Iron chelation effects on lipid peroxidation, inflammation and ventricular performance in a rat model of isoproterenol induced acute myocardial stress.

Acute cardiac pathologies represent one of the leading causes of death, while iron metabolism is recognized to be implicated in reactive oxygen species production, lipid peroxidation, and inflammation. The aim of the present study was to assess iron chelation effects in isoproterenol (ISO) induced acute cardiac stress. We divided male Wistar rats into preventive and secondary treatment groups, with the active arm consisting in deferiprone (DFP), a lipid permeable chelator. Mortality of ISO was 10-18.18% in both preventive and secondary groups. We analyzed serum and myocardial tissue parameters of inflammation, iron dynamics, and lipid peroxidation, accompanied by ultramicroscopy, histological, and ultrasound-derived parameters of left ventricular function. Results reveal that ISO-mediated lipid peroxidation and inflammation are alleviated by administration of DFP, with negligible effect on systemic ferroregulation dynamics and global ventricular function (as assessed by ultrasound). DFP administration after cardiovascular stress is associated with a decrease in lipid peroxidation and inflammation, without an improvement in gross left ventricular parameters.

Chronic oral trimethylamine-N-oxide administration induces experimental incipient atherosclerosis in non-genetically modified mice.

Atherosclerosis is a chronic inflammatory disease of the arterial wall involving inflammation, redox imbalance, and impaired cholesterol transport. A high level of trimethylamine-N-oxide (TMAO) produced by meat and fat metabolism are involved in atherosclerosis development, but the exact relationship with inflammation is not completely clear. The study aimed to identify a possible association between TMAO; atherosclerotic changes in the aortic root; oxidative stress; and inflammation quantified by highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), and interleukin-1beta (IL-1ß) levels. TMAO dihydrate was administered via gastric gavage to 20 male Wistar rats for 90 days; one separate group received vehicle. The TMAO-treated animals were divided into two groups: one group received a low dose of TMAO (20 mg/day) and the other group received a high dose of TMAO (40 mg/day). Malondialdehyde (MDA), proinflammatory markers - IL-1ß, TNF-α, and hsCRP, total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, and glucose were assessed 30 and 90 days after TMAO administration. Additionally, conventional histopathology and immunohistochemistry for collagen I distribution were performed. MDA, hsCRP, TNF-α, and IL-1ß levels increased after 90 days of TMAO administration in conjunction with significant changes suggestive of incipient atherosclerosis and inflammation of the aortic root. The increase was higher in the group treated with 40 mg/day TMAO compared with the group treated with 20 mg/day TMAO. Additionally, blood levels of TMAO were significantly correlated with hsCRP, TNF-α, IL-1ß levels, but also with MDA, low HDL-cholesterol levels, and high triglyceride levels. The increase in MDA and inflammatory cytokines and modification of lipid metabolism markers may explain the pro-atherogenic effect of TMAO.

Characterization and biological effects of Hypericum extracts on experimentally-induced - anxiety, oxidative stress and inflammation in rats.

Anxiety disorders can associate with oxidative stress and immune system alterations. Our study aimed to chemically analyze Hypericum maculatum (HM) and Hypericum perforatum (HP) dry extracts and to evaluate their effects along with quercetin (Q), on brain oxidative stress biomarkers: malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD), inflammatory cytokines: interleukin-1α, (IL-1α), IL-1ß, regulated on activation normal T cell expressed and secreted (RANTES), interferon (IFN), monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein (MIP) and serum corticosterone levels. Nuclear transcription factor κB (NFκB) signaling pathway in the hippocampus and frontal lobe in rats with N-methyl-9H-pyrido[5,4-b]indole-3-carboxamide (FG-7142) experimental-induced anxiety were also investigated. The chemical analyses of total hypericins were performed by spectrophotometric analysis and hypericin, hyperforin and polyphenols derivatives were quantified by chromatographic methods. The animals were divided in 6 groups: carboxymethylcellulose 2% (CMC); CMC + FG; alprazolam (APZ) + FG; Q + FG; HM + FG; HP + FG. APZ (0.08 mg/kg b.w.), Q (30 mg/kg b.w.), HM and HP (350 mg/kg b.w.) were orally administered for 21 days. FG (7.5 mg/kg b.w.) was intraperitoneally (i.p.) injected in a single dose. Q and hypericum extracts (HpE) exerted anti-inflammatory (decreased IL-1α, IL-1ß, MCP1, IFN and MIP mainly in hippocampus) and antioxidant effects (decreased MDA levels, increased CAT and SOD activity), enhanced NFκB and pNFκB expressions in the brain and reduced serum corticosterone levels. Our findings suggest that HpE may improve anxiety-like behavior, offer brain protection by modulation of oxidative stress and inflammation, and can contribute to overall biological activity of natural compounds-rich diet.

Ultrasound assessment of transversus abdominis muscle contraction ratio during abdominal hollowing: a useful tool to distinguish between patients with chronic low back pain and healthy controls?

Spine stabilisation exercises, in which patients are taught to preferentially activate the transversus abdominus (TrA) during "abdominal hollowing" (AH), are a popular treatment for chronic low back pain (cLBP). The present study investigated whether performance during AH differed between cLBP patients and controls to an extent that would render it useful diagnostic tool. 50 patients with cLBP (46.3 ± 12.5 years) and 50 healthy controls (43.6 ± 12.7 years) participated in this case-control study. They performed AH in hook-lying. Using M-mode ultrasound, thicknesses of TrA, and obliquus internus and externus were determined at rest and during 5 s AH (5 measures each body side). The TrA contraction-ratio (TrA-CR) (TrA contracted/rest) and the ability to sustain the contraction [standard deviation (SD) of TrA thickness during the stable phase of the hold] were investigated. There were no significant group differences for the absolute muscle thicknesses at rest or during AH, or for the SD of TrA thickness. There was a small but significant difference between the groups for TrA-CR: cLBP 1.35 ± 0.14, controls 1.44 ± 0.24 (p < 0.05). However, Receiver Operator Characteristics (ROC) analysis revealed a poor and non-significant ability of TrA-CR to discriminate between cLBP patients and controls on an individual basis (ROC area under the curve, 0.60 [95% CI 0.495; 0.695], p = 0.08). In the patient group, TrA-CR showed a low but significant correlation with Roland Morris score (Spearman Rho = 0.328; p = 0.02). In conclusion, the difference in group mean values for TrA-CR was small and of uncertain clinical relevance. Moreover, TrA-CR showed a poor ability to discriminate between control and cLBP subjects on an individual basis. We conclude that the TrA-CR during abdominal hollowing does not distinguish well between patients with chronic low back pain and healthy controls.

Multidisciplinary treatment for chronic pain: a systematic review of interventions and outcomes.

OBJECTIVES: To provide an overview of the effectiveness of multidisciplinary treatments of chronic pain and investigate about their differential effects on outcome in various pain conditions and of different multidisciplinary treatments, settings or durations. METHODS: In this article, the authors performed a systematic review of all currently available randomized controlled trials (RCTs) fulfilling the inclusion criteria, by using a recently developed rating system aimed to assess the strength of evidence with regard to the methodological quality of the trials. RESULTS: Compared with other non-disciplinary treatments, moderate evidence of higher effectiveness for multidisciplinary interventions was shown. In contrast to no treatment or standard medical treatment, strong evidence was detected in favour of multidisciplinary treatments. The evidence that comprehensive inpatient programmes were more beneficial that outpatient programmes was moderate. Fibromyalgia and chronic back pain patients tended to profit more substantially than patients with diverse origins or chronic pain diagnoses. No evidence was found that treatment variables, such as duration or programme components, were influential for the success of the intervention. CONCLUSION: A standard of multidisciplinary programmes should be internationally established to guarantee generally good outcomes in the treatment of chronic pain. Our results highlight the lack of quality of design, execution or reporting of many of the RCTs included in this article. Future studies should more specifically focus on differential effects of treatment components and patient variables, allowing the identification of subgroups, which most probably would profit from multidisciplinary pain programmes.

Abdominal muscle size and symmetry at rest and during abdominal hollowing exercises in healthy control subjects.

The symmetry of, and physical characteristics influencing, the thickness of the lateral abdominal muscles at rest and during abdominal exercises were examined in 57 healthy subjects (20 men, 37 women; aged 22-62 years). M-mode ultrasound images were recorded from the abdominal muscles at rest and during abdominal hollowing exercises in hook-lying. The fascial lines bordering the transvs. abdominis, obliquus internus and obliquus externus were digitized and the absolute thickness, relative thickness (% of total lateral thickness) and contraction ratio (thickness during hollowing/thickness at rest), as well as the asymmetry (difference between sides expressed as a percent of the smallest value for the two sides) for each of these parameters were determined for each muscle. Both at rest and during hollowing, obliquus internus was the thickest and transvs. abdominis the thinnest muscle. There were no significant differences between left and right sides for group mean thicknesses of any muscle; however, individual asymmetries were evident, with mean values for the different muscles ranging from 11% to 26%; asymmetry was much less for the contraction ratios (mean % side differences, 5-14% depending on muscle). Body mass was the most significant positive predictor of absolute muscle thickness, for all muscles at rest and during hollowing, accounting for 30-44% variance. Body mass index explained 20-30% variance in transvs. abdominis contraction ratio (negative relationship). The influence of these confounders must be considered in comparative studies of healthy controls and back pain patients, unless groups are very carefully matched. Asymmetries observed in patients should be interpreted with caution, as they are also common in healthy subjects.

Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) in the cochlea: evidence for specific transcript expression of PAC1-R splice variants in rat microdissected cochlear subfractions.

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from the hypothalamus, named for its high potency in stimulating adenylyl cyclase in pituitary cells. PACAP acts through the specific receptor PAC1-R to modulate the action of neurotransmitters, and additionally, to regulate cell viability via autocrine/intracrine mechanisms. Evidence has now been obtained that PACAP and multiple splice variants of PAC1-R are expressed in the rat cochlea. mRNA for PACAP precursor protein is found by reverse transcription-polymerase chain reaction (RT-PCR) in microdissected cochlear lateral wall, organ of Corti, and spiral ganglion subfractions. A specific pattern of expression of mRNA for PAC1-R splice variants, which mediate the response to PACAP, has been revealed by RT-PCR and cloning for the cochlear subfractions. Transcript for the short form of PAC1-R is found in all three subfractions. Four additional splice variants -- hop1, hop2, hip, and a novel hop1 splice variant -- are expressed in the lateral wall. For the amino terminus splice region of PAC1-R, a new splice variant has been detected in the organ of Corti, representing a deletion of the first 7 of 21 amino acids detected in the PAC1-R very-short sequence. Overall, from message determinations in cochlear subfractions, there are five PAC1-R splice variants in the lateral wall, two in the organ of Corti and one in the spiral ganglion, indicating multiple possible responses to PACAP and/or mechanisms to modulate the response to PACAP in the cochlea. The variety of PAC1-R splice variants expressed may reflect the diversity in cell function between subfractions that is modulated by PACAP. The neuropeptide and its specific receptor have been immunolocalized in the lateral wall, the source of the largest number of cochlear PAC1-R splice variants. The receptor was targeted by primary antibodies which would elicit immunoreactivity for all splice variants of PAC1-R detected with RT-PCR, and evidence has been obtained with Western blot analysis suggesting that PAC1-R is glycosylated in vivo. Within the lateral wall, PACAP and PAC1-R were immunolocalized primarily to the stria vascularis, with immunoreactivity for both neuropeptide and receptor increasing from the basal to apical cochlear turns. Within the stria, PACAP immunoreactivity was localized to the basolateral extensions of marginal cells, while PAC1-R was clearly associated with tight junctions between the marginal cells close to the endolymphatic compartment. In addition, evidence was obtained that PAC1-R was associated with endothelial cells of the capillaries in the stria vascularis. The large number of splice variants expressed, coupled to the specificity in linkage between PAC1-R splice variants and G-protein-coupled second messenger pathways, could provide a mechanism to closely modulate tight junction integrity in the stria vascularis, impacting the endolymphatic potential.

[Detection of Treponema pallidum DNA and RNA in clinical material from patients with syphilis at different stages]. / Vyiavlenie DNK i PNK Treponema pallidum v klinicheskom materiale u patsientov s razlichnymi stadiiami sifilisa.

The results of the development and approval of methods for the detection of T. pallidum DNA and 16S rRNA in clinical material (blood plasma, serous exudates) are presented. T. pallidum DNA was detected with the use of primers to the gene coding protein with a moleculat weight of 47 kD and T. pallidum RNA, with the primers to gene 16S rRNA. The isolation, reverse transcription and amplification of DNA and RNA was carried out in the presence of inner DNA and RNA control respectively. The analytical sensitivity of the developed method was 400 DNA copies per ml. The characteristics of analytical and diagnostic specificity were 100%. The specimens of blood plasma, taken from 292 patients with syphilis at different stages before specific antibacterial therapy, were tested by the PCR. The detection rate of T. pallidum DNA and RNA in blood plasma was, respectively, 91% and 100% in primary seropositive syphilis, 68% and 79% in secondary early syphilis, 19% and 26% in latent unverified syphilis. In secondary relapsing syphilis T. pallidum DNA and RNA were detected in 92% and in latent early syphilis, in 14% of patients. T. pallidum nucleic acids were detected in 1 patient at the seronegative period of primary syphilis. No positive result was obtained in the PCR analysis in any of the patients with diagnosed seroresistance, latent late syphilis and tertiary syphilis. In the study of material taken from chancres of 11 syphilis patients the data obtained by dark-field microscopy and the PCR analysis completely coincided.

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder.

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Application of a lectin from the mushroom Polysporus squamosus for the histochemical detection of the NeuAcalpha2,6Galbeta1,4Glc/GlcNAc sequence of N-linked oligosaccharides: a comparison with the Sambucus nigra lectin.

The lectin from the mushroom Polysporus squamosus (PSL) has an extended carbohydrate combining site, which exhibits a high specificity and affinity toward the NeuAc5alpha2,6Galbeta1,4Glc/GlcNAc trisaccharide sequence of asparagine-linked oligosaccharides. Therefore, PSL should be a superior reagent to the lectin from Sambucus nigra (SNA), which does not discriminate between alpha2,6-linked NeuAc5 present either in asparagine- or serine/threonine-linked oligosaccharides. We have prepared a digoxigenin-conjugated PSL and applied it for histochemistry and blotting. We observed a more restricted staining pattern by PSL as compared to SNA in paraffin sections from different rat organs. Pretreatment of sections with N-glycanase F abolished PSL staining indicating that it interacts only with asparagine-linked oligosaccharides. Furthermore, PSL staining was neuraminidase sensitive. In contrast, SNA staining was only partially sensitive to N-glycanase F pretreatment demonstrating that it was in part due to alpha2,6-linked NeuAc5 present in serine/threonine-linked oligosaccharides. The most striking observation in this regard was that PSL, in contrast to SNA, did not stain the mucus of sheep submandibular gland, which is extremely rich in serine/threonine-linked Neu5Acalpha2,6N-acetylgalactosamine. Furthermore, in some tissues neuraminidase pretreatment resulted in increased intensity of SNA staining probably due to binding to exposed terminal N-acetylgalactosamine residues. Collectively, these results indicate that PSL is a useful tool for the histochemical detection of alpha2,6-linked NeuAc5 in asparagine-linked oligosaccharides.

Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group.

BACKGROUND: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania. METHODS: Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. RESULTS: Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively). CONCLUSION: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.

Nonunion of the mandible: an analysis of contributing factors.

PURPOSE: The aim of this study was to review our experience of nonunion of mandible fractures and to compare this information with the past and present literature. The analysis also evaluated risk factors and those conditions that lead to nonunion so that the complication may be better managed and possible avoided. PATIENTS AND METHODS: A retrospective review of mandible fractures in a major medical center was carried out on patients treated from 1994 through 1998. The nonunion cases were evaluated for factors such as age, sex, race, cause of fracture, location of fracture, delay until the patient obtained treatment, teeth in the fracture line, use of antibiotics, multiplicity of fractures, degree of fragmentation, medical problems, and drug and alcohol abuse. The adequacy of reduction and appropriateness of the fixation techniques were evaluated by analysis of the postoperative imaging studies. Postoperative occlusion and patient compliance were also included in the evaluation. RESULTS: Of the 906 patients with 1,432 mandible fractures, there were 25 nonunion complications, for an incidence of 2.8%. Most patients with nonunion were men who had received the fracture as a result of an altercation. The nonunion was frequently noted in the body, and was almost twice as common (39% vs 17.6%) in patients with multiple fractures than in a randomly selected group who did not have the complication. Delayed treatment was noted in 8 of the patients, and teeth were present in the fracture line in another 8. Alcohol and drug abuse were prevalent, and 1 of 5 of the patients removed their fixation devices. Eight patients were believed to be stabilized inadequately, and 1 patient also had a poor reduction. Osteomyelitis was a common complication. CONCLUSIONS: The incidence of nonunion appears to be unchanged over time regardless of the varied and presumably advanced methods of fixation and reduction. Multiple fractures were a contributory factor, and the body of the mandible appeared to be a common site. Many patients had osteomyelitis associated with the nonunion. Inadequate stabilization or reduction were important causes. Other suspected contributory factors included failure to provide antibiotics, delay in treatment, teeth in the fracture line, alcohol and drug abuse, inexperience of the surgeon, and lack of patient compliance.

Thomsen-Friedenreich glycotope is expressed in developing and normal kidney but not in renal neoplasms.

The Thomsen-Friedenreich glycotope (TF) is considered a general carcinoma autoantigen and is therefore of importance in cancer diagnosis and immunotherapy. We report the distribution of the TF glycotope in developing and adult human kidney and renal neoplasms. A monoclonal antibody and the lectin amaranthin were used to study the TF and its sialylated, masked form by immunohistochemistry and immunoblotting. In developing kidney, the TF was restricted to the loop of Henle, distal tubules, and peripheral collecting ducts, whereas its sialylated form was detectable in all epithelial differentiations derived from the 2 embryonic anlagen, the metanephrogenic blastema being unreactive. This pattern was essentially preserved in adult kidney, with TF labeling beginning in the thick ascending limb and extending into the collecting ducts of outer medulla. The sialylated TF glycotope was additionally observed in ascending thin limbs. The TF was exclusively expressed in the luminal cell surface and hence was inaccessible to immune reactions. Analysis of a spectrum of renal neoplasms failed to detect the TF, with the exception of occasional staining of tubules in nephroblastoma. Moreover, the sialylated TF was only detectable in oncocytoma, chromophobe renal cell carcinoma, cystic nephroma, nephroblastoma, and nephroblastomatosis complex and occasionally in type 1 papillary renal cell carcinoma. Thus, the TF and its sialylated form are expressed in normal developing and adult kidney. However, the TF does not seem to represent a tumor-associated glycotope in human kidney, nor does it appear to be of value in diagnosis and immunotherapy of renal neoplasms.

Focal loss of CD44 variant protein expression is related to recurrence in superficial bladder carcinoma.

The majority of papillary transitional cell carcinomas of the bladder are localized tumors at initial diagnosis; identification of those developing recurrence and an aggressive behavior is important. CD44 variant proteins have been implicated in tumor progression and metastasis, and a correlation with adverse prognosis has been demonstrated in a variety of human tumors. Here, the usefulness of conventional CD44 protein immunohistochemistry as a prognostic parameter for recurrence of superficial transitional cell carcinomas was assessed in paraffin sections of 241 tumors with long-term follow-up. A highly significant association was found between focal loss of CD44v3 and -v6 immunostaining and short recurrence-free interval in noninvasive (pTa) transitional cell carcinomas (P = 0.005), but not in minimally invasive (pT1) carcinomas (P = 0.78). Our results indicate the value of conventional CD44 immunohistochemistry as an additional tool for identifying patients at high risk for recurrence of pTa transitional cell carcinomas. They also point to biological differences between noninvasive and minimally invasive transitional cell carcinomas of the bladder.

Specialized expression of simple O-glycans along the rat kidney nephron.

Glycosyltransferases can exhibit tissue-specific expression. By histochemistry glycosyltransferases and their products can be localized to specific cell types in organs of complex cellular composition. We have applied the lectin Amaranthin, having a nominal specificity for Galbeta1,3GalNAcR and Neu5Ac2,3Galbeta1, 3GalNAcalpha-R, and a monoclonal antibody raised against Galbeta1, 3GalNAcalphaR to examine the distribution of these simple O-glycans in adult rat kidney. The monoclonal antibody stained ascending thin limbs of Henle, distal convoluted tubules, and collecting ducts of cortex and outer medulla. Remarkably, the ascending thick limb of Henle, located between ascending thin limb and distal convoluted tubules, was unreactive. However, Amaranthin staining was detectable in ascending thick limbs of Henle, in addition to the structures positive with the monoclonal antibody. In kidney extracts, two bands of approximately 160 kDa and >210 kDa were reactive with both Amaranthin and the monoclonal antibody. One band at approximately 200 kDa, and a smear at approximately 100 kDa, were reactive only with Amaranthin. Our data show that in rat kidney simple O-linked glycans are expressed in a highly specialized manner along the renal tubule and can be detected only on a few glycoproteins. This may reflect a cell-type-specific expression of the corresponding glycosyltransferases.

Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group.

OBJECTIVE: The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania. METHOD: The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score. RESULTS: The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group. CONCLUSIONS: The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.

Differentiation-related expression of the Thomsen-Friedenreich glycotope in developing human lung and in lung carcinoma: lack of association with malignancy.

BACKGROUND: It has been proposed that the Thomsen-Friedenreich glycotope represents a general carcinoma-associated antigen and a candidate for the development of a tumor vaccine. However, the expression of the unmasked and masked (sialylated) forms in lung carcinomas, as well as in developing and adult human lung, has not been documented sufficiently. METHODS: Sections from 82 lung carcinomas, including squamous cell carcinomas, adenocarcinomas, and large cell and small cell carcinomas, as well as sections of developing and adult human lung were studied using the lectin amaranthin and a monoclonal antibody. RESULTS: All lung carcinomas but one bronchiolo-alveolar carcinoma were unreactive for the Thomsen-Friedenreich glycotope, whereas its sialylated form was detectable in well-differentiated squamous cell carcinomas and adenocarcinomas, including bronchiolo-alveolar carcinomas. Both unmasked and masked Thomsen-Friedenreich glycotopes were undetectable in large cell and small cell lung carcinomas. In all developmental stages of lung, the Thomsen-Friedenreich glycotope was expressed only in epithelia of the most peripheral parts of the bronchial tree, whereas its sialylated form was expressed in epithelia of all parts of the bronchial tree. In adult lung, the Thomsen-Friedenreich glycotope was expressed in pneumocytes, whereas its sialylated form was expressed ubiquitously in all epithelia. CONCLUSIONS: The Thomsen-Friedenreich glycotope in human lung represents a differentiation antigen, rather than a carcinoma-associated antigen. The sialylated form is expressed constitutively in both developing and adult lung and well-differentiated lung carcinomas. Thus, the Thomsen-Friedenreich glycotope is of limited value in the diagnosis of lung carcinoma, and there is no rationale for a Thomsen-Friedenreich glycotope-based immunotherapy for patients with this disease.

Postcolumn radionuclide detection of low-energy beta emitters in capillary electrophoresis.

A postcolumn radionuclide detection system for capillary electrophoresis (CE) is described. Eluant from an electrophoresis capillary is directed onto a peptide binding membrane that has been previously coated with a solid scintillator. The membrane is moved in a preselected pattern relative to the fixed capillary outlet during electrophoresis. Light emission from scintillation is imaged onto a charge-coupled device (CCD) using a series of 35-mm camera lenses. Detection of two low-energy beta- emitters (35S and 3H) not previously reported for capillary electrophoresis is demonstrated. The separation efficiencies are similar to those obtained with on-line UV detection. The response for 35S-labeled methionine is linear (r2 = 0.996) from 66 amol to 11 fmol. Detection limits are 88 zmol (0.03 Bq) for 32P-labeled analytes, 17 amol (0.94 Bq) for 35S-labeled analytes, and 8 fmol (8.5 Bq) for 3H-labeled analytes.

Heart metabolic modifications induced by nifedipine treatment in normo- and hypertensive Wistar rats.

Male Wistar rats weighing 150 +/- 10 g at the beginning of the experiment were used. The animals were divided in to four groups: control group (C); Hypertensive group (H) (Hypertension induced by subcutaneously injecting desoxycorticosterone acetate: 14 mg/kg b. w./day and intragastric tubage administration of 30% sodium chloride: 3 g NaCl/kg b. w./day for 4 weeks); normotensive group receiving Nifedipine (N) (0.5 mg/Kg b. w./day); hypertensive group receiving Nifedipine (HN) (hypertension was induced as in group H and Nifedipine dose was as in group N). We observed that hypertensive status as well as Nifedipine treatment caused an increase of preference of rat heart muscle to utilize its glycogen as carbohydrate energy source instead of added glucose to incubation medium.