The effect of adrenergic agonists on the systemic response to hemorrhage

An in vivo antitumor screening of extracts of Gomphrena martiana indicated positive activity in the petroleum ether extract, and its further bioactivity-directed fractionation resulted in a lipophilic flavonoid fraction. Upon inoculation of various doses of 5,6,7-trisubstituted flavones on two murine tumor lines, Sarcoma 180 and Ehrlich's carcinoma, a decrease of tumor growth was observed. An in vitro KB cultured cell screen indicated cytotoxicity.     

T-lymphocytes from AIDS patients are unable to synthesize ribonucleotides de novo in response to mitogenic stimulation. Impaired pyrimidine responses are already evident at early stages of HIV-1 infection

Proliferative defects have been reported at the level of DNA synthesis, even in T-lymphocytes from asymptomatic human immunodeficiency virus type-1+ (HIV-1+) patients. Since purine and pyrimidine ribonucleotide availability is crucial for proliferation, we compared the ability of HIV-1- and HIV-1+ T-lymphocytes (> 95% CD4+ and CD8+) to activate de novo biosynthetic and salvage pathways following phytohemagglutinin stimulation using 14C-labeled precursors. The striking abnormality already detectable in asymptomatic patients' cells was the impaired ability of CTP, UDP-Glc, and UTP pools to expand over 72 h (44-70% of control), although ATP and GTP pools and responses were normal. In symptomatic patients, resting T-cells showed markedly reduced pyrimidine pools (53-74% of control) with no change following activation. Relatively normal ATP, GTP, and NAD pools masked the same impaired response of de novo synthesis to activation, with ATP and GTP being reduced by 50% at 48 h. Purine salvage was more active than the control in unstimulated HIV-1+ cells. This impaired de novo synthesis in HIV-1+ T-lymphocytes severely restricts the availability of ribonucleotides for vital growth-related activities such as membrane expansion and strand break repair as well as DNA and RNA synthesis. The data indicate that resting T-lymphocytes from symptomatic patients survive through enhanced salvage, but the stimulation induces metabolic cell death, and provide an explanation for the activation-associated lymphocyte death seen in HIV-1+ T-lymphocytes.     

Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography

An isocratic high-performance liquid chromatographic method with ultraviolet detection was utilized for the investigation of the pharmacokinetics of naringenin and its glucuronide conjugate in rat plasma and brain tissue. Plasma and brain tissue were deproteinized by acetonitrile, then centrifuged for sample clean-up. The drugs were separated by a reversed-phase C18 column with a mobile phase consisting of acetonitrile-orthophosphoric acid solution (pH 2.5-2.8) (36:64, v/v). The detection limits of naringenin in rat plasma and brain tissue were 50 ng/ml and 0.4 microg/g, respectively. The glucuronide conjugate of naringenin was evaluated by the deconjugated enzyme beta-glucuronidase. The naringenin conjugation ratios in rat plasma and brain tissue were 0.86 and 0.22, respectively, 10 min after naringenin (20 mg/kg, i.v.) administration. The mean naringenin conjugation ratio in plasma was approximately four fold that in brain tissue.     

Lumbar spine magnetic resonance imaging: comparison between fast spin echo proton density and spin echo T1 axial scans

Spin echo (SE) T1 axial scans are routinely obtained in magnetic resonance imaging of the lumbar spine in many centres. This study directly compared matched SE T1 and fast SE (FSE) proton density (PD) axial scans. Both SE T1 and FSE PD axial scans of the lumbar spine were obtained in 116 consecutive patients. The imaging parameters (field-of-view, slice thickness, interslice gap, number of excitations and matrix size) and scan levels were identical for each pair of sequences. At two selected levels, L4/5 and L5/S1, various structures were independently graded by two observers. In 232 lumbar levels analysed, the bone marrow, epidural fat, disc, extradural nerve root and facet joint were equally well seen on both sequences by both observers (combined mean grades of 2.93-2.99). The thecal sac was marginally better depicted on FSE PD than on SE T1 images, with mean grades of 2.96 and 2.88, respectively. The psoas muscle was adequately visualized for diagnostic purposes on both sequences (mean grades of 2.30-2.32). The cauda equina were better seen on FSE PD (mean grade 1.92) than on SE T1 (mean grade 1.00) images. In conclusion, FSE PD scans are comparable to and may potentially replace SE T1 axial MR scans of the lumbar spine.     

Expandable metal stents for the treatment of colonic obstruction: techniques and outcomes

Modulation of CD8(+) T-cell responses specific for an exogenous antigen by epitope variants would be advantageous to develop a novel means of antigen-specific immune regulation. We have analyzed CD8(+) T-cell responses to single amino acid-substituted variants of a peptide corresponding to residues 142-149 (p142-149; LAYFYPEL) of alphas1-casein, a major milk allergen, which is a dominant determinant restricted by H-2Kb. An analog peptide L142I with a substitution of Ile for Leu at the nonanchor N-terminal residue induced more IFN-gamma secretion than p142-149 from specific CD8(+) T cells. Furthermore, L142I could prime CD8(+) T cells more efficiently in vivo, and these L142I-primed cells secreted more IFN-gamma than p142-149-primed CD8(+) T cells upon stimulation with p142-149 in vitro. These findings are mainly explained by the greater ability of L142I to form stable Kb-peptide complexes. These findings indicate that appropriate analog peptides may be useful as efficient inducers of CD8(+) T cells which recognize the parent peptide and secrete IFN-gamma, a potent inhibitor of Th2-dependent events, including IgE production.     

Effect of alcohol consumption on adult and aged bone: composition, morphology, and hormone levels of a rat animal model

To determine the effect of life-long alcohol consumption on the adult and aged rat model, 4-week-old, female Sprague-Dawley rats were divided into three diet groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin substituted calories supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Proximal tibiae (primarily cancellous bone) and femora (primarily cortical bone) were removed for analysis after 3, 6, 9, 12, or 18 months on the diets. Serum was collected for analysis of calcium levels, the calcium regulating hormones; parathyroid hormone, 25-hydroxyvitamin D, calcitonin, corticosterone, estradiol, testosterone, and IGF-1. Creatinine, SGOT/AST, and SGPT/ALT levels were measured to determine kidney and liver integrity. Previous studies, with young animals, showed that chronic alcohol consumption during the age of bone development reduced bone density and bone mass in both cortical and cancellous bone. The present study demonstrates that these reductions last throughout life, whereas morphological values, such as length and diameter, attain control levels. Calcium regulating hormones and sex hormones are essentially normal and do not appear to be the primary causative agent for adult alcohol-induced osteopenia, but it appears to be due to a more direct effect of alcohol on bone cells.     

Intraventricular chemotherapy in neonatal meningitis

All of 16 infants with neonatal meningitis treated during a 30-month period were found to have accompanying ventriculitis at the time of the initial ventricular puncture. Fifteen of these infants were caused by gramm-negative organisms. All infants received antibiotics systemically and intraventricularly via an implanted ventriculostomy reservoir or by direct ventricular injection. Antibiotic concentrations within the ventricular fluid were monitored during chemotherapy; the complications encountered during treatment are discussed. Fifteen infants survived the infection; of these, seven infants were normal at follow-up examinations. In our experience intraventricular chemotherapy as an adjunct to systemic administration of antibiotics has greatly reduced the mortality rate in neonatal meningitis.     

The cardiovascular effects of diazepam and of diazepam and pancuronium during fentanyl and oxygen anaesthesia

A study of the physiological behaviour of the synthetic compound Orthonil (alpha-chloro-beta-(3-chloro-o-tolyl)-propionitrile revealed a strong auxin activity in higher plants. Otherwise, Orthonil appeared not to be a herbicide-auxin. It is metabolized intensively in plant tissues. Among the identified metabolites, two compounds were detected which also exert a high auxin activity. It is concluded that at least a part of the apparent auxin activity of Orthonil may be due to alpha-(3-chloro-o-tolyl) acetic acid, one metabolite of Orthonil. Although Orthonil strongly stimulates elongation growth, this growth is not accompanied by a stimulated ethylene evolution as is the case with other auxins. A possible metabolic pathway of Orthonil is discussed.     

Probability of malignant degeneration of ovarian tumors. Clinical study on the probability of malignant degeneration

More than 600 cases of ovarian tumors were analyzed for histological type, age of patient, bilateral occurrence, mobility and malignant degeneration in restant ovaries. Tumors of germinal epithelial origin show the highest incidence (24%) of malignant degeneration, tumors of germ cells the lowest (3,5%). Incidence of malignant degeneration increases in relation to the age of the patient from 2% (and under 30 years) to 36,5% (60-70 years). Each form of tumor has its typical age peak, which is about 20 years higher for carcinomas than for their benign counterpart. Bilateral ovarian tumors are malignant in 29%, one-sided only in 13%. Among freely movable ovarian tumors, only 6% enclose a malignant tumor, among adhaerent ones 34%. The examination of the prognosis of granulosacell-tumors, dysgerminomas and teratoblastomas is based on a larger material.     

Renal transport of urate during diuretic-induced hypouricemia

The effect of two weeks administration of a uricosuric diuretic (SKF-62698) on renal urate handling has been examined in 11 normal men. Plasma urate concentrations had declined by more than 60 per cent after two weeks. Urate excretion per unit of glomerular filtration rate and urate clearance (Curate) per unit of glomerular filtration rate were increased after the administration of SKF-62698. The importance of intact tubular secretion of urate in producing these changes was assessed by administering pyrazinamide, an agent that curtails urate secretion, to each participant. The decrements in urate excretion and clearance produced by pyrazinamide both increased significantly, whereas the residual urate excretion rates and clearances not suppressible by pyrazinamide were only minimally altered by SKF-62698 treatment. These results suggest that the excretion of secreted urate was enhanced by prolonged administration of SKF-62698, probably secondary to the inhibition of postsecretory urate reabsorption. In addition, because the nonsuppressible urate excretion did not decline despite a 63 per cent reduction in the plasma urate, it is likely that the reabsorption of filtered urate also was impaired by SKF-62698.