaling by inhibiting G protein-coupled receptor kinase-2. By regulating cell signaling, growth, and survival through its expression and activity, RKIP is considered to play a pivotal role in cancer, regulating apoptosis induced by drugs or immune-mediated stimuli. Overexpression of RKIP sensitizes tumor cells to chemotherapeutic drug-induced apoptosis. Also, induction of RKIP by drugs or anti-receptor antibodies sensitizes cancer cells to drug-induced apoptosis. In this review, we discuss the discovery, structure, function, and significance of RKIP in cancer.