Med Sci Sports Exerc 2006 May; 38(5 Suppl): S8 (Read article online)

Wärnberg J, Ruiz JR, Sjöströmo M, Ortega FB, Nova E, Moreno LA, Mesana MI, Hernandez JJ, González-Lamuño D, Marcos A

Wärnberg J, Ruiz JR, Sjöströmo M, Ortega FB, Nova E, Moreno LA, Mesana MI, Hernandez JJ, González-Lamuño D, Marcos A

Inhal Toxicol 2006 Jul; 18(8): 555-68 (Read article online)

Meng QR, Gideon KM, Harbo SJ, Renne RA, Lee MK, Brys AM, Jones R

The purpose of this study was to investigate whether coexposure to lipopolysacchride (LPS) will heighten the inflammatory response and other pulmonary lesions in mice exposed to cigarette smoke, and thus to evaluate the potential use of this LPS-compromised mouse model as a model for chronic obstructive pulmonary disease (COPD) investigation. AKR/J male mice were exposed to HEPA-filtered air (sham control group), cigarette smoke (smoke group), LPS (LPS group), or smoke plus LPS (smoke-LPS group) by nose-only inhalation. Lungs were collected at the end of the 3-wk exposure and processed for microarray analysis. Clustering and network analysis showed decreased heat-shock response and chaperone activity, increased immune and inflammatory response, and increased mitosis in all three exposed groups. Two networks/function modules were exclusively found in the smoke-LPS group, that is, the downregulated muscle development/muscle contraction process and the upregulated reactive oxygen species production process. Notably, the number of genes and function modules/networks associated with inflammation was reduced in the smoke-LPS group compared to the LPS group. The most upregulated gene in the smoke group, MMP12, is a matrix metalloproteinase that preferentially degrades elastin and has been implicated in COPD development. NOXO1, which was upregulated in all three treatment groups, positively regulates the expression of a subunit of NADPH oxidase (NOX1), a major source of reactive oxygen species, and may play an important role in the pathogenesis of COPD. Serum amyloid A1, which is an acute-phase systemic inflammation marker and can be induced by LPS exposure, was significantly upregulated in the LPS and smoke-LPS groups. MARCO, a scavenger receptor expressed in macrophages that may play a significant role in LPS-induced inflammatory response, was upregulated in the LPS group and the smoke-LPS group, but not in the smoke group. In conclusion, gene expression profiling identified genes and function modules that may be related to COPD pathogenesis and may be useful as biomarkers to monitor COPD progression. In addition, an LPS-compromised mouse model showed potential as a useful tool for studying cigarette smoke-associated COPD.

Biometals 2006 Apr; 19(2): 211-5 (Read article online)

Borregaard N, Cowland JB

NGAL (neutrophil gelatinase-associated lipocalin) also known as lcn2 or siderochalin is constitutively expressed in myelocytes and stored in specific granules of neutrophils. It is highly induced in a variety of epithelial cells during inflammation. Analysis of the crystal structure of NGAL expressed in E.coli showed that NGAL has the ability to bind catecholate type siderophores and in this way prevent bacteria from acquisition of siderophore-bound iron. NGAL (or 24p3 as the highly homologous murine orthologue is named) knock out mice have a profound defect in defense against E.coli after intraperitoneal injection. This defect can be mimicked in wild-type mice by providing siderophore iron, which cannot be sequestered by NGAL, testifying to the specific role of NGAL as a siderophore binding protein in innate immunity. Megalin, a scavenger receptor functions as a receptor for NGAL and mediates uptake into endosomes, but other NGAL receptors are likely to exist.

Anesth Analg 2006 Jun; 102(6): 1781-8 (Read article online)

Estebe JP, Legay F, Gentili M, Wodey E, Leduc C, Ecoffey C, Moulinoux JP

Polyamines are thought to be involved in the regulation of numerous metabolic and electrophysiological processes in the nervous system. In this study we evaluated the effect of a synthetic polyamine-deficient diet on pain in a carrageenan (Car)-induced inflammatory rat model. Inflammation was induced with a unilateral subcutaneous injection of Car in a plantar hindpaw in rats fed without (control group) or with (deficiency group) a polyamine-deficient diet. Ipsilateral and contralateral hyperalgesia was evaluated using the Randall-Sellito pressure test. Heart rate changes were also recorded under general anesthesia. Then, the effects of a bupivacaine sciatic nerve block and subcutaneous injection of naloxone or ketamine were evaluated for Car-induced hyperalgesia. Data were analyzed using analysis of variance followed by unpaired Student's t-test (significance P < 0.05). Before Car injection, no significant difference was observed in response to mechanical stimuli between the control and the deficiency groups (n = 114 in pooled data). Car injection induced significant ipsilateral and contralateral hyperalgesia in the control groups, whereas a significant analgesic effect appeared in the deficient groups on both the ipsilateral and contralateral hindpaws. This analgesic effect was confirmed by the electrocardiogram recording that showed a significant increase in heart rate in the control group after Car injection compared with the deficiency group that showed a decrease in heart rate under general anesthesia. Bupivacaine sciatic nerve block had no significant effect on hypoalgesia phenomena induced by polyamine deficiency. Naloxone administration had no effect in the control group but reversed the analgesic effect in the deficiency group. Ketamine administration induced a significant analgesic effect in the control group and partly reversed the analgesic effect in the deficiency group. In conclusion, a synthetic polyamine-deficient diet had a significant general analgesic effect on Car-induced mechanical hyperalgesia. The mechanism of analgesic action remains to be elucidated.

Free Radic Biol Med 2006 Jun 1; 40(11): 1875-1888 (Read article online)

Won JS, Singh I

Sphingolipids including ceramide and its derivatives such as ceramide-1-phosphate, glycosyl-ceramide, and sphinogosine (-1-phosphate) are now recognized as novel intracellular signal mediators for regulation of inflammation, apoptosis, proliferation, and differentiation. One of the important and regulated steps in these events is the generation of these sphingolipids via hydrolysis of sphingomyelin through the action of sphingomyelinases (SMase). Several lines of evidence suggest that reactive oxygen species (ROS; O(2)(-), H(2)O(2), and OH(-),) and reactive nitrogen species (RNS; NO, and ONOO(-)) and cellular redox potential, which is mainly regulated by cellular glutathione (GSH), are tightly linked to the regulation of SMase activation. On the other hand, sphingolipids are also known to play an important role in maintaining cellular redox homeostasis through regulation of NADPH oxidase, mitochondrial integrity, and antioxidant enzymes. Therefore, this paper reviews the relationship between cellular redox and sphingolipid metabolism and its biological significance.

Neurology 2006 May 23; 66(10 Suppl 4): S24-36 (Read article online)

Jenner P, Olanow CW

Concepts of pathogenesis in Parkinson's disease (PD) have been based on attempts to understand the mechanisms responsible for nigral dopaminergic cell death. Pathogenesis has been proposed to involve oxidative and nitrative stress, excitotoxicity, inflammation, mitochondrial dysfunction, and altered proteolysis. These processes are considered to form a complex cascade of interrelated events that lead to neuron death by way of apoptosis. However, current views on pathogenic mechanisms in PD may not be as exact as commonly proposed. Future concepts of pathogenesis in PD need to incorporate events leading to the destruction of non-dopaminergic nuclei and to distinguish between primary factors that are responsible for disease initiation and secondary factors that contribute to disease progression. Importantly, there is a need to determine whether PD is a single illness with a common pathogenesis or a group of related illnesses with different pathogenic mechanisms. This is an essential step to understanding pathogenesis and is critical to the development of comprehensive neuroprotective approaches to treatment.

World J Gastroenterol 2006 May 28; 12(20): 3225-8 (Read article online)

Floch MH, White JA

Diverticular disease of the colon is primarily a disease of humans living in westernized and industrialized countries. Sixty percent of humans living in industrialized countries will develop colonic diverticula. It is rare before the age of 40, but more prone to complications when it occurs in the young. By age 80, over 65% of humans have colonic diverticula. The cause remains uncertain, but epidemiologic studies attribute it to dietary fiber deficiency. The cause of diverticulitis remains uncertain, but new observations and hypotheses suggest that it is due to chronic inflammation in the bowel wall. Standard medical therapies of bowel rest and antibiotics are still the recommended treatment. However, changing concepts and new therapies indicate that anti-inflammatory agents such as mesalamine and possibly probiotics may be helpful in shortening the course and perhaps preventing recurrences. Standard surgical treatment for perforation for severe acute disease has developed so that two-stage procedures are recommended. In addition, laparoscopic surgery has proven safe and may slowly become the technique of choice.

Horm Metab Res 2006 May; 38(5): 346-51 (Read article online)

Kempf K, Haltern G, Füth R, Herder C, Müller-Scholze S, Gülker H, Martin S

Inflammation contributes to the development of atherosclerosis and cardiovascular events. Counteracting pro- and anti-inflammatory responses of serum cytokines have been reported, but the relevance of TNF-alpha, TGF-beta and IL-6 gene expression in peripheral blood leukocytes and their contribution to systemic inflammation in atherosclerosis, especially after acute myocardial infarction (AMI), has not been investigated yet. Using quantitative RT-PCR, we determined temporal cytokine mRNA expression alterations in blood cells from patients with AMI (n = 51). Serum cytokine concentrations were analyzed in parallel using the ELISA technique. TNF-alpha mRNA expression rates and serum concentrations were significantly elevated in AMI patients compared to controls (n = 77), while mRNA expression and serum content of TGF-beta were decreased. Interestingly, we found no statistically significant correlation between transcript and protein levels, indicating that gene expression in leukocytes may be an independent sign for systemic inflammation. While IL-6 was significantly increased in serum from AMI patients with positive correlation to left ventricular dysfunction and negative correlation to ejection fraction, IL-6 mRNA levels did not differ between patients and controls. Gene expression alterations indicate a sophisticated regulation of counteracting TNF-alpha and TGF-beta cytokine expression in peripheral blood leukocytes after AMI with bias towards a pro-inflammatory situation.

Proc Natl Acad Sci U S A 2006 May 22; (Read article online)

Handley SA, Dube PH, Miller VL

Enteric pathogens such as Yersinia enterocolitica readily colonize and induce disease within the lymphatic tissues of the small intestine. To gain a comprehensive view of the host response to pathogens within these tissues, we determined the transcriptional profiles of intestinal lymphatic tissue infected with Y. enterocolitica. Expression analysis using Affymetrix GeneChips revealed a complex host response in the Peyer's patches and mesenteric lymph nodes after oral infection with Y. enterocolitica. Interestingly, histidine decarboxylase (Hdc) was significantly up-regulated in response to Y. enterocolitica infection. HDC is the enzyme solely responsible for the production of the biogenic amine histamine. Although histamine is well known for its role in allergy and for its effects on immunity and inflammation, little is known about its role or specific histamine receptors during the host response to bacterial infection. In this study, we provide evidence that histamine signaling through the histamine H2 but not the H1 receptor is important for controlling Y. enterocolitica infection within the Peyer's patches and mesenteric lymph nodes of mice.

Neurology 2006 May 23; 66(10): 1485-9 (Read article online)

Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG

BACKGROUND: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS). However, some patients with otherwise typical NMO have additional symptoms not attributable to optic nerve or spinal cord inflammation or have MS-like brain MRI lesions. Furthermore, some patients are misclassified as NMO by the authors' earlier proposed criteria despite having a subsequent course indistinguishable from prototypic MS. A serum autoantibody marker, NMO-IgG, is highly specific for NMO. The authors propose revised NMO diagnostic criteria that incorporate NMO-IgG status. METHODS: Using final clinical diagnosis (NMO or MS) as the reference standard, the authors calculated sensitivity and specificity for each criterion and various combinations using a sample of 96 patients with NMO and 33 with MS. The authors used likelihood ratios and logistic regression analysis to develop the most practical and informative diagnostic model. RESULTS: Fourteen patients with NMO (14.6%) had extra-optic-spinal CNS symptoms. NMO-IgG seropositivity was 76% sensitive and 94% specific for NMO. The best diagnostic combination was 99% sensitive and 90% specific for NMO and consisted of at least two of three elements: longitudinally extensive cord lesion, onset brain MRI nondiagnostic for MS, or NMO-IgG seropositivity. CONCLUSIONS: The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity. CNS involvement beyond the optic nerves and spinal cord is compatible with NMO.

Scand J Gastroenterol 2006 Jun; 41(6): 720-5 (Read article online)

Kolho KL, Raivio T, Lindahl H, Savilahti E

Objective. Fecal calprotectin is a promising marker for the assessment of gastrointestinal inflammation. Fecal calprotectin levels were followed-up in children with inflammatory bowel disease (IBD) who were introduced to glucocorticoid therapy. The aim of this study was to assess whether the changes in fecal calprotectin levels reflect therapeutic responses. Material and methods. Fecal calprotectin was measured by enzyme immunoassay in 57 children (mean age 9.8 years, range 0.9-18 years) who underwent colonoscopies (IBD n=31, non-IBD disease n=13, normal n=13) and followed-up in 15 children (mean age 13 years, range 3.6-18 years) who were introduced to glucocorticoid therapy because of active IBD at 0, 2, and 4 weeks and at 4-week intervals until one month after discontinuation of the therapy. Results. Fecal calprotectin was <100 microg/g in 70% of the children with normal findings on colonoscopy or a non-IBD disease. Fecal calprotectin was >100 microg/g in all but one child with active IBD and in 13/15 of those children who were introduced to glucocorticoids by the clinicians. Fecal calprotectin values decreased within 4 weeks in line with clinical improvement in 7 children and normalized in 4/15 children during the follow-up. Fecal calprotectin increased in 5/8 of the non-steroid-dependent children after discontinuation of glucocorticoids. Conclusions. Fecal calprotectin is a sensitive marker for chronic colitis. In active disease treated with glucocorticoids, fecal calprotectin levels declined in line with the clinical improvement but seldom fell within the normal range, which suggests ongoing inflammation in a clinically silent disease. The measurement of fecal calprotectin may provide new tools for the assessment of the level of gut inflammation in children with chronic colitis in the follow-up of clinical responses.

Prostate Cancer Prostatic Dis 2006 May 23; (Read article online)

Kaygısız O, Uğurlu O, Koşan M, Inal G, Oztürk B, Cetinkaya M

We investigated the effect of prostatic inflammation on prostate-specific antigen (PSA) and per cent-free PSA levels changing after antibacterial therapy. We evaluated 48 patients whose PSA levels were between 4 and 10 ng/ml, without any suspicious findings on digital rectal examination, with no infection findings in urine analysis. Prostatic inflammation was assessed with prostatic massage. All the patients were given antibiotic therapy for 3 weeks. Patients were re-evaluated 3 weeks after antibacterial therapy with PSA (free/total) and urinalysis. Ten core biopsies were taken with transrectal ultrasound. No differences were found in terms of age, pre- and post-treatment PSA, and PSA varying between patients with and without inflammation in the prostatic massage. In 18 patients, PSA decreased below 4 ng/ml. Prostate cancer was found in 10.8% of the patients with PSA between 4 and 10 ng/ml and none of the patients with PSA values below 4 ng/ml. We suggest an antibiotic therapy for 3 weeks without regarding inflammation findings when PSA is in the gray zone, for biopsy decision.Prostate Cancer and Prostatic Diseases advance online publication, 23 May 2006; doi:10.1038/sj.pcan.4500885.

Int J Toxicol 2006 May-Jun; 25(3): 171-81 (Read article online)

Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Zaldivar F, Kim RC

Proliferol is an investigational new drug containing lidocaine hydrochloride 0.25%, dextrose 12.5%, glycerin 12.5%, and phenol 1.0% in aqueous solution. Despite extensive previous experience with similar drug solutions administered in humans by intraligamentous injection for chronic musculoskeletal conditions for over 50 years, animal toxicity data are unavailable. A pilot study was conducted to assess acute toxic effects prior to undertaking further assessment of this drug. Test animals were four Sprague-Dawley rats and four Yucatan mini-swine. Rats received injections into lumbar paraspinal muscles, whereas swine received injections into lumbosacral ligaments in an attempt to mirror the method of administration in humans. Two doses were studied equivalent to 1x and 5x the typical human dose. Outcomes measured at 24 h and 14 days included clinical observations, clinical chemistry, hematology, urinalysis, local tolerance, and major organ histopathology. In rats and swine, results from clinical chemistry, hematology, and urinalysis were indicative of acute local inflammation. At the high dose, marked (rats) and moderate (swine) short-term above-normal levels in certain liver enzymes were noted. In rats and swine, local tolerance results were indicative of acute local inflammatory changes in the skin, subcutis, and muscle around the injection sites. In rats and swine, major organ histopathology results did not reveal lesions attributable to the drug and clinical observations were within normal limits. In swine, fibroplasia was noted in deeper muscle tissues after 14 days. Injections of Proliferol in lumbar paraspinal muscles in rats and lumbosacral ligaments in swine elicited a modest acute local inflammatory response with no other indications of local or systemic toxicity.

J Exp Med 2006 May 22; (Read article online)

Hanada T, Kobayashi T, Chinen T, Saeki K, Takaki H, Koga K, Minoda Y, Sanada T, Yoshioka T, Mimata H, Kato S, Yoshimura A

Approximately 20% of human cancers are estimated to develop from chronic inflammation. Recently, the NF-kappaB pathway was shown to play an essential role in promoting inflammation-associated cancer, but the role of the JAK/STAT pathway, another important signaling pathway of proinflammatory cytokines, remains to be investigated. Suppressor of cytokine signaling-1 (SOCS1) acts as an important physiological regulator of cytokine responses, and silencing of the SOCS1 gene by DNA methylation has been found in several human cancers. Here, we demonstrated that SOCS1-deficient mice (SOCS1(-/-)Tg mice), in which SOCS1 expression was restored in T and B cells on a SOCS1(-/-) background, spontaneously developed colorectal carcinomas carrying nuclear beta-catenin accumulation and p53 mutations at 6 months of age. However, interferon (IFN)gamma(-/-)SOCS1(-/-) mice and SOCS1(-/-)Tg mice treated with anti-IFNgamma antibody did not develop such tumors. STAT3 and NF-kappaB activation was evident in SOCS1(-/-)Tg mice, but these were not sufficient for tumor development because these are also activated in IFNgamma(-/-)SOCS1(-/-) mice. However, colons of SOCS1(-/-)Tg mice, but not IFNgamma(-/-)SOCS1(-/-) mice, showed hyperactivation of STAT1, which resulted in the induction of carcinogenesis-related enzymes, cyclooxygenase-2 and inducible nitric oxide synthase. These data strongly suggest that SOCS1 is a unique antioncogene which prevents chronic inflammation-mediated carcinogenesis by regulation of the IFNgamma/STAT1 pathways.

World J Gastroenterol 2006 May 21; 12(19): 3060-4 (Read article online)

Yan Q, Yao X, Dai LC, Zhang GL, Ping JL, He JF, Han CF

AIM: To observe the therapeutic effect of early administration of exogenous Basic fibroblast growth factor (bFGF) on acute edematous pancreatitis (AEP) in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three (n=10): normal control group (group I), AEP group (group II) and AEP with bFGF treatment group (group III). AEP was induced by subcutaneous injection of cerulein (5.5 mug/kg and 7.5 mug/kg) at 1 h interval into rats of groups II and III. Three hours after induction of AEP, 100 mug/kg bFGF was administrated intraperitoneally for 1h to group III rats. For test of DNA synthesis in acinar cells, 5-bromo-2'-deoxyuridine (BrdU) labeling solution was intraperitoneally injected into the rats of groups II and III 24 h after bFGF treatment. The changes in serum amylase, lipase, pancreatic tissue wet/dry ratio were detected. RESULTS: In bFGF treatment group, there was a significant decrease in the volume of serum amylase, lipase and the pancreatic wet/dry weight ratio(1383.0+/-94.6 U/L, 194.0+/-43.6 U/L, 4.32+/-0.32) compared to AEP group (3464+/-223.7 U/L, 456+/-68.7 U/L, 6.89+/-0.47) (P<0.01), and no significant difference was found between bFGF treatment and control group (1289+/-94.0 U/L, 171+/-23.4 U/L, 4.12+/-0.26, P>0.05). The inflammatory changes such as interstitial edema, polymorphonuclear neutrophils (PMNs) and vacuolization were significantly ameliorated compared to AEP group (P<0.01). A small number of BrdU-labeled nuclei were observed in acinar cells of AEP rats (1.8+/-0.3 nuclei/microscopic field, n=10) while diffuse BrdU-labeled nuclei were found in bFGF-treated rats (18.9+/-1.4 nuclei/microscopic field, n=10) (P<0.01). Immunohistochemical study showed increased DNA synthesis in pancreatic acinar cells. CONCLUSION: Early administration of exogenous bFGF has significant therapeutic effect on cerulein-induced acute edematous pancreatitis in rats. Its mechanism is related to the amelioration of inflammation and facilitation of pancreatic regeneration.

Microsc Res Tech 2006 May 22; (Read article online)

Cámara JA, Garrosa M, Gayoso MJ

The authors studied the extent of the different epithelia lining the nasal fossae of the albino rat after neonatal closure of one naris. Newborn pups were anesthetized by hypothermia and the external opening of their right naris cauterized, while littermates served as controls. Animals were sacrificed at 3 months, and the occluded (OCF) and nonoccluded (NOF) fossae of experimental animals as well as both fossae of control animals (CTF) were histologically studied. In both control and experimental animals, nasal fossae were lined by five different types of epithelia: squamous stratified, transitional, metaplastic, respiratory, and olfactory epithelia. It was found that closure of one naris provokes reorganization of the epithelial lining in both the occluded and nonoccluded side. In CTF airflow, physical conditions as well as pollutants and biological agents irritate the epithelial lining, causing squamous metaplasia as well as metaplastic epithelium showing inflammation in rostral levels. In CTF caudal levels, the metaplastic epithelium appears to a lesser degree and the respiratory epithelium prevails, except for the most caudal level where the olfactory epithelium is prevalent. In OCF, the protected environment created prevents the occurrence of metaplastic epithelium, the transitional, respiratory, and olfactory epithelia developing in the corresponding area instead. In NOF, where the airflow is double, the same pattern occurs as in CTF, although metaplastic epithelium values are approximately double, suggesting a clear linear effect. An outstanding feature observed was the increased extent of the olfactory epithelium in OCF regarding NOF, although changes in its morphological structure were not found. Airflow properties, including pressure, coldness, velocity, and turbulence, as well as biological and chemical hazards present in inflow, cause histological reorganization of the nasal epithelium lining during postnatal development. Results prove the need to consider airflow changes in nasal fossae surgery and point to the protective value of naris closure in ENT clinics, supporting it as a treatment of atrophic rhinitis. Microsc. Res. Tech., 2006. (c) 2006 Wiley-Liss, Inc.

Free Radic Biol Med 2006 Jun 1; 40(11): 2018-27 (Read article online)

Al-Assaf S, Navaratnam S, Parsons BJ, Phillips GO

The reactions of the carbonate and dichloride radical anions, CO(3)(-) and Cl(2)(-), with the extracellular matrix glycosaminoglycan hyaluronan (HA) have been studied using the kinetic technique of pulse radiolysis and also by steady-state irradiation combined with gel permeation chromatography/multiangle laser light scattering(gpc/MALLS) to measure the rates of reaction with HA and the yield of HA chain scission, respectively. For comparison, the same measurements were made for the reactions of the free radicals ()OH, Br(2)(-), and N(3)(). The carbonate and dichloride radical anions were found to react relatively quickly with HA (7.0 x 10(5) and 6.9 x 10(6) dm(3) mol(-1) s(-1), respectively) although they are much less reactive than the hydroxyl radical, ()OH. Significant yields (20 and 38%, respectively) of chain scission of HA by these radical anions were also determined from the gpc/MALLS experiments, providing some support for their potential participation in the depolymerization of HA in vivo. These results are compared with data obtained for the other free radicals (hydroxyl, azide radicals, and dibromide radical anions) investigated in this study in order to gain an insight into their mechanism of reaction with HA. Earlier chain scission yields of HA by hydroxyl radicals determined by the authors have also been revised using the gpc/MALLS technique employed in the current study. The yields of 52% (absence of air) and 44% (in air) are much lower than the previous values. In the current study, the effect of oxygen on the yields of HA chain breaks is discussed in terms of the reactivity of HA peroxyl radicals in the presence of superoxide radical anions. The relevance of the results of this study to mechanisms of inflammation is discussed.

World J Urol 2006 May 18; (Read article online)

Azzouzi AR, Fourmarier M, Desgrandchamps F, Ballereau C, Saussine C, Haillot O, Lukacs B, Devonec M, de la Taille A

The usual treatments of benign prostate hyperplasia (BPH) including the alpha-blockers, the inhibitors of the 5-alpha reductase and the phytotherapy drugs allow significant improvements of the lower urinary tracts symptoms (LUTS). However, some patients are not responders or have side effects due to the treatments. Other therapeutic approaches described in the literature are possible in order to alleviate the LUTS. The anti-cholinergic drugs seem to be efficient against the irritating symptoms even if they are supposed to be contra-indicated when there is BPH. Anti-diuretic hormone could be useful to treat nocturia due to diuresis reversal. Inflammation is a part of the underlying mechanisms of BPH and as such the role of the anti-inflammatory drugs has to be revised. Eventually, botulinum toxin is more and more used for patients with neurological bladder and could also have a role in LUTS. If the coming clinical studies on those different treatments confirm the preliminary results, the learning societies in charge of the guidelines would have to update the decision trees by adding these new therapeutic approaches.

Arterioscler Thromb Vasc Biol 2006 May 18; (Read article online)

Zhu XY, Daghini E, Chade AR, Rodriguez-Porcel M, Napoli C, Lerman A, Lerman LO

OBJECTIVE: We tested the hypothesis that in early hypertension (HT), increased oxidative stress leads to myocardial microvascular remodeling. METHODS AND RESULTS: Pigs were studied after a 12-week observation: normal (n=8), untreated renovascular HT (n=8), or HT+chronic antioxidant supplementation (HT+A, n=6). Left ventricular muscle mass (LVMM) and myocardial blood flow (MBF) reserve were determined using electron beam computer tomography (CT), and the spatial density and tortuousity of myocardial microvessels (<500 microm) was then measured in myocardial samples with micro-CT. Myocardial microvascular morphology, oxidative stress, inflammation, and growth factor expression were determined in vitro. HT and HT+A had similarly increased arterial pressure and LVMM, but only HT showed impaired MBF response to adenosine. Compared with normal, HT had increased spatial density of myocardial microvessels, which was preserved in HT+A (111.8+/-7.8, 166.3+/-15.7, and 106.4+/-6.1 vessels per cm(2), respectively). HT also showed microvascular thickening, increased systemic and tissue oxidative stress, inflammation, and expression of vascular endothelial growth factor and its receptor Flk-1, most of which were attenuated by antioxidants. CONCLUSIONS: Myocardial microvascular remodeling in early HT is accompanied by tissue oxidative stress, inflammation, and altered growth factor expression, and attenuated by antioxidant intervention. This study underscores a role of increased oxidative stress in modulating myocardial microvascular architecture in early HT.

Vestn Otorinolaringol 2006; 20-24 (Read article online)

Kirasirova EA, Karimova FS, Kabanov VA, Lafutkina NV, Khamzalieva RB

An algorithm of the treatment of laryngo- tracheal stenosis (LTS) is proposed to raise efficacy of surgical treatment of LTS and to reduce the number of postoperative complications. The algorithm comprises adequate preoperative preparation of the patients including pharmacological prophylaxis of inflammation in the operative zone; effective use of laryngotracheoplasty; prophylaxis of postoperative scarring including reconstruction of created laryngotracheal passage and administration of medicines influencing general and local immunity, tissue metabolism, repair in the region of postoperative inflammation. The efficacy of the algorithm was followed up un 54 (33.7%) patients with laryngostenosis and 106 (66,3%) patients with laryngo-tracheal stenosis. The algorithm application help rehabilitate all the patients with laryngeal stenosis and 92 (86.8%) patients with laryngo-tracheal stenosis.