Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.     

Early treatment decisions with interferon-alfa therapy in early chronic-phase chronic myelogenous leukemia

PURPOSE: To determine, in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) on interferon alfa (IFNalpha), whether combining pretreatment characteristics and early response profiles would distinguish patients with differential benefits that would allow better decisions on subsequent therapy. PATIENTS AND METHODS: A total of 274 patients treated from 1982 through 1990 with IFNalpha regimens were analyzed. A second group of 137 patients treated with IFNalpha and low-dose cytarabine (ara-C) between 1990 and 1994 was later used to confirm the guidelines derived from the original study group analysis. Patients' pretreatment factors and response to IFNalpha therapy at 3, 6, and 12 months were analyzed in relation to subsequent achievement of major cytogenetic response. After univariate analysis of prognostic factors, a multivariate analysis selected, at 6 months, independent pretreatment factors that added to the response status in predicting subsequent outcome. The results were then applied at the 3- and 12-month periods and confirmed in the subsequent population. RESULTS: Response to IFNalpha therapy at 3, 6, and 12 months was a significant predictor of later major cytogenetic response. The presence of splenomegaly > or = 5 cm below the costal margin (BCM) or thrombocytosis > or = 700 x 10(9)/L pretreatment added significant independent prediction to response. At 6 months, patients with a partial hematologic response (PHR) or resistant disease had a less than 10% chance of achieving a later major cytogenetic response, as were those in complete hematologic response (CHR) and who had pretreatment splenomegaly and thrombocytosis. Applying the model at 3 months showed that only patients with < or = PHR and pretreatment splenomegaly or thrombocytosis at 3 months had such a low major cytogenetic response rate. Finally, at 12 months, patients with CHR still had a 15% to 25% chance of having a major cytogenetic response later if they did not have pretreatment splenomegaly and thrombocytosis. CONCLUSION: This analysis allows better selection of patients with Ph-positive CML on IFNalpha therapy for continuation of IFNalpha versus changing therapy early in the course of CML. For treatment programs that choose to change patients to other investigational therapies (eg, intensive chemotherapy and/or autologous stem-cell transplantation [SCT]), baseline outcome expectations are provided for patients continued on IFNalpha therapy, against which the results of new approaches can be compared.     

Ubiquitin and apoptosis in the corpus luteum of the marmoset monkey (Callithrix jacchus)

The thiazolidinedione analogue troglitazone is an antidiabetic agent that improves insulin resistance in rodents and humans. Although coronary artery disease is common in patients with the insulin resistance syndrome, the effects of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We therefore examined the effects of troglitazone on cell growth and glucose uptake in human aortic SMC. Mitogen-activated protein (MAP) kinase activity and glucose transporter (Glut) 1 mRNA levels were also studied. In the absence of troglitazone, insulin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC and troglitazone suppressed the increase of DNA synthesis in a dose-dependent manner. This growth suppression was accompanied by inhibition of MAP kinase activity. On the other hand, troglitazone significantly increased Glut 1 mRNA and enhanced glucose uptake in SMC. These results suggest that troglitazone affects the insulin signaling pathways in SMC and suppresses growth while promoting glucose uptake. Our findings support the application of troglitazone as an inhibitor of SMC proliferation in patients with insulin resistance.     

Growth, morphology and chemosensitivity studies on postconfluent cells cultured in 'V'-bottomed microtiter plates

This study assessed the growth pattern, cellular organisation and chemosensitivity of established human tumour cell lines growing as postconfluent cultures in 'V'-bottomed, 96-well microtiter plates. Cross-sections of the colon (HT29, SW620, SW1116), ovarian (A2780) and head and neck (UM-SCC-22B) carcinoma microcultures allowed in situ evaluation of the cellular organisation in the wells. After 5 days of growth, every cell line had reached confluence, but each of them displayed a specific pattern of cell stacking which ranged from two to ten layers. Postconfluent HT29 cells displayed morphologic features suggestive of some degree of enterocytic differentiation. Growth and cytotoxicity could be studied reliably and reproducibly in this system with the sulforhodamine B protein assay. Against HT29 postconfluent cultures, the EC50's (drug concentrations producing absorbance readings 50% lower than those of non-treated wells) of 5-fluorouracil and of the ether lipid, hexadecylphosphocholine, were 1 mM and 50 microM respectively. The possibility to perform chemosensitivity tests using semiautomated microtiter plate technology supports further evaluation of this system as an alternative antitumour drug testing model.     

Clinical presentation of herpes zoster in a Singapore hospital

The purpose of the study was to give a histological picture of the different skin regions of the mammary gland in mares. Special emphasis on the dark coating in the sulcus intermammarius was given. As a result, the dark pigmented udder skin can be subdivided into the skin of the Corpus mammae, the sulcus intermammarius and the teat skin. In the sulcus intermammarius the whole epidermis was considerably thicker than usual, especially the stratum corneum (up to 70 layers of cornified layers) and the stratum spinosum. In general, the squamous keratinocytes were unusually large. The histological preparations of the coating revealed a stratum corneum instead of a supposed secretion of the sebaceous glands. The dermal papillae ended immediately below the stratum corneum.     

Projection status of calbindin- and parvalbumin-immunoreactive neurons in the superficial layers of the rat's superior colliculus

Immunocytochemistry and retrograde labeling were used to define the thalamic projections of calbindin- and parvalbumin-containing cells in superficial layers of the rat's superior colliculus (SC). Quantitative analysis revealed that 90.8 +/- 2.2% (mean +/- standard deviation) of the calbindin-immunoreactive neurons in the stratum griseum superficiale (SGS) projected to the dorsal lateral geniculate nucleus (LGNd) and that 91.3 +/- 4.3% of calbindin-immunoreactive neurons in the stratum opticum (SO) projected to the lateral posterior nucleus (LP). In contrast, only 17.3 +/- 2.5% of parvalbumin-immunoreactive neurons in the SGS were found to project to the LGNd and 16.5 +/- 3.1% of the parvalbumin-immunoreactive SO cells were retrogradely labeled after LP injections. Few of the parvalbumin-immunoreactive neurons in either the SGS (7.2 +/- 2.5%) or the SO (9.2 +/- 2.5%) were GABA positive. The retrograde-labeling results suggest that parvalbumin-immunoreactive neurons in the rat's SO and SGS may either be primarily interneurons or have descending projections, while calbindin-containing cells are primarily thalamic projection neurons. These results are consistent with data from other rodents, but almost exactly the opposite of data that have been reported for the cat for these same populations of SC projection neurons. Such interspecies differences raise questions regarding the functional importance of expressing one calcium-binding protein versus another in a specific neuronal population.     

Percutaneous balloon pericardiotomy for patients with recurrent pericardial effusion: using a novel double-balloon technique with one long and one short balloon

Percutaneous balloon pericardiotomy is effective and less invasive for the treatment of recurrent pericardial effusion. This study suggests that the double-balloon method with 1 longer and 1 shorter balloon is the procedure of choice for percutaneous balloon pericardiotomy.     

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy

Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease. The coexistence of autoimmune disease and hematologic malignancy provides an opportunity to examine the response of autoimmune disease to ABMT or ASCT. We describe 4 patients with autoimmune disease (3 with psoriasis and 1 with rheumatoid arthritis) and hematologic malignancy. In each patient, the autoimmune disease remitted posttransplantation, but, in 4 patients with long-term followup, it recurred at 8-24 months. The earliest relapse occurred in a patient treated with interferon-alpha. Our experience suggests that a single autograft with unpurged stem cells is unlikely to cure autoimmune disease, but that other strategies building on this approach are worthy of investigation.     

Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidaemic patients

Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different way. Fibrinogen antigen levels were elevated by 17.6% (p <0.05) and 24.3% (p <0.001) with gemfibrozil after six and twelve weeks, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional fibrinogen levels were decreased by 10.1% (p <0.001) and 10.5% (p <0.0001), respectively on the basis of Clauss mechanical and by 14.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen. Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen.