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During toilet training, constipation occurs before stool toileting refusal.

BACKGROUND: Previous studies demonstrated that constipation and painful defecation are associated with stool toileting refusal (STR), but whether they are the result of STR or occur before this behavior is not known. OBJECTIVE: To determine whether constipation and painful defecation occur as a result of STR or occur before STR. METHODS: Three hundred eighty children between 17 and 19 months of age participated in a prospective longitudinal study of toilet training. Children were monitored with telephone interviews every 2 to 3 months until the completion of daytime toilet training. Information obtained in follow-up interviews included parents' reports on the presence and frequency of hard bowel movements, painful defecation, and child toilet training behaviors. Children were defined as completing daytime toilet training when they were experiencing <4 urine accidents per week and < or =2 episodes of fecal soiling per month. Children were defined as having frequent hard bowel movements if the parents reported a hard bowel movement approximately once per week in > or =2 follow-up telephone interviews or more than once per week in 1 follow-up telephone interview. RESULTS: The mean age at the completion of daytime toilet training was 36.8 +/- 6.1 months (range: 22-54 months). Ninety-three children (24.4%) developed STR. Parents of children who developed STR, in comparison with the rest of the sample, were more likely to report that the child had experienced hard bowel movements (67.7% vs 50.9%), frequent hard bowel movements (29.0% vs 14.3%), and painful defecation (41.9% vs 27.9%). Of the children who experienced both STR and hard bowel movements, 93.4% demonstrated constipation before the onset of STR. In that group, parents reported hard bowel movements at almost one-half of all follow-up telephone interviews before the onset of STR. Of the children who experienced both STR and painful defecation, 74.4% experienced the first episode of painful defecation before the onset of STR. Children with frequent hard bowel movements demonstrated a longer duration of STR (9.0 +/- 6.5 vs 4.8 +/- 3.0 months). CONCLUSIONS: When hard bowel movements or painful defecation is associated with STR, the first episode of constipation usually occurs before the STR. The fact that hard bowel movements frequently occur before the onset of STR suggests that for many of these children constipation is a chronic problem that is not being treated effectively. Therefore, hard bowel movements and painful defecation are factors that potentially contribute to the STR and for the majority of children are not caused solely by the STR behavior. Additional studies are needed to determine whether earlier and more effective treatment of constipation could decrease the incidence of STR.

Child Behavior↗

Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training.

The present study investigated the influence of creatine and protein supplementation on satellite cell frequency and number of myonuclei in human skeletal muscle during 16 weeks of heavy-resistance training. In a double-blinded design 32 healthy, male subjects (19-26 years) were assigned to strength training (STR) while receiving a timed intake of creatine (STR-CRE) (n=9), protein (STR-PRO) (n=8) or placebo (STR-CON) (n=8), or serving as a non-training control group (CON) (n=7). Supplementation was given daily (STR-CRE: 6-24 g creatine monohydrate, STR-PRO: 20 g protein, STR-CON: placebo). Furthermore, timed protein/placebo intake were administered at all training sessions. Muscle biopsies were obtained at week 0, 4, 8 (week 8 not CON) and 16 of resistance training (3 days per week). Satellite cells were identified by immunohistochemistry. Muscle mean fibre (MFA) area was determined after histochemical analysis. All training regimes were found to increase the proportion of satellite cells, but significantly greater enhancements were observed with creatine supplementation at week 4 (compared to STR-CON) and at week 8 (compared to STR-PRO and STR-CON) (P<0.01-0.05). At week 16, satellite cell number was no longer elevated in STR-CRE, while it remained elevated in STR-PRO and STR-CON. Furthermore, creatine supplementation resulted in an increased number of myonuclei per fibre and increases of 14-17% in MFA at week 4, 8 and 16 (P<0.01). In contrast, STR-PRO showed increase in MFA only in the later (16 week, +8%) and STR-CON only in the early (week 4, +14%) phases of training, respectively (P<0.05). In STR-CRE a positive relationship was found between the percentage increases in MFA and myonuclei from baseline to week 16, respectively (r=0.67, P<0.05). No changes were observed in the control group (CON). In conclusion, the present study demonstrates for the first time that creatine supplementation in combination with strength training amplifies the training-induced increase in satellite cell number and myonuclei concentration in human skeletal muscle fibres, thereby allowing an enhanced muscle fibre growth in response to strength training.

Adult↗

[Analysis of serum antibodies to alpha-streptococci in patients with tonsil-related pustulosis palmaris et plantaris].

To determine the systemic immune response to alpha-streptococci (Str. sanguis, Str. salivarius and Str. mitis) and beta streptococcus (Str. pyogenes T12) in patients with tonsil related pustulosis palmaris et plantaris (PPP), we measured serum antibody levels to whole cell body antigens of Streptococcus (Str.) sanguis, Str. salivarius, Str. mitis or Str. pyogenes by enzyme-linked immunosorbent assay (ELISA). The serum IgG antibody levels to alpha-streptococci, Str. sanguis and Str. salivarius were significantly higher in patients with PPP (n = 44) than in patients with recurrent tonsillitis (RT: n = 25) and in healthy adults (n = 17). Serum antibody IgG level to Str. pyogenes was not different among the 3 groups. The IgA antibody levels against any Streptococcus strain were not different among the 3 groups. The IgM antibody levels to Str. pyogenes were significantly higher in patients with RT than in patients with PPP. In western blot analysis, the serum IgG antibodies against 25-27 kDa protein from whole cell body of Str. sanguis, Str. salivarius and Str. mitis were found more frequently in patients with PPP than in healthy adults. However, the western blot profile in Str. pyogenes was not different between PPP and healthy adults. No significant difference was seen in the western blot profile of IgM or IgM antibodies to any streptococcal whole cell bodies. These data suggest that systemic hyper immune response to alpha-streptococci may be present in patients with tonsil-related PPP and the 25-27 kDa protein of the organism may be the target for this immunologic abnormality.

Adult↗

Strychnine-induced potassium current in CA1 pyramidal neurones of the rat hippocampus.

1. Direct actions of strychnine (Str) and brucine (Bru) on the dissociated hippocampal CA1 neurones of the rat have been investigated with the whole-cell mode of the patch-clamp technique. 2. At a holding potential (VH) of -20 mV, both Str and Bru elicited outward current at concentrations over 10(-5) M. The reversal potential of Str-induced current (EStr) was -77.8 mV, which was close to the K+ equilibrium potential (EK = -80.3 mV). The change in EStr for a ten fold change in extracellular K+ concentration was 58 mV, indicating that the membrane behaves like a K+ electrode in the presence of Str. 3. The concentration-response curves for Str and Bru were bell-shaped, and nearly maximum response occurred at 10(-4) M for Str and 3 x 10(-4) M for Bru. The maximum current amplitude induced by Bru was about 80% of that induced by Str. A transient 'hump' current appeared immediately after the wash-out of external solutions containing Str and Bru at concentrations higher than 10(-4) and 3 x 10(-4) M, respectively. 4. The Str-induced current (IStr) was antagonized by K+ channel blockers such as Ba2+, tetraethylammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration-dependent manner. IStr was insensitive to glibenclamide, a blocker of ATP-sensitive K+ channels. 5. Internal perfusion with 10 mM BAPTA did not affect the Str-induced IK. Depletion of the intracellular Ca2+ store by caffeine had no effect, indicating that intracellular Ca2+ does not mediate the Str-induced activation of K+ conductance.6. Both guanosine-5'-0-3-thiotriphosphate (GTPyS) and guanosine-5'-O-thiodiphosphate (GDPPS) suppressed the Str-induced IK, the former action appearing more rapidly than the latter. The results suggest that the GTP binding proteins are involved in this Str response.7. When neurones were loaded with cholera toxin (CTX) or pertussis toxin (PTX) through a patch pipette, PTX suppressed the Str response whereas CTX did not, suggesting that G, and/or Go might be involved in the Str-induced IK.

Animals↗

[Prognostic significance of ST segment change in acute myocardial infarct].

The extent of ST segment elevation resolution (STR) 180 minutes after initiation of streptokinase treatment for acute myocardial infarction within 6 hours after onset of symptoms is an excellent early prognostic indicator that can be easily determined in all patients. This presentation is based on a meta-analysis from 3 thrombolysis studies including 3,912 patients. About 50% of patients had complete STR (> or = 70%). They had small enzymatic infarct sizes and well preserved left ventricular function associated with an excellent chance of survival. Patients with partial STR (< 70 to 30%) developed larger infarcts, but had still a relatively low mortality. To assess the optimal cut-off point that best predicts an increased mortality risk, the squared standardized log odds ratio statistics as a function of the hypothetical cut-off points in STR was used. A cut-off point around 30% STR was associated with an extraordinarily strong predictive power. The 35-day cardiac mortality with STR < 30% was 12.7% as compared to 2.1% for patients who had complete STR and 4.2% for those who had partial STR. Based on STR, age, medical history, and simple parameters at admission, a low risk population can be defined that includes about 50% of all patients aged < or = 70 years, and 20% of older patients. The 35-day and 1-year mortality rates for the group of younger patients was 1.4% and 2.7%, respectively, and for the older age group 5.0% and 7.9%. It appears highly unlikely that aggressive testing and interventions would have any measurable beneficial effect on such a good outcome. In thrombolytic therapy comparative trials STR may perform well as a surrogate endpoint, since it is more powerful than 90 minutes post-thrombolytic patency rates and early mortality, in a statistical sense. This is especially true for Phase-II dose-finding studies and the use as a surrogate or even primary endpoint in phase-III trials. In addition, STR may be very helpful for safety monitoring, interim analyses, and subgroup analyses in megatrials with the endpoint mortality. Use of STR can result in a substantial reduction in the required sample size. However, at least 1 pivotal mortality trial cannot be replaced by STR trials, since STR does not reflect the risk of intracranial hemorrhages and other bleeding complications.

Adult↗

Penicillin and netilmicin in treatment of experimental enterococcal endocarditis.

Successful therapy of enterococcal endocarditis requires the use of a combination of penicillin plus an aminoglycoside. The effectiveness of penicillin (Pen), streptomycin (Str), and netilmicin (Net), a new aminoglycoside, alone and in combination, were studied in vitro and in the treatment of left-sided enterococcal endocarditis in rabbits. In vitro Pen+Str or Net resulted in a more rapid and more complete bactericidal effect than Pen, Str, or Net alone against a Str-susceptible strain of enterococcus (strain 1). Against a highly Str-resistant strain (strain 2), Pen+Net showed an advantage over Pen, Str, or Net alone, or Pen+Str. Endocarditis was produced in rabbits with strain 1 or 2, and treatment was initiated 24 h later. Rabbits were treated for 48 h or 5 days with procaine Pen, Pen+Str, or Pen+Net. With strain 1, numbers of enterococci in the vegetations decreased more rapidly with Pen+Str or Pen+Net treatment than with Pen, Str, or Net alone. With strain 2, Pen+Net showed a clear advantage over Pen, Str, Net, or Pen+Str. Net in combination with Pen showed synergistic in vitro activity and was more effective than Pen alone in the treatment of enterococcal endocarditis in rabbits caused by both Str-susceptible and Str-resistant strains.

Animals↗

Spinal strychnine alters response properties of nociceptive-specific neurons in rat medial thalamus.

Experiments in both conscious and anesthetized animals indicate that intrathecal (i.t.) strychnine (STR; glycine receptor antagonist) produces acute, reversible allodynia, as evidenced by inappropriate behavioral and autonomic responses to cutaneous tactile stimuli. Although STR is known to produce disinhibition of afferent input to the spinal cord, changes in spinal reflexes cannot fully explain the complex behaviors observed following i.t. STR. Which supraspinal sites are involved in STR-dependent allodynia and how this abnormal somatosensory message is relayed to these sites remain to be determined. The medial thalamus contains many nociceptive-specific (NS) neurons and is believed to be involved in mediating the affective-motivational aspects of pain. It is thus important to determine whether spinally administered STR elicits changes in the responses of medial thalamic NS neurons. Extracellular single-unit recordings were conducted in urethan-anesthetized rats (290-490 g). A detailed characterization of 20 thalamic NS units (1 per rat; 2 in 1 case) was conducted before and immediately after i.t. STR (40 microg). Initially, all of the units in this study were classified as NS, because they were excited by noxious pinch but not by innocuous tactile stimuli. After i.t. STR, all (formerly NS) units exhibited significant responses to innocuous tactile stimuli (brush and/or air jet) applied to lumbar or sacral dermatomes. This effect of STR on thalamic NS neurons was acute and reversible. The majority of units (11 of 20) also exhibited an increase in spontaneous firing rate. Although the complete pinch receptive field (RF) could not be determined for all units, the available data indicate that the RFs for brush stimulation after i.t. STR were substantially different from the pre-STR pinch RFs for all but three units. The same i.t. STR injection that caused the observed changes in medial thalamus also produced allodynia, in the form of brush-evoked cardiovascular or motor responses, in 18 of the 19 rats. The ability of NS cells in medial thalamus to respond to tactile input after i.t. STR suggests that the STR lowers the threshold of nociceptive neurons that project directly and/or indirectly to medial thalamus. These observations suggest that ascending nociceptive pathways and medial thalamic structures contribute to the expression of STR-dependent allodynia.

Animals↗

Serotonin 2A and 2C receptor biosynthesis in the rodent striatum during postnatal development: mRNA expression and functional linkage to neuropeptide gene regulation.

The present study was designed to determine if there are region-specific differences in serotonin (5-HT) neurotransmission and 5-HT receptor expression that may limit the stimulatory effects of the 5-HT releaser p-chloroamphetamine (pCA) on striatal neuropeptide gene expression to the posterior striatum (P-STR) during postnatal maturation. Sprague-Dawley rat brains from postnatal days (PND) 1-35 were processed for 5-HT(2A) and 5-HT(2C) receptor mRNA expression by in situ hybridization and monoamine analysis by HPLC. Within the P-STR, 5-HT(2A) receptor mRNA expression reached young adult (PND 35) levels by PND 3, while levels in the A-STR were significantly less (range: 1.43 +/- 0.219-6. 36 +/- 0.478) than P-STR (5.36 +/- 0.854-12.11 +/- 1.08) at each respective age throughout the time course. 5-HT(2C) receptor mRNA expression reached young adult levels at PND 7 in the A-STR and by PND 3 in the P-STR. At each PND age 5-HT(2C) receptor mRNA levels within the P-STR were significantly less (6.23 +/- 1.02-12.32 +/- 0.427) than the A-STR (7.31 +/- 1.65-26.84 +/- 2.24). 5-HT content increased across the developmental time course within the P-STR (5.01 +/- 0.327-15.7 +/- 1.03 ng/mg protein) and A-STR (2.97 +/- 0. 223-11.2 +/- 0.701 ng/mg protein). Four hours following injection (i. p.) of pCA (10 mg/kg), preprotachykinin (PPT) mRNA levels increased 89% in the P-STR but not the anterior (A-STR) striatum of the 3-week-old rat, which were prevented by preinjection (30 min, i.p.) of the 5-HT(2) receptor antagonist ritanserin (1 mg/kg). Together, these data suggest that faster maturity of 5-HT(2A) receptor expression in the P-STR may be sufficient to convey the region-specific acute stimulatory effects of pCA on PPT mRNA transcription in the developing rodent striatum. These results provide further evidence that the influence of 5-HT on neuropeptide gene expression is far stronger in caudal vs. rostral striatal regions during postnatal development.

Animals↗

Strychnine-sensitive modulation is selective for non-noxious somatosensory input in the spinal cord of the rat.

Touch-evoked allodynia, an important symptom of clinical neural injury pain, can be modelled acutely and reversibly in the urethane-anesthetized rat using intrathecal (i.t.) strychnine (STR). Allodynia, after i.t. STR (40 micrograms), is manifest as a significant enhancement of cardiovascular and motor responses evoked by normally innocuous brushing of the hair (hair deflection), as compared to responses evoked by either hair deflection after i.t. saline (SAL), or to i.t. STR (40 micrograms) with no tactile stimulus. The present study investigated: (1) the pharmacology of afferent neural inputs involved in STR-dependent allodynia using neonatal capsaicin and the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX); and (2) the effect of i.t. STR on responses evoked by peripheral noxious stimulation. Neonatal capsaicin (25 mg/kg, s.c., post-natal day (PND) 1, and 50 mg/kg, s.c., PND 2, 3, 4, 11, 25, 55 and 85) significantly attenuated the responses evoked by noxious mechanical, thermal or chemical stimuli, but had no effect on STR-dependent allodynia. All hair deflection-evoked, STR-dependent responses were dose-dependently inhibited by i.t. NBQX. The ED50 values and 95% confidence intervals were 10.4 micrograms (5.5-19.6) for the motor withdrawal response, 14.4 micrograms (8.6-24.0) for changes in MAP and 12.2 micrograms (6.8-21.8) for changes in HR. Cortical EEG synchrony was unchanged by i.t. NBQX confirming its spinal locus of action. Intrathecal STR neither reduced nor enhanced the responses elicited by noxious stimuli in capsaicin- or vehicle-pretreated rats. These results indicate that STR-dependent allodynia is initiated by primary afferents not normally involved in nociception (possibly A beta-fibers), and that STR-sensitive modulation in the spinal cord is selective for non-noxious sensory input. The sensitivity of STR-dependent allodynia to non-NMDA receptor antagonists, and the failure of i.t. STR to produce hyperalgesia to mechanical, thermal or chemical noxious stimuli, confirm the independence of nociceptive pathways and STR-sensitive afferent inputs in this model.

Anesthesia, General↗

Stimulated serotonin release from hyperinnervated terminals subsequent to neonatal dopamine depletion regulates striatal tachykinin, but not enkephalin gene expression.

Dopamine (DA) depletion in neonatal rodents results in depressed tachykinin and elevated enkephalin gene expression in the adult striatum (STR). Concurrently, serotonin (5-HT) fibers sprout to hyperinnervate the DA-depleted anterior striatum (A-STR). The present study was designed to determine if increased 5-HT release from sprouted terminals influences dysregulated preprotachykinin (PPT) and preproenkephalin (PPE) mRNA expression in the DA-depleted STR. Three-day-old Sprague-Dawley rat pups received bilateral intracerebroventricular injections of vehicle or the DA neurotoxin 6-hydroxydopamine (6-OHDA, 100 microg). Two months later, rats received a single intraperitoneal injection of vehicle or the acute 5-HT releasing agent p-chloroamphetamine (PCA; 10 mg/kg). Rats were killed 4 h later and striata processed for monoamine content by HPLC-ED and mRNA expression by in situ hybridization within specific subregions of the A-STR and posterior striatum (P-STR). 6-OHDA treatment severely (>98%) reduced striatal DA levels, while 5-HT content in the A-STR was significantly elevated (doubled), indicative of 5-HT hyperinnervation. Following 6-OHDA, PPT mRNA levels were depressed 60-66% across three subregions of the A-STR and 52-59% across two subregions of the P-STR, while PPE mRNA expression was elevated in both the A-STR (50-62%) and P-STR (55-82%). PCA normalized PPT mRNA levels in all regions of the DA-depleted A-STR and P-STR, yet did not alter PPE levels in either dorsal central or medial regions from 6-OHDA alone, but reduced PPE to control levels in the dorsal lateral A-STR. These data indicate that increased 5-HT neurotransmission, following neonatal 6-OHDA treatment, primarily influences PPT-containing neurons of the direct striatal output pathway.

3,4-Dihydroxyphenylacetic Acid↗

beta-Casein mRNA sequesters a single-stranded nucleic acid-binding protein which negatively regulates the beta-casein gene promoter.

beta-Casein gene expression in mammary epithelial cells is under the control of the lactogenic hormones, glucocorticoids, insulin, and prolactin. The hormonal control affects gene transcription, and several regulatory elements in the beta-casein gene promoter between positions -80 and -221 have previously been identified. A region located in the promoter between positions -170 and -221 contains overlapping sequences for negative and positive regulatory elements. A sequence-specific single-stranded DNA-binding factor (STR), composed of two proteins with molecular masses of 35 and 54 kDa, recognizes the upper strand of this region and has a repressing role in transcription. High-level STR binding activity was observed in nuclear extracts from mammary glands of pregnant and postlactating mice and from noninduced HC11 mammary epithelial cells, cells with a low level of transcriptional activity of the beta-casein gene. STR activity is downregulated in mammary epithelial cells during lactation of the animals and after lactogenic hormone induction of HC11 cells in culture. These cells strongly transcribe the beta-casein gene. We investigated the mechanism of downregulation and found that a lactogenic-hormone-induced molecule (I-STR) inhibits STR from binding to its DNA target. I-STR is composed of RNA. STR is sequestered into the cytoplasm by I-STR after lactogenic hormone induction of mammary epithelial cells and remains present in an RNA-bound form. A high-affinity STR binding site was found in the 5' untranslated region of beta-casein mRNA. We propose that beta-casein mRNA can function as I-STR. beta-Casein mRNA may positively regulate its own transcription by translocating STR from the nucleus to the cytoplasm. The beta-casein STR binding sequence increases expression of a transfected beta-galactosidase gene when it is placed into the 5' untranslated region sequence of the mRNA. STR may have a positive role in posttranscriptional regulation.

Animals↗

Production of exopolysaccharides by submerged culture of an enthomopathogenic fungus, Paecilomyces tenuipes C240 in stirred-tank and airlift reactors.

The objective of this study was to investigate the effect of shearing effect on the production of exopolysaccharides (EPS) from an enthomopathogenic fungus, Paecilomyces tenuipes C240 in a stirred-tank reactor (STR) and in an airlift reactor (AR). The optimal agitation rate for the production of EPS in the STR was 150 rpm with the mycelial morphology of hairy pellets, where the final concentration and the specific production rate of EPS were 2.33 g l(-1) and 0.312 gg(-1) h(-1), respectively. However, the maximum concentration of biomass (21.06 g l(-1)) in the STR was obtained at a high agitation speed of 300 rpm. The specific production rate of EPS (0.456 gg(-1) h(-1)) in the AR was significantly higher than that achieved in the STR, in which the typical morphological form of mycelium was a loose clump. The three EPS groups in the STR (designated as STR-I, -II, and -III) and two groups of EPS in the AR (designated as AR-I and -II) were obtained from the culture filtrates by a gel filtration chromatography on Sepharose CL-6B. The molecular weights of STR-I, STR-II, STR-III, AR-I, and AR-II were determined to be 1,820, 25, 1.8, 1,160, and 6.7 kDa, respectively. An agitation rate of 150 rpm in the STR was selected as the optimal culture condition for maximum EPS production (2.33 g l(-1)), which was similar to the level achieved in the AR (2.30 g l(-1)). The carbohydrate composition in each EPS was quite different from each other: the major component was glucose (in STR-I, -III, and AR-I), mannose (in STR-II), and arabinose (in AR-II). In contrast, no significant difference in amino acid composition was observed.

Ascomycota↗

[ST-segment resolution as a simple tool for the assessment of successful primary coronary intervention at a microvascular level].

BACKGROUND: The primary success of the coronary artery reperfusion by primary coronary intervention (PCI) is almost angiographically assessed by TIMI flow score. The perfusion at a microvascular level can be inadequate despite the restoring of normal flow in the epicardial coronary artery. One of the options of successful reperfusion at a microvascular level is the measurement of ST-segment resolution (STR) after primary PCI. AIM: The assessment of ST-segment resolution in patients indicated for primary PCI and the comparison with clinical data. METHODS: The authors studied 149 patients (68.5 % men) with ST elevation acute myocardial infarction treated by primary PCI. The ECG was taken at the time of arriving patient at coronary unit and compared with ECG early after primary PCI. Patients were divided into 3 groups according to the grade of STR: with complete (> or = 70%), partial (30-69%) and none (< 30%) STR. The lead with maximal changes (STEmax) and sum of ST elevation (STEsum) were assessed. RESULTS: 42 (28.2 %) patients had complete STR, 55 (36.9%) partial STR and 52 (34.9%) patients didn't achieve STR. STR was connected with better left ventricular ejection fraction, which was in group with complete STR 50% compared with 39.4% in group without STR (p < 0.0001). Patients with symptoms of heart failure on admission (Killip II-IV) had complete STR only in 4 cases (10%) compared with patients without heart failure (Killip I), where was complete STR in 38 (34.8%), (p = 0.003). There wasn't noted significant difference in STR at dependence on glycoprotein IIb/IIIa inhibitors administration. A normal or mildly slower coronary flow (TIMI 2, 3) was achieved in 146 patients (98%), 3 patients (2%) had inadequate coronary flow after primary PCI (TIMI 0, 1). CONCLUSIONS: The evaluation of early ECG changes is simple method for the assessment of primary PCI success at the microvascular level. Our outcomes confirm a differences in achievement of optimal epicardial coronary flow and a perfusion at microvascular level.

Angioplasty, Balloon, Coronary↗

Stromelysin-3 is overexpressed by stromal elements in primary non-small cell lung cancers and regulated by retinoic acid in pulmonary fibroblasts.

Stromelysin-3 (STR-3) is a recently characterized matrix metalloproteinase (MMP) that was cloned on the basis of differential expression in benign and malignant breast tumors. This MMP has a unique processing mechanism and substrate specificity. Unlike previously characterized MMPs that are secreted as inactive zymogens, STR-3 is processed within the constitutive secretory pathway and secreted as an active enzyme. Although STR-3 has a characteristic MMP structure, the enzyme does not hydrolyze many of the extracellular matrix components that are substrates for other MMPs. However, STR-3 cleaves certain serine protease inhibitors (serpins), including the alpha 1 proteinase inhibitor (alpha 1 anti-trypsin). Because alpha 1 proteinase inhibitor deficiency has a known pathogenetic role in pulmonary disease, the role of STR-3 in non-small cell lung carcinomas (NSCLC) is of great interest. STR-3 transcripts and protein were significantly more abundant in primary NSCLC than in adjacent normal lung specimens in an extensive panel of stage I-III squamous cell and adenocarcinomas. The major form of STR-3 detectable in the primary NSCLC was the mature fully processed active enzyme. STR-3 transcripts and protein were primarily localized to NSCLC stromal elements, prompting analysis of STR-3 induction in normal pulmonary fibroblasts. Although STR-3 could be induced in normal pulmonary fibroblasts with growth factors (basic fibroblast growth factor and platelet-derived growth factor) and/or 12-O-tetradecanoylphorbol-13-acetate, STR-3 induction was inhibited by all-trans retinoic acid, a commonly used chemopreventive agent for aerodigestive tract malignancies. Taken together, these data suggest that STR-3 may be a novel marker and potential therapeutic target in NSCLC.

Base Sequence↗

Effect of clopidogrel plus aspirin on ST segments in patients with ST-elevation acute myocardial infarction.

Spontaneous ST-segment resolution (STR) after acute ST-elevation myocardial infarction is associated with favorable outcomes. Effect on STR of newer, more powerful antiplatelet and antithrombotic agents is unclear. The aim of this study was to identify independent clinical and angiographic predictors of STR in patients with ST-elevation acute myocardial infarction before percutaneous coronary intervention. We studied 206 patients admitted with ST-elevation acute myocardial infarction, of whom 37 (18%) had STR. There were 12 deaths (5.8%) that occurred in the group without spontaneous STR. Patients with spontaneous STR were younger (55 vs 61 years old, p = 0.02), had shorter duration of symptoms (117 vs 212 minutes, p <0.0001), had preserved ejection fraction (55% vs 40%, p <0.0001), had shorter hospital stays, and had lower in-hospital arrhythmias or death. Independent predictors of STR, identified by stepwise logistic regression analysis, were early clopidogrel administration (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.00 to 4.40, p = 0.045), single-vessel disease (OR 2.85, 95% CI 1.22 to 6.70, p = 0.02), chest pain duration (OR 0.98, 95% CI 0.98 to 0.99, p <0.0001), collaterals (OR 4.3, 95% CI 1.7 to 10.8, p = 0.002), circumflex as a culprit vessel (OR 4.74, 95% CI 1.5 to 14.95, p = 0.008), and coronary thrombus noted on angiography (OR 5.76, 95% CI 1.63 to 20.4, p = 0.006). In conclusion, early clopidogrel administration is associated with, and likely causal for, STR. Patients with thrombus, collateral flow, and circumflex culprit vessel are more likely to have STR. In addition, our study confirms previous findings that patients with STR have preserved left ventricular function and better hospital outcomes compared with those without STR.

Aspirin↗

Stromelysin-3 is induced in tumor/stroma cocultures and inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism.

Stromelysin-3 (STR-3) is a recently characterized matrix metalloproteinase (MMP) with a unique pattern of expression and substrate specificity. Unlike other MMPs, STR-3 is consistently and dramatically overexpressed by multiple epithelial malignancies, including carcinomas of the breast, lung, colon, head and neck, and skin. Recent studies suggest that STR-3 promotes the local establishment of epithelial malignancies, contributing to tumor cell survival and implantation in host tissues; however, STR-3's mechanism of action remains undefined. STR-3 is a stromal cell product, prompting speculation that infiltrating stromal cells secrete STR-3 in response to tumor-derived factors. To explore this possibility, we developed a tumor/"stroma" coculture assay in which non-small cell lung cancer (NSCLC) cell lines were grown on confluent monolayers of normal pulmonary fibroblasts. In these tumor/stroma cocultures, NSCLCs stimulate normal pulmonary fibroblasts to secrete STR-3 and release extracellular basic fibroblast growth factor. Thereafter, STR-3 is processed at a unique internal sequence via a basic fibroblast growth factor- and MMP-dependent mechanism to a previously unidentified 35-kDa protein that lacks enzymatic activity. 35-kDa STR-3 is the most abundant STR-3 protein in tumor/stroma cocultures and is only detected when normal pulmonary fibroblasts are cultured with malignant bronchial epithelial cells. Therefore, the tumor-specific processing of STR-3 to the 35-kDa protein is likely to be an important regulatory mechanism.

Amino Acid Sequence↗

Molecular genetics of resistance to macrolides, lincosamides and streptogramin B (MLS) in streptococci.

Resistance to macrolides-lincosamides-streptogramin B (MLS phenotype) appears in almost all streptococcal species isolated from man. Genes coding for MLS resistance are located on plasmids and one MLS resistance transposon has been described. MLS resistance genes have also been found in a large number of plasmid-free strains. Plasmids of 17 to 20 megadaltons (Mdal) that code either for MLS or for both MLS and chloramphenicol resistance are found in streptococci of groups A, B, C, D (Streptococcus faecalis) and G. These plasmids have broad host ranges (conjugative intraspecies, interspecies and intergeneric transfer), display similar restriction enzyme patterns and share a considerable degree of homology (78 to 95%). One smaller non-conjugative MLS resistance plasmid has been isolated from Str. sanguis (4.5 Mdal). In group D (Str. faecalis, Str. faecium) streptococci, MLS resistance genes are also found on plasmids that carry other antibiotic resistance (tetracycline, chloramphenicol, high-levels of streptomycin and kanamycin). These multi-resistance plasmids are either conjugative or non-conjugative and are of various sizes and molecular species and those that have been tested have narrow host-ranges. The MLS resistance genes of one multi-resistant plasmid, isolated from a strain of Str. faecalis, are located on a transposon of 3.3 Mdal, Tn917. Hybridization studies, with MLS determinants as probes, reveal homologies among various plasmid-borne MLS resistance sequences. Elements that are thought to be chromosome-borne mediate multiple antibiotic resistance (including MLS) in streptococci of groups A, B, C, D (Str. bovis), F, G, Str. pneumoniae, Str. mitis, Str. sanguis and Str. milleri. Strains harbouring such elements contain no detectable plasmid DNA. In some of the strains these elements are conjugative; their resistance markers transfer en bloc at low frequency and display narrow host ranges. Such elements, from Str. pyogenes and Str. agalactiae, were found to translocate onto various streptococcal haemolysin-bacteriocin plasmids.

Anti-Bacterial Agents↗

Strychnine-induced potassium current in isolated dorsal root ganglion cells of the rat.

1. Effects of strychnine (Str) on the dissociated dorsal root ganglion (DRG) cells of the rat have been investigated in whole-cells configuration by a conventional patch-clamp technique. 2. gamma-Aminobutyric acid (GABA)-induced Cl- current (ICl) increased sigmoidally with increasing concentration. The half-maximal response (Ka) was 3 x 10(-5) M and the Hill coefficient was 1.5. Both Str and bicuculline inhibited the GABA-induced ICl in a concentration-dependent manner. 3. Str itself could elicit the current at concentrations over 10(-5) M, at which concentrations the GABA response was completely suppressed. The concentration-response curve for the Str-induced current was bell-shaped, and a nearly maximum response occurred at 3 x 10(-4) M. A transient 'hump' current appeared immediately after the wash-out of external solution containing high concentrations of Str over 3 x 10(-4) M. 4. The Str-induced outward current and a transient 'hump' current were augmented by the removal of extracellular K+ and were suppressed by the substitution of intracellular K+ for Cs+. But the current was not sensitive to extracellular Na+, Ca2+ and Cl-. 5. The reversal potential of Str-induced current (EStr) was -75 mV, which was close to the K+ equilibrium potential (EK = -76.3 mV). The change of EStr for a ten fold change in extracellular K+ concentration was 58 mV, indicating that the membrane behaves like a K+ electrode in the presence of Str. The reversal potential of the 'hump' current was also close to EK. 6. The Str-induced outward current was antagonized by K+ channel blockers such as Ba2+, tetraethylammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration-dependent manner. 7. The Str-induced K+ current was not affected by internal perfusion of bis(gamma-aminophenoxy)ethane-N, N,N',N-tetraacetic acid (BAPTA), indicating that the Str response does not result in the activation of K+ conductance by the intracellular Ca2+.

Animals↗