Stroke unit admission is associated with better outcome and lower mortality in patients with intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There is no clear consensus among current guidelines on the preferred admission ward [i.e. intensive care unit (ICU) or stroke unit (SU)] for patients with intracerebral hemorrhage. Based on expert opinion, the American Heart Association and European Stroke Organization recommend treatment in neurological/neuroscience ICUs (NICUs) or SUs. The European Stroke Organization guideline states that there are no studies available directly comparing outcomes between ICUs and SUs. METHODS: We performed an observational study comparing outcomes of 10 811 consecutive non-comatose patients with intracerebral hemorrhage according to admission ward [ICUs, SUs and normal wards (NWs)]. Primary outcomes were the modified Rankin Scale score at discharge and intrahospital mortality. An additional analysis compared NICUs with SUs. RESULTS: Treatment outside an SU was associated with higher odds for an unfavorable outcome [ICU vs. SU: odds ratio (OR), 1.27; 95% confidence interval (CI), 1.09-1.46; NW vs. SU: OR, 1.28; 95% CI, 1.08-1.52] and higher odds for intrahospital mortality (ICU vs. SU: OR, 2.11; 95% CI, 1.75-2.55; NW vs. SU: OR, 1.52; 95% CI, 1.23-1.89). A subgroup analysis of severely affected patients treated in dedicated NICUs (vs. SUs) showed that they had a lower risk of a poor outcome (OR, 0.45; 95% CI, 0.26-0.79). CONCLUSIONS: Treatment in SUs was associated with better functional outcome and reduced mortality compared with ICUs and NWs. Our findings support the current guideline recommendations to treat patients with intracerebral hemorrhage in SUs or NICUs and suggest that some patients may further benefit from NICU treatment.

Intravenous thrombolysis for acute ischaemic stroke in the elderly: data from the Baden-Wuerttemberg stroke registry.

BACKGROUND AND PURPOSE: In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed. METHODS: The data registry collected 101,349 patients with ischaemic stroke hospitalized from January 2008 to December 2012. Of these, 38,575 (38%) were aged 80 years and older and 10 286 (10.1%) underwent IVT. Favourable outcome at discharge was defined as modified Rankin Scale (mRS) ≤1 or not worse than prior to stroke. Multiple logistic regression models stratified by 10-year age groups were used to assess the relationship between IVT and mRS at discharge, adjusted for patient characteristics, admitting facility and length of hospital stay. RESULTS: The highest IVT rate was 15% in patients aged <50 years, with a continuous decline down to 8% in patients aged ≥90 years. Adjusted odds ratios and 95% confidence intervals for patients 80-89 years of age were 2.20 (1.95-2.47) (P < 0.0001) and 1.25 (0.88-1.78) (P = 0.21) for patients >90 years of age, compared to patients of the same age decade not treated with IVT. CONCLUSIONS: The evidence from routine hospital care in southwest Germany indicates that IVT is an effective treatment also for aged patients with ischaemic stroke in an age range between 80 and 89 years. Although no clear evidence for the effectiveness of IVT beyond 90 years was found, treatment should also be carefully considered in these patients. High age should not discourage from treatment.

Loss of estrogen-mediated immunoprotection underlies female gender bias in experimental Crohn's-like ileitis.

The incidence and severity of Crohn's disease (CD) are increased in female patients. Using SAMP1/YitFc (SAMP) mice, a spontaneous model of chronic intestinal inflammation that displays histologic and pathogenic similarities to human CD, we investigated the potential mechanism(s) contributing to sex differences observed in CD. Similar to gender differences observed in CD patients, SAMP female (SAMP-F) mice displayed an earlier onset and more severe ileitis compared with SAMP male (SAMP-M) mice. Furthermore, T-regulatory cells (Tregs) from gut-associated lymphoid tissue (GALT) of SAMP-F mice were reduced in frequency and impaired in their in vitro and in vivo suppressive functions compared with that of SAMP-M mice. Given the interaction between sex hormones and Treg function, we investigated the possible role of estrogen (E2) in SAMP ileitis. SAMP-M mice responded to exogenous E2 administration by expanding Treg frequency and reducing ileal inflammation, whereas SAMP-F mice were resistant. Conventional T cells and Tregs responded differentially to estrogen signaling, leading to distinct immunoprotective effects mediated by distinct estrogen receptor (ER) isoforms. These mechanisms were impaired in T cells from SAMP-F mice. Thus, hormone signaling influences the expansion and function of GALT Tregs in an ER-dependent manner and contributes to gender-based differences in experimental CD.

A consecutive and prospective stroke database covers the state of Baden-Wuerttemberg with 10.8 million inhabitants in Germany.

BACKGROUND: In 1998 Baden-Wuerttemberg (BW), a federal state in southwest Germany with 10.8 million inhabitants, implemented a structured medical concept for the treatment of acute stroke. METHODS: Since 2004 participation in the BW stroke database is mandatory for all hospitals in BW involved in acute stroke care. The stroke database includes all inpatients ≥18 years of age who have suffered an ischemic or hemorrhagic stroke within 7 days before hospitalization. This article presents methodological aspects and first results of the BW stroke database in the time period from 2007 to 2011. RESULTS: Annual inclusion numbers increased continuously (29,422 vs. 35,724, p < 0.001). Median age of stroke onset was stable over time. The proportion of stroke patients ≥80 years increased from 36.9 to 38.8% (p < 0.001). Rates of patients treated in neurology departments rose from 50.7 to 60.9% (p < 0.001) and numbers of patients treated in stroke units rose from 59.1 to 68.4% (p < 0.001). Admission via emergency medical systems increased from 42.8 to 49.7% (p < 0.001) and arrival within 3 h increased from 29.8 to 34.4% (p < 0.001). CONCLUSION: We present results from a large, prospective and consecutive stroke patient database. This first analysis demonstrates a continuous increase of absolute and relative numbers of stroke patients who arrive within 3 h after onset, are hospitalized in neurology departments and treated in stroke units, and are aged ≥80 years.

Treatment during primary HIV infection does not lower viral set point but improves CD4 lymphocytes in an observational cohort.

OBJECTIVE: To investigate if early treatment of primary HIV-1 infection (PHI) reduces viral set point and/or increases CD4 lymphocytes. METHODS: Analysis of two prospective multi-centre PHI cohorts. HIV-1 RNA and CD4 lymphocytes in patients with transient treatment were compared to those in untreated patients. Time to CD4 lymphocyte decrease below 350/ microl after treatment stop or seroconversion was calculated using Kaplan-Meier and Cox-PH-regression analyses. RESULTS: 156 cases of PHI were included, of which 100 had received transient HAART (median treatment time 9.5 months) and 56 remained untreated. Median viral load (563000 cop/ml vs 240000 cop/ml; p<0.001) and median CD4 lymphocyte (449/ microl vs. 613/ microl; p<0.01) differed significantly between treated and untreated patients. Median viral load was 38056 copies/ml in treated patients (12 months after treatment stop) and 52880 copies/ml in untreated patients (12 months after seroconversion; ns). Median CD4 lymphocyte change was +60/ microl vs. -86/ microl (p = 0.01). Median time until CD4 lymphocytes decreased to <350/ microl (including all patients with CD4 lymphocytes <500/ microl during seroconversion) was 20.7 months in treated patients after treatment stop and 8.3 months in untreated patents after seroconversion (p<0.01). Cox-PH analyses adjusting for baseline VL, CD4 lymphocytes, stage of early infection and symptoms confirmed these differences. CONCLUSIONS: Treatment during PHI did not lower viral set point. However, patients treated during seroconversion had an increase in CD4 lymphocytes, whereas untreated patients experienced a decrease in CD4 lymphocytes. Time until reaching CD4 lymphocytes <350/ microl was significantly shorter in untreated than in treated patients including patients with CD4 lymphocytes <500/ microl during seroconversion.

[Impairments of action control in the context of neuropsychological findings in schizophrenia]. / Störungen der Handlungskontrolle im Kontext neuropsychologischer Befunde bei Schizophrenie.

Based on a review of neurobiological and neuropsychological findings in schizophrenia, we illustrate how experimental neuropsychological research contributes to the understanding of schizophrenia. It is shown that cognitive performance deficits are a central feature of schizophrenia. They are closely connected with changes of brain physiology and appear to reflect disturbances of basic cognitive functions. It is difficult to identify these functions, because task performance usually taps various cognitive processes. However, isolation of functions is possible by experimental variation of tasks that require a small number of well defined processes. To illustrate this, we review several recent studies that experimentally analyzed deficits in the control of fast eye movements (saccades). In the antisaccade task schizophrenia patients show distinct, temporally stable and often replicated performance deficits. The reviewed studies suggest that these deficits predominantly reflect a weakness in the volitional initiation of action.

Epidemiological and clinical features of travel-associated cryptosporidiosis.

Data concerning the clinical and epidemiological features of travel-associated cryptosporidiosis are lacking. In order to investigate the impact of this disease on travellers' health, a retrospective study was conducted at the Institute of Tropical Medicine, Berlin. In total, 57 cryptosporidial infections were identified between 2000 and 2004, resulting in a prevalence of 2.9% in patients with travel-associated diarrhoea. Travel to south-central Asia, especially India, was associated with a higher prevalence of infection than was travel to other destinations. Clinically, the disease resembled giardiasis, but fever and arthralgias seemed to occur more frequently.

Mapping intramuscular tenderness variation in four major muscles of the beef round.

The objective of this study was to quantify intramuscular tenderness variation within four muscles from the beef round: biceps femoris (BF), semitendinosus (ST), semimembranosus (SM), and adductor (AD). At 48 h postmortem, the BF, ST, SM, and AD were dissected from either the left or right side of ten carcasses, vacuum packaged, and aged for an additional 8 d. Each muscle was then frozen and cut into 2.54-cm-thick steaks perpendicular to the long axis of the muscle. Steaks were broiled on electric broilers to an internal temperature of 71 degrees C. Location-specific cores were obtained from each cooked steak, and Warner-Bratzler shear force was evaluated. Definable intramuscular shear force variation (SD = 0.56 kg) was almost twice as large as between-animal shear force variation (SD = 0.29 kg) and 2.8 times as large as between-muscle variation (SD = 0.20 kg). The ranking of muscles from greatest to least definable intramuscular shear force variation was BF, SM, ST, and AD (SD = 1.09, 0.72, 0.29, and 0.15 kg, respectively). The BF had its lowest shear force values at the origin (sirloin end), intermediate shear force values at the insertion, and its highest shear force values in a middle region 7 to 10 cm posterior to the sirloin-round break point (P < 0.05). The BF had lower shear force values toward the ST side than toward the vastus lateralis side (P < 0.05). The ST had its lowest shear force values in a 10-cm region in the middle, and its highest shear force values toward each end (P < 0.05). The SM had its lowest shear force values in the first 10-cm from the ischial end (origin), and its highest shear force values in a 13-cm region at the insertion end (P < 0.05). Generally, shear force was lower toward the superficial (medial) side than toward the deep side of the SM (P < 0.05). There were no intramuscular differences in shear force values within the AD (P > 0.05). These data indicate that definable intramuscular tenderness variation is substantial and could be used to develop alternative fabrication and(or) merchandising methods for beef round muscles.

Evaluating the point of separation, during carcass fabrication, between the beef wholesale rib and the beef wholesale chuck.

This study determined whether there is a logical point of value change, related to either tenderness or consumer acceptance, at which to separate the beef carcass within the rib/chuck region. Rib/chuck rolls (RCR); (n = 30) consisting of the ribeye roll and chuck eye roll subprimals (2nd through 12th rib locations) were cut into 22 steaks each (two steaks per rib location), and Warner-Bratzler shear force and consumer purchase preference were evaluated for steaks at each rib location. Steaks from different locations of the RCR were composed of differing proportions of several muscles: longissimus muscle (LM), spinalis dorsi and multifidus dorsi (SM), and complexus (CO). The LM (4th to 12th rib) contained three tenderness regions: 7th through 12th rib, 5th and 6th ribs, and 4th rib regions (lowest, intermediate, and highest shear force values, respectively; P < 0.01). Shear force differed (P < 0.05) among rib locations for the SM (2nd to 9th rib), but no logical pattern was evident. The CO (2nd to 7th rib) was more tender toward the anterior end (P < 0.05). The region of the RCR represented by the 4th through 6th rib locations had steaks with higher weighted-average shear force (average shear force of each steak, weighted for surface area of each muscle) values than the remainder of the RCR (P < 0.05). Animal-to-animal variation in shear force was 36% greater than rib-to-rib variation in shear force; thus, statistically significant differences in tenderness among rib locations may be undetectable by consumers. Steaks (n = 330) were offered for sale at a retail supermarket and case time was monitored on each steak to determine consumer purchase preference. Steaks from the 2nd through 4th rib locations required more time to sell (P < 0.01) than steaks from the 5th through 12th rib locations. Two alternative locations for the rib/chuck separation point could be between the 6th and 7th ribs, yielding a ribeye subprimal useful in marketing a "premium quality" product, or between the 4th and 5th ribs, which would yield four more 2.5-cm ribeye steaks per carcass.

Increasing tenderness of beef round and sirloin muscles through prerigor skeletal separations.

Crossbred steers (n = 30) were used to explore and compare tenderness improvements in beef round and sirloin muscles resulting from various methods of prerigor skeletal separations. Animals were slaughtered according to industry procedures, and at 60 min postmortem one of six treatments was applied to each side: A) control, B) saw pelvis at the sirloin-round junction, C) separate the pelvic-femur joint, D) saw femur at mid-point, E) combination of B and C, and F) combination of B and D. After 48 h, the following muscles were excised from each side: semimembranosus, biceps femoris, semitendinosus, and adductor from the round; vastus lateralis and rectus femoris from the knuckle; and gluteus medius, biceps femoris and psoas major from the sirloin. Following a 10-d aging period, samples were removed from each muscle to determine the effect of treatment on sarcomere length and Warner-Bratzler shear force. Most skeletal separation treatments resulted in longer sarcomeres than controls for semimembranosus, adductor, semitendinosus, and gluteus medius muscles. All skeletal separation treatments yielded shorter sarcomeres for the psoas major as compared with controls. Warner-Bratzler shear force differed among treatments for rectus femoris, semitendinosus, and psoas major. For rectus femoris, treatments C, D, E, and F resulted in lower (P < 0.05) shear values than for controls. Treatments B, D, and F increased shear force of the semitendinosus relative to controls (P < 0.05) within muscle. Treatment F resulted in higher shear force values for the PM than controls (P < 0.05). Correlations between sarcomere length and shear force were found to be low and quite variable among muscles. In general, treatments increased sarcomere length of several muscles from the sirloin/round region, but had mixed effects on shear force values.

Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis.

BACKGROUND: The potential of ascorbic acid and two botanical decoctions, green tea and cat's claw, to limit cell death in response to oxidants were evaluated in vitro. METHODS: Cultured human gastric epithelial cells (AGS) or murine small intestinal epithelial cells (IEC-18) were exposed to oxidants - DPPH (3 microM), H2O2 (50 microM), peroxynitrite (300 microM) - followed by incubation for 24 hours, with antioxidants (10 microg/ml) administered as a 1 hour pretreatment. Cell number (MTT assay) and death via apoptosis or necrosis (ELISA, LDH release) was determined. The direct interactions between antioxidants and DPPH (100 microM) or H2O2 (50 microM) were evaluated by spectroscopy. RESULTS: The decoctions did not interact with H2O2, but quenched DPPH although less effectively than vitamin C. In contrast, vitamin C was significantly less effective in protecting human gastric epithelial cells (AGS) from apoptosis induced by DPPH, peroxynitrite and H2O2 (P < 0.001). Green tea and cat's claw were equally protective against peroxynitrite and H2O2, but green tea was more effective than cat's claw in reducing DPPH-induced apoptosis (P < 0.01). Necrotic cell death was marginally evident at these low concentrations of peroxynitrite and H2O2, and was attenuated both by cat's claw and green tea (P < 0.01). In IEC-18 cells, all antioxidants were equally effective as anti-apoptotic agents. CONCLUSIONS: These results indicate that dietary antioxidants can limit epithelial cell death in response to oxidant stress. In the case of green tea and cat's claw, the cytoprotective response exceed their inherent ability to interact with the injurious oxidant, suggestive of actions on intracellular pathways regulating cell death.

Male sex workers in three Australian cities: socio-demographic and sex work characteristics.

This article describes the socio-demographic and sex work characteristics of sex workers in Sydney, Melbourne, and Brisbane. A total of 185 male sex workers completed the questionnaire component of the study. The results of this study serve to debunk many of the myths surrounding the popular view of the male sex worker (MSW). The respondents in this study were on average 27 years old, and the majority had completed secondary education, with 30% having gained some form of tertiary qualification. Interestingly, those MSWs who had not completed secondary education were mostly street workers and were generally aged under 25 years. The majority of sex workers lived in rented accommodation, with only 6% reporting to be homeless. Half of all respondents identified as being "gay," 31% as "bisexual" and 5.5% as "straight." More than half of the respondents were in a permanent relationship. Only 7.3% of this group reported using heroin daily, although the majority consumed alcohol, tobacco, marijuana, and ecstasy. The majority of sex workers had been in the profession for less than six months, although some had been working in the industry for more than ten years. Most of the sex workers reported having taken an HIV test and a preference to offer safer sex. The article highlights ways in which the work context of MSW can be better understood and supported by education and public policy programs.

NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2.

BACKGROUND & AIMS: Selective cyclooxygenase (COX)-2 inhibitors produce less gastric damage than conventional nonsteroidal anti-inflammatory drugs (NSAIDs), suggesting that NSAIDs cause damage by inhibiting COX-1. We tested this hypothesis in rats by using a selective COX-1 inhibitor (SC-560). METHODS: The effects of SC-560, celecoxib (selective COX-2 inhibitor), or a combination of both inhibitors on gastric damage and prostaglandin synthesis were determined. Selectivity of the drugs for COX-1 vs. COX-2 was assessed in the carrageenan-airpouch model. A COX-1-preferential inhibitor, ketorolac, was also evaluated. The effects of these inhibitors on leukocyte adherence to vascular endothelium and on gastric blood flow were assessed. RESULTS: SC-560 markedly reduced gastric prostaglandin synthesis and platelet COX-1 activity, but spared COX-2 and did not cause gastric damage. Celecoxib did not affect gastric prostaglandin E(2) synthesis and did not cause gastric damage. However, the combination of SC-560 and celecoxib invariably caused hemorrhagic erosion formation, comparable to that seen with indomethacin. Ketorolac caused damage only at doses that inhibited both COX isoforms, or when given with a COX-2 inhibitor. Celecoxib, but not SC-560, significantly increased leukocyte adherence, whereas SC-560, but not celecoxib, reduced gastric blood flow. CONCLUSIONS: Inhibition of both COX-1 and COX-2 is required for NSAID-induced gastric injury in the rat.

A profile of the clients of male sex workers in three Australian cities.

OBJECTIVE: This paper describes the profile of clients as reported by 186 male sex workers in three Australian cities. METHOD: The data were collected using a diary which was completed after each commercial sexual encounter with a male client over a two-week period. The data reported in this study are based on reports from 2,088 sex encounters and a profile of 1,776 clients. RESULTS: The findings reveal, for example, that the most common source used for recruiting clients was advertisements, followed by escort agencies, although there were differences between the three cities; the majority of the clients were in their 40s but clients of street workers were younger; clients were most often classified as 'middle class', with differences by source of client recruitment; less than half the clients were identified as being gay and a significant number were identified as bisexual or straight; alcohol and drug use took place in a small percentage of the encounters; most workers had some information about their clients, such as occupation and home number; violence was infrequent; and unsafe sex was requested in a minority of the encounters. CONCLUSION: Overall, the results reveal that clients of male sex workers are a highly heterogeneous group. IMPLICATIONS: The paper highlights a number of issues which can further promote safety and public accountability in male sex work.

Phosphodiesterase inhibitors prevent NSAID enteropathy independently of effects on TNF-alpha release.

Although the ability of nonsteriodal anti-inflammatory drugs (NSAIDs) to injure the small intestine has been well established in humans and animals, the mechanism involved in this type of injury has yet to be elucidated. The cytokine tumor necrosis factor-alpha (TNF-alpha) has recently been demonstrated to play a critical role in the pathogenesis of NSAID-induced gastric damage. We therefore assessed the possibility that TNF-alpha is similarly involved in the pathogenesis of NSAID-induced small intestinal injury. Administration of multiple doses (n = 4) of diclofenac, but not a single dose, resulted in profound macroscopic damage in the intestine and significantly increased levels of TNF-alpha in intestinal tissue and bile. Pretreatment of rats with a phosphodiesterase inhibitor, pentoxifylline, theophylline, or rolipram, significantly attenuated the macroscopic intestinal ulceration produced by diclofenac administration. However, inhibition of TNF-alpha release with thalidomide or immunoneutralization with a polyclonal antibody directed against TNF-alpha failed to afford any protection. These results suggest that the cytokine TNF-alpha does not play a critical role in NSAID-induced small intestinal injury. Therefore, phosphodiesterase inhibitors mediate their protective effect through a mechanism independent of TNF-alpha synthesis inhibition.

Identification of bacterial isolates from biofilters as Paracoccus alkenifer sp. nov. and Paracoccus solventivorans with emended description of Paracoccus solventivorans.

Two groups of strains isolated from biofilters for the treatment of waste gases were assigned to the genus Paracoccus by phylogenetic and chemotaxonomic methods. All type strains of the genus Paracoccus were compared with these groups using 16S rDNA sequence analysis, fatty acid patterns and physiological reaction profiles. For both groups, the nearest related reference species was Paracoccus solventivorans based on 16S rDNA sequence similarity. However, whereas one group of isolates was identified as a member of this species by fatty acid analysis and DNA-DNA hybridization, the other group was proposed as a new species, Paracoccus alkenifer sp. nov. Fatty acid analysis showed the unusual fatty acid 20:1cis13 instead of 19:0 cyclo11-12 for P. alkenifer and P. solventivorans, and 14:1cis7 instead of 12:1cis5 for P. alkenifer and Paracoccus kocurii. By means of a GC-MS method, diaminopimelic acid was detected for P. solventivorans. Based on these results we propose an emended description for the species P. solventivorans.

[Computer-assisted neuropsychological training in neurological rehabilitation]. / Computerunterstütztes Hirnleistungstraining in der neurologischen Rehabilitation.

Using computer-assisted cognitive training to treat patients with cognitive disorders has proved a useful tool in neurological rehabilitation. This has been shown by positive experience in many rehabilitation clinics but also in numerous control studies investigating the efficiency of such training. Patients with attention deficits show the most pronounced improvements as the computer with its technical possibilities is an ideal training instrument because of stimulus representation and reaction time measures. In other areas, computer training has become an essential therapeutic means complementing other therapies. In a clinical environment it seems that computer training is essential because it enables attaining the necessary therapeutic density. However, training must be integrated and become part of a global therapeutic framework.

Selective inhibitors of cyclooxygenase-2: are they really effective, selective, and GI-safe?

Selective inhibitors of the "inducible" isoform of cyclooxygenase (COX-2) have been suggested to be effective analgesic and anti-inflammatory drugs while sparing the gastrointestinal (GI) tract of injury. There is some experimental and early clinical evidence to support this hypothesis. However, some important questions remain regarding the utility of selective COX-2 inhibitors. For example, estimates of the selectivity of COX-2 inhibitors based on in vitro studies are likely to be poor predictors of selectivity in vivo. Efficacy with selective blockade of COX-2 may be inferior to that achieved with combined inhibition of COX-1 and COX-2. Furthermore, in situations in which there is inflammation or ulceration in the GI tract, COX-2 produces prostaglandins that are essential for repair. In these circumstances, inhibition of COX-2 leads to delay of ulcer healing and exacerbation of inflammation. Some caution should therefore be exercised before the theory is fully accepted that selective COX-2 inhibitors are effective anti-inflammatory drugs that spare the GI tract of injury.

Biosynthesis of the labdane diterpene marrubiin in Marrubium vulgare via a non-mevalonate pathway.

The biosynthesis of the furanic labdane diterpene marrubiin has been studied in plantlets and shoot cultures of Marrubium vulgare (Lamiaceae). The use of [2-14C]acetate, [2-14C]pyruvate, [2-14C]mevalonic acid and [U-14C]glucose incorporation experiments showed that the labelling of sterols in etiolated shoot cultures of M. vulgare was in accordance with their biosynthesis via the acetate-mevalonate pathway. In contrast, the incorporation rates of these precursors into the diterpene marrubiin could not be explained by biosynthesis of this compound via the acetate-mevalonate pathway. Cultivation of etiolated shoot cultures of M. vulgare on medium containing [1-13C]glucose and subsequent 13C-NMR spectroscopy of marrubiin led to the conclusion that the biosynthesis of marrubiin follows a non-mevalonate pathway. All isoprenic units of 13C-labelled marrubiin were enriched in those carbons that correspond to positions 1 and 5 of a putative precursor isopentenyl diphosphate. This labelling pattern from [1-13C]glucose is consistent with an alternative pathway via trioses, which has already been shown to occur in Eubacteria and Gymnospermae. The labdane skeleton is a precursor of many other skeletal types of diterpenes. Therefore it becomes obvious that in connection with the few known examples of a non-mevalonate pathway to isoprenoids the formation of some isoprenoids in plants via a non-mevalonate pathway might be quite common.

Induction of cyclooxygenase 1 and 2 in the rat stomach during endotoxemia: role in resistance to damage.

BACKGROUND & AIMS: Prostaglandins and nitric oxide are key mediators of gastric mucosal defense. Endotoxemia alters gastric resistance to damage, but little is known of the effects of chronic endotoxemia on the expression of prostaglandin and nitric oxide synthases (NOSs). The effects of short- vs. long-term administration of endotoxin on gastric resistance to damage and on expression of NOS and prostaglandin synthesis were compared. METHODS: Rats were treated with short- or long-term bacterial endotoxin, after which susceptibility to ethanol-induced damage was assessed. The effects of various inhibitors of prostaglandin and NOS were examined. Expression of gastric NOS and cyclooxygenase (COX) messenger RNA (mRNA) were examined. RESULTS: Repeated administration of endotoxin increased gastric resistance to ethanol- but not indomethacin-induced injury. Indomethacin, but not a highly selective COX-2 inhibitor or an inducible NOS inhibitor, abolished long-term endotoxin-induced gastric resistance to injury. Expression of mRNA for both COX-1 and -2, but not for endothelial or inducible NOS, were significantly increased after long-term endotoxin administration. CONCLUSIONS: Repeated exposure to endotoxin resulted in increased resistance of the gastric mucosa to injury through a prostaglandin-dependent pathway. These prostaglandins were produced via COX-1, which like COX-2, is induced by endotoxin administration.