Cáncer de riñón hereditario

Kidney cancer is the tenth most common cause of cancer death. There are a growing number of genes known to be associated with an increased risk of specific types of kidney cancer.People with Von Hippel-Lindau syndrome have about a 40% risk of developing multiple bilateral clear cell kidney cancers. They can also develop retinal and brain hemangioblastoma, kidneys or pancreas cysts, pheochromocytoma and endolymphatic sac tumor. Four phenotypes with different renal cancer and pheocromocitoma risk have been described depending on the germline mutation.Hereditary papillary renal cell carcinoma syndrome has type 1 papillary renal cell carcinomas associated with protooncogene c-MET germline mutations.Birt-Hogg-Dubé syndrome has FLCN gene mutations associated with fibrofolliculomas, lung cysts with a high risk for spontaneous pneumothorax, and a 15% to 30% risk of kidney cancer (most classified as chromophobe carcinoma, oncocytoma or oncocytic hybrid, but clear cell and papillary kidney cancers have also been reported). Histopathological findings such as oncocytosis and oncocytic hybrids are very unusual outside the syndrome.Hereditary leiomyomatosis and renal cell cancer syndrome shows mutations of Fumarate hydratase gene and cutaneous leiomyomata in 76% of affected individuals, uterine leiomyomata in 100% of females, and unilateral, solitary, and aggressive papillary renal cancer in 10 to 16% of patients. A specific histopathological change is eosinophilic prominent nucleoli with a perinucleolar halo.Tuberous sclerosis complex is one of the most prevalent (1/5.800) hereditary syndromes where renal disease is the second leading cause of death, associated with angiomyolipomas (70%), renal cysts, oncocytomas or clear cell cancer.     

Antagonism between the metabolic responses induced by epinephrine and piroxicam on isolated rat hepatocytes.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most employed therapeutic agents. They have a wide spectrum of biological effects, some of which are independent of cyclooxygenase inhibition, such as the alterations on the components of signal transduction systems. In particular, previous data from our laboratory suggested an antagonism between epinephrine and piroxicam, one of the most prescribed NSAIDs. Thus, this study deals with the epinephrine-piroxicam antagonism recorded for metabolic responses in isolated rat hepatocytes. The obtained results show that epinephrine stimulates lactate and ethanol consumption, stimulates glucose release from lactate only, and has no effect on cellular triacylglycerides content. Otherwise, in a dose-dependent basis, piroxicam stimulates lactate and ethanol consumption accompanied by an increase in triacylglycerides content, without changes in glucose release by hepatocytes. Piroxicam blocks the epinephrine-induced stimulation of glucose release from lactate, and epinephrine blocks the piroxicam-mediated increase in triacylglycerides content from lactate or ethanol. In contrast, the effects of epinephrine and piroxicam, promoting the consumption of lactate and ethanol, are not antagonized or added after the simultaneous administration of both compounds. This last result is probably related to the ability of both compounds to stimulate oxygen consumption. On isolated rat liver mitochondria, micromolar doses of piroxicam partially uncouple oxidative phosphorylation, and paradoxically stimulates an ATP-dependent mitochondrial function as citrullinogenesis. These results show for first time, on isolated rat hepatocytes, an antagonism between the metabolic responses of epinephrine and piroxicam, at the concentration found in plasma after its therapeutical administration.     

Quality of life for oncology patients during the terminal period. Validation of the HRCA-QL index

AIM: The evolution of performance status, disability, and quality of life (QL) according to the Hebrew Rehabilitation Center for Aged QL (HRCA-QL) index for cancer patients through their terminal period is described. The assessment of HRCA-QL validity and reliability is also described. DESIGN: A total of 200 cancer patients were followed up from the onset of their "terminal phase" until they died. Information on symptoms, performance, disability and QL were collected by patient's oncologists in hospital and by their family practitioners and community nurses when the patient was at home. Health measures were: the HRCA-QL index, Karnofsky performance status (KPS) and the Independence in Activities of Daily Living (IADL) index. RESULTS: The three indices were acceptable for a fair number of patients at the start of the terminal phase. Almost two-thirds had a KPS > or =60. With respect to the IADL index, the patients were independent in five of the six functions, with 80% having a HRCA-QL equal to or greater than 4. The median duration of the terminal period was 59 days. All three indices declined progressively, with marked deterioration in the last 2 weeks. The HRCA-QL index was highly correlated with KPS and the IADL index, had good internal consistency and showed an acceptable test-retest and inter-rater reliability. The HRCA-QL index was reactive to clinical changes. CONCLUSIONS: All three scales confirmed that terminal patients experience a progressive loss of performance, increase in dependence and deterioration of QL as they approach the end of life. Based in these results, we consider the HTCA-QL index valid for use in terminal cancer patients.     

[<Superscript>18</Superscript>F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats

Purpose

Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter.

Procedures

In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism.

Results

The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [¹⁸F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [¹⁸F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p?=?0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session.

Conclusion

Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [¹⁸F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.

     

Mice lacking ghrelin receptors resist the development of diet-induced obesity

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Since its discovery, accumulating evidence has suggested that ghrelin may play a role in signaling and reversing states of energy insufficiency. For example, ghrelin levels rise following food deprivation, and ghrelin administration stimulates feeding and increases body weight and adiposity. However, recent loss-of-function studies have raised questions regarding the physiological significance of ghrelin in regulating these processes. Here, we present results of a study using a novel GHSR-null mouse model, in which ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons. We show that when fed a high-fat diet, both female and male GHSR-null mice eat less food, store less of their consumed calories, preferentially utilize fat as an energy substrate, and accumulate less body weight and adiposity than control mice. Similar effects on body weight and adiposity were also observed in female, but not male, GHSR-null mice fed standard chow. GHSR deletion also affected locomotor activity and levels of glycemia. These findings support the hypothesis that ghrelin-responsive pathways are an important component of coordinated body weight control. Moreover, our data suggest that ghrelin signaling is required for development of the full phenotype of diet-induced obesity.     

The Brain-Lung-Thyroid syndrome (BLTS): A novel deletion in chromosome 14q13.2-q21.1 expands the phenotype to humoral immunodeficiency

Genetic defects of NKX2-1 are classically associated with hypothyroidism, benign chorea and neonatal respiratory distress. The purpose of this study was to identify the genetic pathogenesis of the “NKX2-1 triad” in a 10 year-old female presenting additional features barely described in the disorder. In the neonatal period, she presented with generalized hypotonia and respiratory distress, with later episodes of frequent wheezing. At 3?month-age developmental dysplasia of the hip was diagnosed and at 10?months, primary hypothyroidism was detected and treated. Subsequently, delayed achievement of developmental milestones and then subtle choreic movements of extremities were identified at 2?years of age. Furthermore, delayed teeth eruption and agenesis of some dental pieces, short stature and joint hyperlaxity were also noticed. At 10?years, a poor immune response to polysaccharide antigens and hypogammaglobulinemia, including all IgG subclasses were detected. Surprisingly, no mutations were identified in the complete coding region of NKX2-1 by PCR and Sanger sequencing. MLPA showed a de novo loss of gene dosage in all 3 probes located in NKX2-1 exons. A CGH-array identified a deletion of 3.32?Mb in chromosome 14q13.2-q21.1 containing 20 genes, including NKX2-1, PAX9 and two candidate genes (NFKB1A and PPP2R3C) involved in immune response. The Brain-Lung-Thyroid syndrome (OMIM#610978; ORPHA:209905) associated with other clinical phenotypes should suggest monoallelic deletions of chromosome 14 causing haploinsufficiency of NKX2-1, and other contiguous genes like PAX9 (hypodontia) or other dosage-sensitive genes in the chromosomal vicinity that emerge as candidates for hypogammaglobulinemia, mainly NFKBIA.