Carbachol, Norepinephrine, and Hypocapnia Stimulate Phosphatidylinositol Turnover in Rat Tracheal Slices

Background: The intracellular mechanisms involved in the alpha-adrenoceptor- or hyperventilation-induced bronchoconstriction remain unknown. Because there is a direct relationship between phosphatidylinositol (PI) metabolism and airway smooth muscle contraction induced by muscarinic agonists, the authors examined the effects of carbachol (CCh), norepinephrine (NE), and hypocapnia on PI turnover in the airway smooth muscle.

Methods: Rat tracheal slices were incubated in Krebs-Henseleit solution containing LiCl and [sup 3 Hydrogen]myo-inositol in the presence of NE, CCh, or neither. The PCO2 in the solution was 36 plus/minus 3 mmHg (normocapnia), 19 plus/minus 2 mmHg (moderate hypocapnia), or 5 plus/minus 2 mmHg (severe hypocapnia), respectively. [sup 3 Hydrogen]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter.

Results: Basal IP1 formed was greater at severe hypocapnia than at normocapnia. Norepinephrine- and CCh-induced IP1 formation were also greater at hypocapnia than at normocapnia.     

Progressive dendritic changes in aging human cortex

The methods of Golgi have been used in the histological evaluation of brain tissue from ten aged patients with and without evidences of senility. A sequence of changes, identified particularly in third layer pyramids in prefrontal and superior temporal cortex, was seen with variable frequency in all aged brains. The intensity of changes noted appeared more a function of the amount of senile change shown by the patient, than of his calendar age. The sequence of histopathological changes involved increasing swelling and lumpiness in outline of the cell body and proximal dendrites, progressive loss of horizontally oriented dendrite systems, especially the basilar shafts, and eventual loss of apical shafts with cell death. Special significance was attached to the loss of horizontal dendrite masses for two reasons: (i) they have been shown to receive, selectively, synaptic terminals from intracortically derived fiber systems and (ii) their densely intertwined and bundled configurations have been proposed as storage sites for central programs. Preferential loss of this dendrite system seems likely to remove, progressively, the more subtle, modulatory aspects of cortical activity, along with a number of essential output programs coded along their surfaces. Deterioration of psychomotor performance with aging may accordingly be conceived in significant degree as a function of the quality of neuropil as well as of the amount of total nerve cell loss.     

Effect of anticholesterol therapy on soluble ICAM-1 in chronic stroke patients with hyperlipidemia

OBJECTIVE: We examined the effects of drug therapy with pravastatin (P) or bezafibrate (B) and diet (D) therapy on serum lipids and soluble intercellular adhesion molecule-1 (sICAM-1) in hyperlipidemic cerebrovascular disease (CVD) patients in the chronic stage. METHODS: This study included 36 patients (28 with cerebral infarction and hyperlipidemia and eight with cerebral hemorrhage and hyperlipidemia) divided into three groups: Group P (12 patients), Group B (10 patients), and Group D (14 patients). Before and after treatment, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and sICAM-1 levels were measured. RESULTS: In Group P, Group B and Group D, TC levels were decreased by 30% (p < 0.005), 21% (p < 0.01), and 21% (p < 0.001), LDL-C levels were decreased by 38% (p < 0.005), 18% (not significant), and 25% (p < 0.005) and TG levels were decreased by 27% (p < 0.05), 53% (p < 0.005) and 22% (p < 0.05), respectively. sICAM-1 levels were decreased by 20% (p < 0.005) in Group P, but were not decreased in Group B or Group D. There was no correlation between deltaTC and delta sICAM-1 (r = 0.172). CONCLUSION: Administration of pravastatin significantly reduced sICAM-1 levels, independently of its decreasing effect on TC and TG in chronic CVD patients. Pravastatin may exert anti-atherosclerotic activity via two distinct mechanisms.     

Protective Role of Genetic Polymorphism of Heat Shock Protein 70-2 for Gastric Cancer Risk

Background Heat shock protein 70-2 (HSP70-2) has a cytoprotective role in various conditions and also protects the gastric mucosa. Recently, polymorphism of HSP70-2 at position 1267 was suggested to be associated with carcinogenesis. We investigated the association of this polymorphism with the risk of gastric cancer in the present study. Methods We examined 223 patients (159 men and 64 women, mean age 64.8 years) with gastric cancer who underwent gastrointestinal endoscopy at our department. The controls were 200 age-matched patients (140 men and 60 women) without gastric cancer diagnosed by gastrointestinal endoscopy. Genotyping was done by PCR-based restriction fragment length polymorphism analysis, and the PCR products were digested with PstI. The two allelic forms, corresponding to the presence or absence of the PstI site, were designated as the P1 allele and P2 allele, respectively. Logistic regression analysis was performed to calculate an odds ratios (ORs) for differences of HSP70-2 polymorphism between the two groups. Results Among the 223 patients with gastric cancer, 46 (20.6%) had P1/P1, 177 (79.4%) were P1 carriers, and 6 (2.7%) were P2/P2. In the control group, 33 (16.5%) patients had P1/P1 polymorphism, 167 (83.5%) were P1 carriers, and 12 (6.0%) were P2/P2. The OR for gastric cancer of subjects with P2/P2 polymorphism relative to P1 carriers was 0.43 (95% CI = 0.16–1.17) (P = 0.097). Among females, the OR for gastric cancer of subjects with P2/P2 polymorphism relative to P1 carriers was 0.10 (95% CI = 0.012–0.838) (P = 0.014). This polymorphism was also associated with a lower risk of middle third cancer (OR = 0.13; 95% CI = 0.02–1.00). Conclusions P2/P2 polymorphism of HSP70-2 at position 1267 was associated with a lower risk of gastric cancer in females.     

Rapid decrease of anti-β-glucan antibody as an indicator for early diagnosis of carinii pneumonitis and deep mycotic infections following immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis

Deep mycosis (aspergillus pneumonia (AsP)) and carinii pneumonitis (PCP) are complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The objective was to clarify the clinical significance of plasma titer of antibody against β-glucans (anti-BG antibody) as a predictor of complications such as AsP or PCP and the prognosis of patients. Enzyme-linked immunosorbent assay was used to measure the plasma titer of antibodies against β-glucans (BG) from Candida albicans in 22 healthy subjects and 52 patients with various stages of AAV. The mean plasma titer of the anti-BG antibody was 2,677 ± 1,686 U in healthy subjects, 691 ± 522 U in patients with untreated active vasculitis (n = 14), and 547 ± 416 U in patients soon after immunosuppressive treatment (n = 24). Healthy subjects had significantly higher antibody titers than the other two groups (P < 0.05). Repeated measurements over the clinical course of AAV revealed an increase during remission to 1,180 ± 130 U (n = 11), while there was a significant rapid decrease to 369 ± 441 U (P < 0.01) concomitantly with elevation in plasma C-reactive protein and BG levels in patients with AAV that had AsP or PCP infection. Antifungal therapy resulted in a rapid rise of anti-BG antibody titer. Experiments in mice suggested that the anti-BG antibody neutralizes BG. Rapid decrease of the anti-BG antibody titer may be a useful indicator for diagnosis of the presence of AsP or PCP and for estimating the prognosis of patients with these opportunistic infections during immunosuppressive treatment of AAV.     

Is omeprazole or misoprostol superior for improving indomethacin-induced delayed maturation of granulation tissue in rat gastric ulcers?

BACKGROUND AND AIMS: Proton pump inhibitors (PPI) and prostaglandin (PG) preparations are believed to both prevent NSAID-induced gastric ulcers and promote the delayed healing of gastric ulcers by NSAIDs, but it remains unclear which of these drugs is superior. The aim of this study was to clarify which achieved better healing of NSAID-induced gastric ulcers, not only with respect to epithelialization but also repair of the submucosal tissues. METHODS: We used acetic acid to induce gastric ulcers in rats, and compared the changes between a control group, NSAID group, NSAID + PPI group and NSAID + PG group. After removing the stomach of each animal, an ulcer index was calculated and the collagen content and type III collagen content of granulation tissue were measured. We also studied fibroblast dynamics, including proliferation, collagen synthesis, differentiation into myofibroblasts, and apoptosis. RESULTS: Indomethacin prevented re-epithelialization of the ulcers, interfered with fibroblast function, and also delayed the replacement of type III collagen. Omeprazole promoted epithelialization, but could not fully reverse the influence of indomethacin on granulation tissue maturation. A concomitant dose with misoprostolreversed it completely. CONCLUSIONS: From our point of view in this study in the use of experimental ulcers, it was thought that compensation of PG should have priority to gastric acid inhibition in terms of healing of NSAID-induced gastric ulcer.     

Increased Circulating Concentrations of Growth-Related Oncogene (GRO)-α in Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammatory state associated with increased risk of intestinal cancers. The aim of this study is to examine serum concentrations of growth-related oncogene (GRO)-α, a cytokine with inflammatory and growth-regulatory properties, in patients with IBD. We measured serum concentrations of GRO-α in 60 patients with ulcerative colitis, 42 patients with Crohn's disease, 16 patients with other colitides, 12 patients with colorectal cancer, and 40 normal subjects using an enzyme-linked immunosorbent assay. We then analyzed how the cytokine was related to clinical and laboratory variables. Serum GRO-α concentrations in patients with active IBD were significantly higher than those in patients with quiescent disease, which in turn were higher than those in normal controls. Concentrations in patients with active ulcerative colitis were higher than in patients with active Crohn's disease. Analysis of paired serum samples showed a decrease in GRO-α after initiation of therapy. Furthermore, serum GRO-α correlated well with laboratory markers of IBD activity. We conclude that GRO-α may have an important role in development of IBD, and might itself be used as a marker of activity. Manipulation of GRO-α function might prove therapeutically useful.