A Model of Salmonella Colitis with Features of Diarrhea in SLC11A1 Wild-Type Mice

Background: Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1 G169D allele) die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1 G169) with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2 Nramp1 congenic started losing weight 5 days post-infection and they began to die from colitis 10–14 days after infection. A SPI-1 (invA) mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPHdeficient (gp91 phox) mice. However, strain 14028s caused severe colitis and diarrhea in gp91 phox-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis. Conclusions: S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore,

Chondrocytes and Meniscal Fibrochondrocytes Differentially Process Aggrecan During De Novo Extracellular Matrix Assembly

Aggrecan is an extracellular matrix molecule that contributes to the mechanical properties of articular cartilage and meniscal fibrocartilage, but the abundance and processing of aggrecan in these tissues are different. The objective of this study was to compare patterns of aggrecan processing by chondrocytes and meniscal fibrochondrocytes in tissue explants and cell–agarose constructs. The effects of transforming growth factor-beta 1 (TGF-β1) stimulation on aggrecan deposition and processing were examined, and construct mechanical properties were measured. Fibrochondrocytes synthesized and retained less proteoglycans than did chondrocytes in tissue explants and agarose constructs. In chondrocyte constructs, TGF-β1 induced the accumulation of a 120-kDa aggrecan species previously detected in mature bovine cartilage. Fibrochondrocyte-seeded constructs contained high-molecular-weight aggrecan but lacked aggrecanase-generated fragments found in native, immature meniscus. In addition, reflecting the lesser matrix accumulation, fibrochondrocyte constructs had significantly lower compression moduli than did chondrocyte constructs. These cell type–specific differences in aggrecan synthesis, retention, and processing may have implications for the development of functional engineered tissue grafts

Anaerobic exercise: induced changes in serum mineral concentrations

Anaerobic exercise, a non 02 – dependent energy metabolism leads to transient metabolic changes, which are corrected gradually by homestatic mechanism. We investigated in eight male subjects, the effects of anaerobic exercise after a day sedentary activity on serum mineral concentration. There was significant variation in the concentration of serum potassium (F= 4.99,P<0.00)and zinc (F=22.48, P<0.05) on sedentary day. On the other hand, serum magnesium, and calcium were unchanged. Anaerobic exercise induced a significant increase in the serum concentrations of calcium (2.11±0.13 vs2.39 ± 0.12 mmol/L, P<0.05), potassium (4.0± 0.4vs 5.3 ± 0.3 mmol/L,P<0.05), and zinc (12.01± 1.48vs 15.96± 1.60 umol/L,P<0.05). Twelve hours later, magnesium (0.88± 0.05,mmol/L,P<0.05} concentration remained high, potassium and calcium concentrations normalized, while zinc concentrated decreased below the pre-exercise value(9.56± 0.81 umol/L,P<0.05}. Urinary magnesium (4.68± 1.27vs2.60± 0.66 umol/min,P<0.05)and zinc(13.71± 3.77 vs8.58 ± 2.28 nmol/min, p<0.05) increased, while calcium (2.40± 1.14vs 2.33± 1.10 mmo/min, NS), potassium (20.26 ±7.03 vs 24.26 ± 4.82 mmol/min, NS) and the urinary output (0.93±0.38 vs 0.78±0.26ml/min, NS) did not change significantly on the day of exercise compared to the sedentary day. The result presented show clearly that mineral concentration vary greatly within given periods of time and more so after anaerobic exercise