Search results for "DISEASE PROGRESSION"
showing 10 items of 835 documents
Influence of age on osteoarthritis progression after anterior cruciate ligament transection in rats.
2013
Abstract The anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) in young rats is widely used to study the pathogenesis of OA and possible treatment approaches. As aging is a key factor in the progression of this condition, it is hypothesized that animals may vary in their responses to ACLT according to their age. The histopathological features of young (2 month-old) and middle-aged (12 month-old) rats in the presence or absence of ACLT were compared. The results indicated that moderate degradative changes can be detected in the knee joints of sham-operated middle-aged rats compared with young animals. After ACLT, cartilage degradation was significantly higher in midd…
Modulation of Cell Cycle Components by Epigenetic and Genetic Events
2005
Cell cycle progression is monitored by surveillance mechanisms, or cell cycle checkpoints, that ensure that initiation of a later event is coupled with the completion of an early cell cycle event. Deregulated proliferation is a characteristic feature of tumor cells. Moreover, defects in many of the molecules that regulate the cell cycle have been implicated in cancer formation and progression. Key among these are p53, the retinoblastoma protein (pRb) and its related proteins, p107 and pRb2/p130, and cdk inhibitors (p15, p16, p18, p19, p21, p27), all of which act to keep the cell cycle from progressing until all repairs to damaged DNA have been completed. The pRb (pRb/p16(INK4a)/cyclin D1) a…
Molecular mechanisms linking neuroinflammation and neurodegeneration in MS.
2013
Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) and one of the leading causes of neurological deficits and disability in young adults in western countries. Current medical treatment mainly influences disease progression via immunomodulatory or immunosuppressive actions. Indeed, MS research has been foremost focused on inflammation in the CNS, but more recent evidence suggests that chronic disability in MS is caused by neurodegeneration. Imaging studies show an early involvement of neurodegeneration as brain atrophy and gray matter lesions can be observed at disease onset. Thus, neuroprotective treatment strategies and the eluc…
Purkinje cell loss and motor coordination defects in profilin1 mutant mice.
2012
Profilin1 is an actin monomer-binding protein, essential for cytoskeletal dynamics. Based on its broad expression in the brain and the localization at excitatory synapses (hippocampal CA3-CA1 synapse, cerebellar parallel fiber (PF)-Purkinje cell (PC) synapse), an important role for profilin1 in brain development and synapse physiology has been postulated. We recently showed normal physiology of hippocampal CA3-CA1 synapses in the absence of profilin1, but impaired glial cell binding and radial migration of cerebellar granule neurons (CGNs). Consequently, brain-specific inactivation of profilin1 by exploiting conditional mutants and Nestin-mediated cre expression resulted in a cerebellar hyp…
Spleen Tyrosine Kinase (SYK) in the Progression of Peritoneal Fibrosis Through Activation of the TGF-β1/Smad3 Signaling Pathway.
2019
BACKGROUND Long-term exposure to hypertonic and high glucose in peritoneal dialysis fluid can result in peritoneal fibrosis. Spleen tyrosine kinase (SYK) has a role in inflammation and fibrosis. This study aimed to investigate the role of SYK in an in vivo rat model of peritoneal fibrosis and in rat peritoneal mesothelial cells (PMCs) in vitro and to investigate the underlying mechanisms. MATERIAL AND METHODS Sprague-Dawley rats (N=24) were randomized into the sham control group (N=6); the peritoneal fibrosis group (N=6) treated with intraperitoneal chlorhexidine digluconate; the SYK inhibitor group (N=6), treated with chlorhexidine digluconate and fostamatinib; and the TGF-s inhibitor grou…
The role of cefditoren in the treatment of lower community-acquired respiratory tract infections (LRTIs): from bacterial eradication to reduced lung …
2014
Lower respiratory tract infections (LRTIs), including pneumonia and acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD), are among the most common diagnoses in both outpatient and inpatient settings. Due to the burden of LRTIs healthcare providers must adopt practices focused on improving outcomes with the aim to reduce treatment failure and antibiotic resistances. Moreover, the role of acute and chronic infection in the pathogenesis of COPD has received considerable attention, since chronic infection can contribute to airways inflammation and COPD progression. This review discusses the role of cefditoren for the treatment of LRTIs, compared with the definition of "appropria…
Verbal learning and memory and their associations with brain morphology and illness course in schizophrenia spectrum psychoses.
2012
The California Verbal Learning Test and structural brain imaging were administered to 57 subjects with schizophrenia spectrum disorders and 94 controls in a general population sample. Cases had lower semantic cluster scores. Poorer verbal memory strategies were associated with longer duration of illness and heavier use of antipsychotic medication. After controlling for duration of illness, sex, and total gray matter, poorer verbal memory was associated with lower gray matter volume in the cingulate cortex, juxtapositional lobule, right superior temporal gyrus, and precuneus. After controlling for use of antipsychotic medication, there was an association between higher serial clustering and …
Clinical relevance of genetic heterogeneity in HCV
2010
Infection by HCV affects an estimated 170 million people worldwide and it represents one of the major causes of liver transplantation and a heavy burden to healthcare systems. As with many other RNA viruses, HCV is characterized by very high levels of genetic variation, which have been associated to differences in disease progression and efficiency of antiviral treatment. Studies show many contradictory results and little consensus on such associations. Nevertheless, some general guidelines translating research results to clinical practice have been postulated. Here, we review the main research results obtained on HCV variation so far and explore the reasons for their lack of congruence und…
An inducible mouse model of colon carcinogenesis for the analysis of sporadic and inflammation-driven tumor progression.
2007
Colorectal cancer is a life-threatening disease that can develop spontaneously or as a complication of inflammatory bowel diseases. Mouse models are essential tools for the preclinical testing of novel therapeutic options in vivo. Here, we provide a highly reliable protocol for an experimental mouse model to study the development of colon cancers. It is based on the mutagenic agent azoxymethane (AOM), which exerts colonotropic carcinogenicity. Repeated intraperitoneal administration of AOM results in the development of spontaneous tumors within 30 weeks. As an alternative option, inflammation-dependent tumor growth can be investigated by combining the administration of AOM with the inflamma…
Early and late clinical landmarks of corneal dystrophies
2020
Abstract Corneal dystrophies (CDs) represent a heterogenous group of genetic diseases (Lisch and Weiss, 2019). The International Committee of Classification of Corneal Dystrophies (IC3D) distinguishes between 22 distinct forms of corneal dystrophy (CD) which are predominantly autosomal dominant, although autosomal recessive and X-chromosomal dominant and recessive patterns do exist. A detailed corneal examination of as many affected family members as possible can show the phenotypic differences of the various generations. There are few publications which describe the different CDs with regard to the early and late phenotypes. According to early and late phenotype, three types of CD are gene…