An experimental knee joint effusion does not affect plasma catecholamine concentration in humans

Knee joint effusion causes quadriceps inhibition and is accompanied by increased soleus muscle excitability. In order to reverse the neurological alterations that occur to the musculature following effusion, we need to understand the extent of neural involvement. Ten healthy adults were tested on two occasions; during one session, subjects had their knees injected with saline and in the other admission, they did not. Soleus Hmax, Mmax, plasma epinephrine, and norepinephrine concentrations were obtained at five intervals. Results showed that Hmax increased following the effusion, while norepinephrine and epinephrine levels were not altered. We suggest that the soleus facilitation seen following knee effusion results from stimulation of joint mechanoreceptors and removal of descending spinal and supraspinal inhibition and is not the result of a sympathetic response.     

Two unusual lesions in the nasal cavity of infants--a nasal chondromesenchymal hamartoma and an aneurysmal bone cyst like lesion. More closely related than we think?

Benign reparative lesions in the head and neck region in infants are rare and often difficult to classify on histology. Discussed herein are two rare lesions in infants occurring at identical locations in the nasal cavity with striking histologic similarity but different histologic labels. One was a case of nasal chondromesenchymal hamartoma (NCMH) occurring in a 1-year-old child and the other an aneurysmal bone cyst (ABC) like lesion affecting a 4-month infant. Both these lesions were locally destructive and had nearly similar clinical presentation. Both on immunohistochemistry showed myofibroblastic nature and had similar histology except that the ABC like lesion lacked the cartilage component of the former. In view of great similarity in the two lesions, it was thought that the second lesion might also represent a reparative, non-cartilage-containing counterpart of the former.     

Pheophorbide a is a specific probe for ABCG2 function and inhibition

Pheophorbide a (PhA), a chlorophyll catabolite, was shown to be an ABCG2 substrate based on Abcg2(-/-) knockout mouse studies (J. W. Jonker et al., Proc. Natl. Acad. Sci. USA, 99: 15649-15654, 2002). We developed a functional assay for ABCG2 using PhA and the ABCG2 inhibitor fumitremorgin C. In selected cell lines expressing high levels of P-glycoprotein, multidrug resistance-associated protein 1, or ABCG2, PhA transport was observed only in cells expressing ABCG2. Fumitremorgin C-inhibitable PhA transport was found to correlate with cell surface ABCG2 expression as measured by the anti-ABCG2 antibody 5D3. We found that 100 micro M of the cyclin-dependent kinase inhibitor UCN-01 or 1 micro M of the P-glycoprotein inhibitor tariquidar inhibited ABCG2-mediated PhA transport. In 4-day cytotoxicity assays, ABCG2-mediated resistance to SN-38 and topotecan was abrogated in ABCG2-transfected HEK-293 cells treated with 1 micro M tariquidar, and ABCG2-transfected cells were 6-7-fold resistant to UCN-01. PhA is an ABCG2-specific substrate with potential value in measuring ABCG2 function and expression in clinical samples.     

Symptoms of depression and anxiety (MHI) following acute medical/surgical hospitalization and post-discharge psychiatric diagnoses (DSM) in 839 geriatric US veterans

OBJECTIVE: We addressed the relatively unexplored use of screening scores measuring symptoms of depression and/or anxiety to aid in identifying patients at increased risk for post-discharge DSM-IV Axis I diagnoses. We were unable to find such studies in the literature. METHOD: Elderly veterans without recent psychiatric diagnoses were screened for depression and anxiety symptoms upon admission to acute medical/surgical units using the Mental Health Inventory (MHI). Following discharge, those who had exceeded cut-off scores and had been randomized to UPBEAT Care (Unified Psychogeriatric Biopsychosocial Evaluation and Treatment, a clinical demonstration project) were evaluated for DSM diagnoses. We report on 839 patients, mostly male (96.3%; mean age 69.6 +/- 6.7 years), comparing three groups, i.e. those meeting screening criteria for symptoms of (i) depression only; (ii) anxiety only; and (iii) both depression and anxiety. RESULTS: Despite absence of recent psychiatric history, 58.6% of the 839 patients received a DSM diagnosis post-discharge (21.8% adjustment; 15.4% anxiety; 7.5% mood; and 14.0% other disorders). Patients meeting screening criteria for both depression and anxiety symptoms received a DSM diagnosis more frequently than those meeting criteria for anxiety symptoms only (61.9% vs 49.0%, p = 0.017), but did not differ significantly from those meeting criteria for depressive symptoms only (61.9% vs 56.8%, p = 0.174). Although exceeding the MHI screening cut-off scores for depression, anxiety, or both helped to identify patients with a post-discharge DSM diagnosis, the actual MHI screening scores failed to do so. CONCLUSION: Screening hospitalized medical/surgical patients for symptoms of depression, anxiety, and particularly for the combination thereof, may help identify those with increased risk of subsequent DSM diagnoses, including adjustment disorder.     

A rapid 'one-plate' in vitro test for pyrogens

A rapid, 'one-plate' monocyte-activation test is described for detecting endotoxin and non-endotoxin pyrogens in parenteral medicinal products. The one-plate test offers useful gains over conventional 'two-plate' (cell culture plate+ELISA plate) tests in terms of its limit of detection, robustness, speed and cost. The 'one-plate' test is likely to be applicable to a wide range of products because it allows less time for product interference in the test. The 'one-plate' test utilises pyrogen-free anti-cytokine (interleukin (IL)-6 or tumour necrosis factor alpha (TNFalpha)) antibodies (Ab), coated and stabilised onto (pyrogen-free) 96-well plates. Monocytes/monocytic cells, endotoxin (lipopolysaccharides, LPS) standard or sample and (pyrogen-free) second (labelled) Ab are cultured together (usually for 2-4 h) on the Ab-coated plate and then the plate is washed and the ELISA completed. There is no transfer from one plate to another and no (further) incubations of (released) cytokine with, first, coating Ab and, then, developing Ab since these steps have already taken place during the initial cell culture. The rapid, 'one-plate' test is readily automated. The preferred readout is IL-6, which gives a limit of detection of 0.015 endotoxin units (EU)/ml with peripheral blood mononuclear cell (PBMNC), 0.03 EU/ml with diluted whole blood and 0.05 EU/ml with a monocytic cell line (MONO MAC 6).     

The 'intestinal-renal' arginine biosynthetic axis in the aging rat

It has been suggested that L-arginine availability declines with advanced age, which could contribute to the endothelial dysfunction and decreased nitric oxide (NO) production that are features of aging. L-Arginine is made in the kidney and since the aging kidney develops progressive injury there may be decreased synthesis limiting availability. In this study we investigated the impact of aging on the regulation, at the gene level, of the various enzymes that synthesize L-arginine in the kidney (argininosuccinate synthetase and argininosuccinate lyase) and citrulline, the precursor of L-arginine made in the small intestine (phosphate-dependent glutaminase, carbamyl phosphate synthetase-1 and ornithine transcarbamylase). Studies were in young (3-5 months), middle-aged (11-13 months) and old (18-22 months) male and female Sprague-Dawley rats aged under barrier conditions. The plasma, renal cortical and brain cerebellar levels of L-arginine are unchanged in the old male rat, and expression of the genes involved in renal arginine synthesis and small intestinal citrulline synthesis is unchanged or upregulated with age in both males and females. This study shows that the synthesis of L-arginine is maintained with aging despite developing kidney damage. Therefore, the reduced NO generating capacity that occurs in aging must be due to downstream changes in the NO biosynthesis pathway, such as reduced abundance of NO biosynthetic enzymes.     

Chemopreventive effects of dietary mustard oil on colon tumor development

Fatty acid composition of dietary fat is one of the detrimental factors in colon cancer development. Fats containing omega 6-polyunsaturated fatty acids (e.g. corn oil) enhance and omega 3-polyunsaturated fatty acids (e.g. fish oil) reduce chemically-induced colon cancer in animal studies. The purpose of this study is to investigate the effects of dietary mustard oil (containing omega 3-polyunsaturated fatty acid) on azoxymethane-induced colon cancer in rats and compare with corn and fish oil treated groups. Colon tumor incidence and multiplicity were found to be 90, 75, and 50% and 1.7, 0.8, and 0.4 tumors/rat in corn, fish and mustard oil treated groups respectively. Omega-3 polyunsaturated fatty acid levels were highest in serum and colon microsomal fractions of the fish oil group followed by the mustard oil group. Corn oil group had the highest level of omega 6-polyunsaturated fatty acid levels in serum and colon microsomal fractions. The results indicate that dietary mustard oil is more effective in preventing colon cancer in rats than dietary fish oil.     

p53 mutations in bladder cancer: evidence for exogenous versus endogenous risk factors

Bladder cancer is associated with smoking, occupational exposures, and glutathione S-transferase (GST) M1 and N-acetyltransferase (NAT) 2 polymorphisms that may influence carcinogen metabolism, but somatic p53mutations are often CpG dinucleotide G:C-A:T transitions that can occur spontaneously. We conducted a case-control study to determine whether p53mutation characteristics might distinguish cases with environmental versus endogenous causes. p53exons 4-9 were amplified from 146 bladder tumors by PCR, screened by single-strand conformational polymorphism analysis, and sequenced. Thirty-one cases were p53-positive, and 112 were p53-negative (germ line or silent). G:C-A:T transitions were also subclassified as CpG or non-CpG. Cases and 215 clinic controls were interviewed. GSTM1, NAT1, and NAT2 polymorphisms were assayed from peripheral blood. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic and polytomous regression. Case-control ORs for smoking, occupations, and NAT1*10genotype were similar for p53-positive and p53-negative cases. Associations with GSTM1-null and NAT2-slow genotypes were somewhat stronger for p53-positive [OR, 3.3; CI, 1.4-7.8 (GSTM1 null); OR, 1.8; CI, 0.8-4.0 (NAT2 slow)] than p53-negative cases [OR, 1.5; CI:0.9-2.3 (GSTM1 null); OR, 0.9; CI, 0.6-1.4 (NAT2 slow)]. Smoking was strongly associated with CpG G:C-A:T (OR, 15.3; CI:3.6-65) versus other G:C-A:T (OR, 1.8; CI, 0.3-9.8). NAT2 slow genotypes were also associated with CpG G:C-A:T (OR, 6.2; CI:0.7-52), whereas GSTM1 null was associated with non-CpG G:C-A:T (OR, 7.8; CI, 0.9-65). Associations were not substantially different for case subtypes defined by p53mutation status alone. Estimates for p53 subtypes were imprecise but support in vitro evidence that some CpG G:C-A:T transitions may be caused by smoking and other environmental mutagens.