We screened 19 404 isolates (90% of cases) for ofloxacin resistance and measured

levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. EPZ004777 cell line Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected.

Findings 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, an in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive

disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35 . 78, 95% Cl 4.49-285.30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible AG-120 supplier isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88.96, 19.10-414.29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin.

Interpretation Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.

Funding National Institute for Communicable Diseases

of the National Health Laboratory Service (South Africa), US Agency for International Development FRAX597 research buy Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.”
“After recovery from acute muscle pain even minor subsequent muscle use can initiate recurrence of the same mechanical hyperalgesia months or years after the initial injury. We have recently developed a model of this chronic latent hyperalgesia in the rat. In this study, we have examined the possibility that interleukin-6 (IL-6), an inflammatory mediator produced during acute muscle inflammation, can mediate the production of this chronic latent hyperalgesic state in which subsequent exposure to inflammatory mediators produces a markedly prolonged mechanical hyperalgesia. We now report that i.m. injection of IL-6 produced mechanical hyperalgesia, lasting several hours, that was prevented by intrathecal injection of antisense to glycoprotein 130 (gp130), an IL-6 receptor subunit. Furthermore, following complete recovery from i.m. IL-6-induced hyperalgesia, i.m. prostaglandin E-2 produced a mechanical hyperalgesia that was remarkably prolonged compared with naive controls, indicating the presence of chronic latent hyperalgesia.

Together, these results reveal that baculoviruses replicate and express their late genes at normal levels in the absence of its two different types of RNA tripbosphatases.”
“Many studies have demonstrated that the third variable region (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) is a major determinant of coreceptor tropism. Other regions in the surface gp120 subunit of Env can modulate coreceptor tropism in a manner that is not fully understood. In this study, we evaluated the effect of env R406 determinants outside of V3 on coreceptor usage through the analysis of (i) patient-derived env clones that differ in coreceptor tropism,

(ii) chimeric env sequences, and (iii) site-directed mutants. The introduction of distinct V3 sequences from CXCR4-using clones into an R5-tropic env backbone conferred the inefficient use of CXCR4 in some but not all cases. Conversely, in many cases, X4- and dual-tropic env backbones containing the V3 sequences of R5-tropic clones retained the ability to use CXCR4, suggesting that sequences outside of the V3 see more regions of these CXCR4-using clones were responsible for CXCR4 use. The determinants

of CXCR4 use in a set of dual-tropic env sequences with V3 sequences identical to those of R5-tropic clones mapped to the gp41 transmembrane (TM) subunit. In one case, a single-amino-acid substitution in the fusion peptide of TM was able to confer CXCR4 use; however, TM substitutions associated with CXCR4 use varied among different env sequences. These results Sclareol demonstrate that sequences in TM can modulate coreceptor specificity and that env sequences other than that of V3 may facilitate efficient CXCR4-mediated entry. We hypothesize that the latter plays an important role in the transition from CCR5 to CXCR4 coreceptor use.”
“Control of human immunodeficiency virus type 1 (HIV-1) by HLA-B27-positive subjects has been linked to an immunodominant CD8(+) cytotoxic T-lymphocyte (CTL) response targeting the conserved KK10 epitope (KRWIILGLNK(263-272)) in p24/Gag. Viral escape in KK10 typically occurs

through development of an R(264)K substitution in conjunction with the upstream compensatory mutation S(173)A, and the difficulty of the virus to escape from the immune response against the KK10 epitope until late in infection has been associated with slower clinical progression. Rare alternative escape mutations at R(264) have been observed, but factors dictating the preferential selection of R(264)K remain unclear. Here we illustrate that while all observed R(264) mutations (K, G, Q, and T) reduced peptide binding to HLA-B27 and impaired viral replication, the replicative defects of the alternative mutants were actually less pronounced than those for R(264)K. Importantly, however, none of these mutants replicated as well as an R(264)K variant containing the compensatory mutation S(173)A.

It can be concluded that the activation of nicotinic acetylcholine receptors of the dorsal hippocampus and the basolateral amygdala can potentiate the ethanol response in the CPP paradigm. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Rapid detection of novel swine origin influenza A virus (S-OIV) (H1N1) is crucial for timely implementation of infection control measures. In this study, a haemagglutinin (HA) gene-based real-time

TPCA-1 price nucleic acid sequence-based amplification (NASBA) assay was developed for the specific detection of S-OIV (H1N1). The assay was evaluated and validated by comparing it with existing detection methods for S-OIV (H1N1). Results obtained in a 10-fold dilution series assay demonstrated the analytic sensitivity of the present assay was comparable to that of a commercial S-OIV (H1N1) real-time RT-PCR kit and higher than that of the Centers for Disease Control and Prevention (CDC) TaqMan assay. The actual detection limit of the real-time Torin 1 in vitro NASBA assay was approximately 50 copies per reaction. Compared with reference methods (viral culture,

conventional RT-PCR, and real-time RT-PCR), the sensitivity, specificity, positive predictive value, and negative predictive value of the present assay were all 100%. Overall, the results showed that the real-time NASBA assay could be used for sensitive and specific detection of S-OIV (H1N1). (C) 2009 Elsevier B.V. All rights reserved.”
“Glioblastoma multiforme is the most commonly diagnosed malignant primary brain tumour in adults. Invasive behaviour

is the pathological hallmark of malignant gliomas; consequently, its inhibition has been suggested as a therapeutic strategy. tuclazepam Tumour cell-derived gelatinases (matrix metalloproteinase-2, matrix metalloproteinase-9) can be considered prime factors in glioma invasiveness: their expression correlates with the progression and the degree of malignancy. Thus, broad spectrum matrix metalloproteinase inhibitors (MMP inhibitors) have been included in clinical trials. In the present study, the invasiveness, viability and progression of the human glioma cell line U87MG were investigated following treatment with N-O-isopropyl sulfonamido-based hydroxamates (compounds 1 and 2) as MMP-2 inhibitors used at nanomolar concentration. A standard broad spectrum MMP-inhibitor belonging to the classical tertiary sulfonamido-based hydroxamates family (CGS_27023A) was used too. The compounds 1 and 2 resulted in potent inhibition of cell invasiveness (P<0.0001) without affecting viability. In some clinical trials, the combined therapy of temozolomide (an alkylating agent used in glioma treatment) plus marimastat (a broad spectrum MMP inhibitor) has provided evidence of the importance of MMPs to tumor progression and invasiveness.

Similarly, in the infrequent-frequent difference waves, the frontocentral P3a and parietal LPC (late positive complex) elicited by the HN condition were more negative than those by MN stimuli, which elicited more negative amplitudes than the Neutral condition. This suggests that negative emotions of diverse strength, as induced by negative stimuli of varying valences, are clearly different in their impact on visual novelty processing. Novel stimuli of increased negativity elicited more attentional resources during the early novelty detection, and recruited increased inhibitive Selleckchem MG-132 and evaluative

processing during the later stages of response decision and reaction readiness, relative to novel stimuli of reduced negativity. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“We investigated episodic-like (ELM) and procedural memory (PM) in histamine H1 receptor knockout (H1RKO) mice. In order to relate possible behavioral deficits to neurobiological changes, we examined H1R-KO and wildtype (WT) mice in terms of acetylcholine esterase (AChE) activity in subregions of the hippocampus and

AChE and tyrosine hydroxylase (TH) expression in the striatum. Furthermore, we analyzed acetylcholine (ACh), 5-HT GW2580 concentration and dopamine (DA) levels, including metabolites, in the cerebellum of H1R-KO and WT mice. The homozygous H1R-KO mice showed impaired ELM as compared with the heterozygous H1R-KO and WT mice. The performance of homozygous H1R-KO mice in the ELM task was primarily driven by familiarity-based memory processes. While the homozygous H1R-KO mice performed similar to the heterozygous H1R-KO and WT mice during the acquisition of a PM, as measured with an accelerating rotarod, after a retention interval of 7 days their performance was impaired PKC412 relative to the

heterozygous H1R-KO and WT mice. These findings suggest that, both, ELM and long-term PM are impaired in the homozygous H1R-KO mice. Neurochemical assays revealed that the H1R-KO mice had significantly lower levels of AChE activity in the dentate gyrus (DG) and CA1 subregions of the hippocampus as compared with the WT mice. The homozygous H1 R-KO mice also displayed significantly reduced dihydroxy-phenylacetic acid (DOPAC) levels and a reduced DOPAC/DA ratio in the cerebellum, suggesting that the DA turnover in the cerebellum is decelerated in homozygous H1R-KO mice. In conclusion, homozygous H1R-KO mice display severe long-term memory deficits in, both, ELM and PM, which coincide with changes in AChE activity in the hippocampus as well as DA turnover in the cerebellum. The importance of these findings for Alzheimer’s (AD) and Parkinson’s disease (PD) is discussed. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Elevated nitric oxide (NO) and proton levels in synovial fluid are implicated in joint pathology.

To track the fate of NPs following Rarb2Cre expression, we labeled them with membrane-associated enhanced green fluorescent protein (GFP). In TomatoGFP(+)/Rarb2Cre(+) control mice, NPs differentiated into epithelia

of all nephron segments, except into collecting ducts. In TomatoGFP(+)/Rarb2Cre(+)/Rbpj(f/-) conditional knockout mice, NPs developed into podocytes or distal tubular epithelia, indicating selleck screening library that canonical Notch signals were not required for mesenchymal-to-epithelial transition or for the specification of these nephron segments. Conversely, the few proximal tubules and associated cysts that developed in these mice were derived from the 5-10% of NPs that had failed to express Cre and, therefore, had intact Notch signaling. Thus, our fate mapping studies establish that the profound effect of Notch signaling on nephrogenesis is due to the specification of proximal but not distal tubules or podocytes. Kidney International (2011) 79, 1099-1112; doi:10.1038/ki.2010.553; published online 26 January 2011″
“There are three isoforms of the enzyme nitric oxide

synthase (NOS) in mammals: Etomoxir price endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS). All three isoforms oxidize arginine to citrulline in a reaction producing nitric oxide (NO), which regulates multiple signaling pathways and physiological functions in mammals. Less is known about NOS in fishes, in which the existence of eNOS is controversial. Nevertheless, multiple adjustments occur during cold acclimation of fishes, several of which are known to be mediated by eNOS and NO in mammals, including mitochondrial biogenesis, vasodilation and angiogenesis. We hypothesized that if NOS was present, and NO stimulated these pathways in fishes, then the activity of NOS would increase during cold acclimation. To test this hypothesis, we measured the activity and mRNA levels of NOS in three tissues (liver, oxidative muscle, glycolytic muscle) known to undergo mitochondrial

biogenesis and/or angiogenesis. Measurements were made ICG-001 in vivo in the threespine stickleback. Gasterosteus aculeatus acclimated to either warm (20 degrees C) or cold (8 degrees C) temperature for 9 weeks. Cold-acclimated fish were harvested on days 1-3, and at weeks 1, 4 and 9 at 8 degrees C, while warm-acclimated fish were harvested on day 0 and after 9 weeks at 20 degrees C. Transcript levels of NOS were quantified using quantitative real-time PCR, and NOS activity was measured using a radiochemical assay, which detected the rate of catabolism of (14)C-labeled arginine. Neither NOS activity nor transcripts were detected in oxidative muscle or glycolytic muscle of warm- or cold-acclimated stickleback, although transcript levels of nNOS and NOS activity were detected in brain.

Method. An event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients

(59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated.

Results. Facial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety Gilteritinib concentration and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls.

Conclusions. We suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural selleck inhibitor activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and

may be indicative of a certain cognitive-emotional processing reserve.”
“Background. Previous research reported that childhood adversity predicts juvenile-onset but not adult-onset depression, but studies confounded potentially genuine differences in adversity with differences in the recency with which

adversity was experienced. The current study paper took into account the recency of risk when testing for differences among child-, adolescent- and young adult-onset depressions.

Method. Up to nine waves of data were used per subject from two cohorts of the Great Smoky Mountains Study (GSMS; n=1004), covering children in the community aged 9-16, 19 and 21 years. Youth and one of their parents were interviewed using the Child and Adolescent Psychiatric Assessment (CAPA) between ages 9 and 16; these same youth were interviewed using the Young Adult Psychiatric Assessment (YAPA) at ages Selumetinib 19 and 21. The most common psychosocial risk factors for depression were assessed : poverty, life events, parental psychopathology, maltreatment, and family dysfunction.

Results. Consistent with previous research, most childhood psychosocial risk factors were more strongly associated with child-onset than with adolescent-/adult-onset depression. When potentially genuine risk differences among the depression-onset groups were disentangled from differences due to the recency of risk, child-and young adult-onset depression were no longer different from one another. Adolescent-onset depression was associated with few psychosocial risk factors.

Conclusions.

“
“BACKGROUND: Anterior approaches for thoracolumbar corpectomies IWR-1 nmr can have significant morbidity. Spine surgeons have historically performed their own anterior approaches, but recently access surgeons are being used more frequently.

OBJECTIVE: To evaluate the morbidity rates of approaches performed by an access surgeon and by an approach-trained spinal neurosurgeon.

METHODS: From 2004 to 2008, 46 patients undergoing anterior thoracolumbar corpectomies (levels T2-L5) by the senior author (D.C.) were identified and subdivided into 2 groups based on whether an access surgeon was involved. Nine patients were excluded, leaving 37 patients in the final analysis. Blood loss, operative times, length

of hospital stay, complications, and neurological outcomes were evaluated.

RESULTS: Eighteen patients had anterior spinal access by an approach-trained spinal neurosurgeon, and 19 patients underwent the approach by an access surgeon. Surgeries performed by the spinal neurosurgeon alone were comparable to those performed by an access PLX-4720 ic50 surgeon with respect to operative time, days spent in the hospital, blood loss, complication rates, and improvement in neurological function.

CONCLUSION: There appears to be no increased morbidity of anterior approaches performed by an approach-trained spinal neurosurgeon compared with approaches performed by an access surgeon in terms of operative

time, complication rate, and improvement in neurological function.”
“Purpose: A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular AZD5363 mouse filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy.

Materials and Methods: We assembled a cohort of 1,158 patients from 5 institutions who underwent

partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] x 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations.

Results: Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was – 12% for both equations (p = 0.2).

Since unrestricted neuroplastic modifications of network connectivity will result in a cle-stabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, Selleck Daporinad the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e. high previous activity enhances the threshold for synaptic strengthening and vice

versa. However, the relevance of metaplasticity for actual learning processes has not been tested so far. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, and a reaction time task (RTT) by transcranial direct current stimulation (tDCS). If homeostatic rules apply, excitability-diminishing cathodal tDCS should improve subsequent motor learning, especially if combined with the partial NMDA receptor-agoniSt D-cycloserine, which selectively enhances efficacy CB-839 of active receptors, while excitability-enhancing anodal tDCS should reduce it. Only the results for anodal tDCS, when combined with D-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has a limited influence on implicit sequential

motor learning. (C) 2008 Elsevier Ltd. All rights reserved.”
“Mitochondria are involved in the development of organ failure in critical care diseases. However, the mechanisms underlying mitochondrial dysfunction are not clear yet. Inducible hemoxygenase

(HO-1), a member of the heat shock protein family, is upregulated in critical care diseases and considered to confer cytoprotection against oxidative stress. However, one of the products of HO-1 is Fe2+ which multiplies the damaging potential of reactive oxygen species catalyzing Fenton reaction. The aim of this study was to clarify the relevance of free iron metabolism to the oxidative damage of the liver in endotoxic shock and its impact on mitochondrial function. Endotoxic shock in rats was induced by injection of lipopolysaccharide (LPS) at a dose of 8 mg/kg (i.v.). We observed that the pro-inflammatory cytokine TNF-alpha Selleck PD-1/PD-L1 Inhibitor 3 and the liver necrosis marker aspartate aminotransferase were increased in blood, confirming inflammatory response to LPS and damage to liver tissue, respectively. The levels of free iron in the liver were significantly increased at 4 and 8 h after onset of endotoxic shock, which did not coincide with the decrease of transferrin iron levels in the blood, but rather with expression of the inducible form of heme oxygenase (HO-1). The proteins important for sequestering free iron ( ferritin) and the export of iron out of the cells ( ferroportin) were downregulated facilitating the accumulation of free iron in cells.

It is important that future studies carefully consider the criteria

for inclusion.”
“Rationale Long-term heavy cannabis use can result in memory impairment. Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis.

Objectives and methods In a cross-sectional and prospective neuropsychological study of 181 adolescents aged 16-20 (mean 18.3 years), we compared performance indices from one of the most widely used measures Nepicastat mouse of learning and memory-the Rey Auditory Verbal Learning Test-between cannabis users (n=52; mean 2.4 years of use, 14 days/month, median abstinence 20.3 h), alcohol users (n=67) and non-user controls (n=62) matched for age, education and premorbid intellectual ability (assessed prospectively), and alcohol PD173074 in vivo consumption for cannabis and alcohol users.

Results Cannabis users performed significantly worse than alcohol users and non-users on all performance indices. They recalled significantly fewer words overall (p<0.001), demonstrating impaired learning (p<0.001), retention (p<0.001) and retrieval (p<0.05) (Cohen’s d 0.43-0.84). The

degree of impairment was associated with the duration, quantity, frequency and age of onset of cannabis use, but was unrelated to alcohol exposure or other drug use. No gender effects were detected and the findings remained after controlling for premorbid intellectual ability. An earlier age of onset of regular cannabis use was associated with worse memory performance after controlling for extent of exposure to cannabis.

Conclusions Despite relatively brief exposure, adolescent

cannabis users relative to their age-matched counterparts demonstrated similar memory deficits to those reported in adult long-term heavy users. The results indicate that cannabis adversely affects the developing brain and reinforce concerns regarding the impact of early exposure.”
“Background Rheumatoid arthritis is a heterogeneous chronic disease, and no therapeutic agent has been identified which is universally and persistently effective in all patients. We investigated the effectiveness of tofacitinib (CP-690,550), a novel oral Janus kinase inhibitor, as a targeted immunomodulator and disease-modifying therapy Cepharanthine for rheumatoid arthritis.

Methods We did a 6-month, double-blind, parallel-group phase 3 study at 82 centres in 13 countries, including North America, Europe, and Latin America. 399 patients aged 18 years or older with moderate-to-severe rheumatoid arthritis and inadequate response to tumour necrosis factor inhibitors (TNFi) were randomly assigned in a 2: 2: 1: 1 ratio with an automated internet or telephone system to receive twice a day treatment with: tofacitinib 5 mg (n=133); tofacitinib 10 mg (n=134); or placebo (n=132), all with methotrexate.

Results: The radiotracer 1 was readily prepared and purified (from 2: LDC000067 40+/-4 min including HPLC, 11.9+/-3.2% decay corrected isolated radiochemical yield, >99% radiochemical purity, n = 4) and displayed good stability (1 h: >99%, saline; 94.6%, serum). Strong alpha(v)beta(6)-targeted binding was observed in vitro (DX3puro beta 6 cells, 15 min: 43.2% binding, >6:1 for DX3puro beta 6:DX3puro). In the

mouse model DX3puro beta 6-tumor binding was low (1 h: 0.47+/-0.28% ID/g, 4 h: 0.14+/-0.09% ID/g) and clearing from the bloodstream was via the renal and hepatobiliary routes (urine: 167+/-84% ID/g at 1 h, 10.3+/-4.8% ID/g at 4 h; gall bladder: 95+/-33% ID/g at 1 h, 63+/-11% ID/g at 4 h).

Conclusion: Copper-free, strain-promoted click chemistry is an attractive, straightforward approach to radiolabeling. Although the [F-18]FBA-C-6-ADBIO-based Roscovitine mw prosthetic group did not interfere with alpha(v)beta(6)-targeted binding in vitro, it did influence the pharmacokinetics, possibly due to its size and lipophilic nature. (C) 2013 Elsevier

Inc. All rights reserved.”
“Purpose: We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates.

Materials and Methods: Conventional intracellular microelectrode and tension recording techniques were used.

Results: The nitric oxide donor sodium nitroprusside (10 mu M) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 mu M) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly Lormetazepam larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA

p < 0.01). Other measured parameters, including the duration, amplitude and membrane potential of spontaneous electrical and contractile activity, were not altered from control values. The guanylate cyclase inhibitor ODQ (10 mu M) significantly increased the frequency of spontaneous activity by 10% to 30% in 6 young guinea pig prostates (Student paired t test p < 0.05). However, it had no effect on aging prostates. The cGMP analogue 8-Br-GMP (1 mu M) and the PDE5 inhibitor dipyridamole (1 mu M) significantly decreased the frequency of contractile activity by about 70% in 4 to 9 young and older prostates (Student paired t test p < 0.05).

Conclusions: The decrease in the response to L-NAME in spontaneous contractile and slow wave activity in aging prostate tissue compared to that in young prostates suggests that with age there is a decrease in nitric oxide production. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia.