Stevens’ Cure (Umckaloabo)—the vindication of a patent medicine

Stevens’ Cure (Umckaloabo) emerged as a patent medicine claiming to treat tuberculosis in the United Kingdom at the beginning of the 20th century. However, due to its identity being shrouded in secrecy, it was never truly accepted by the medical community. It was “rediscovered” in the 1970s and subsequently developed into a very popular and successful phytopharmaceutical for the treatment of upper respiratory tract infections. Whether Stevens’ Cure contained the same ingredient(s) as the modern Umckaloabo has not yet been demonstrated. We attempted to elucidate for the first time the identity of the original ingredient by comparative analysis of historical product samples. Three historical samples of Stevens’ Cure were compared with Pelargonium sidoides DC. and P. reniforme Curt. root per UPLC-MS analysis. We confirm that the ingredient–P. sidoides DC.—is indeed the same as used in modern phytotherapy. We also attribute the first ethnopharmacological record of P. sidoides DC. being used for the treatment of tuberculosis to C. H. Stevens, the “creator” of Umckaloabo

Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

Abstract We have examined whether Ad.sT?RFc and TAd.sT?RFc, two oncolytic viruses expressing soluble transforming growth factor-? receptor II fused with human Fc (sTGF?RIIFc), can be developed to treat bone metastasis of prostate cancer. Incubation of PC-3 and DU-145 prostate tumor cells with Ad.sT?RFc and TAd.sT?RFc produced sTGF?RIIFc and viral replication; sTGF?RIIFc caused inhibition of TGF-?-mediated SMAD2 and SMAD3 phosphorylation. Ad(E1-).sT?RFc, an E1? adenovirus, produced sTGF?RIIFc but failed to replicate in tumor cells. To examine the antitumor response of adenoviral vectors, PC-3-luc cells were injected into the left heart ventricle of nude mice. On day 9, mice were subjected to whole-body bioluminescence imaging (BLI). Mice bearing hind-limb tumors were administered viral vectors via the tail vein on days 10, 13, and 17 (2.5?1010 viral particles per injection per mouse, each injection in a 0.1-ml volume), and subjected to BLI and X-ray radiography weekly until day 53. Ad.sT?RFc, TAd.sT?RFc, and Ad(E1-).sT?RFc caused significant inhibition of tumor growth; however, Ad.sT?RFc was the most effective among all the vectors. Only Ad.sT?RFc and TAd.sT?RFc inhibited tumor-induced hypercalcemia. Histomorphometric and synchrotron micro-computed tomographic analysis of isolated bones indicated that Ad.sT?RFc induced significant reduction in tumor burden, osteoclast number, and trabecular and cortical bone destruction. These studies suggest that Ad.sT?RFc and TAd.sT?RFc can be developed as potential new therapies for prostate cancer bone metastasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98454/1/hum%2E2012%2E040.pd

Correlation of cutaneous tension distribution and tissue oxygenation with acute external tissue expansion

Today, the biomechanical fundamentals of skin expansion are based on viscoelastic models of the skin. Although many studies have been conducted in vitro, analyses performed in vivo are rare. Here, we present in vivo measurements of the expansion at the skin surface as well as measurement of the corresponding intracutaneous oxygen partial pressure. In our study the average skin stretching was 24%, with a standard deviation of 11%, excluding age or gender dependency. The measurement of intracutaneous oxygen partial pressure produced strong inter-individual fluctuations, including initial values at the beginning of the measurement, as well as varying individual patient reactions to expansion of the skin. Taken together, we propose that even large defect wounds can be closed successfully using the mass displacement caused by expansion especially in areas where soft, voluminous tissue layers are present

Genotoxic potential of Cotinus coggygria Scop. (Anacardiaceae) stem extract in vivo

The intention was to evaluate the possible in vivo genotoxic potential in different cell-types, of a methanol extract obtained from the plant stem of Cotinus coggygria Scop., using the sex-linked recessive lethal (or SLRL) test and alkaline comet assay. The SLRL test, revealed the genotoxic effect of this extract in postmeiotic and premeiotic germ-cell lines. The comet assay was carried out on rat liver and bone marrow at 24 and 72 h after intraperitoneal administration. For genotoxic evaluation, three concentrations of the extract were tested, viz., 500, 1000 and 2000 mg/kg body weight (bw), based on the solubility limit of the extract in saline. Comet tail moment and total scores in the group treated with 500 mg/kg bw, 24 and 72 h after treatment, were not significantly different from the control group, whereas in the groups of animals, under the same conditions, but with 1000 and 2000 mg/kg bw of the extract, scores were statistically so. A slight decrease in the comet score and tail moment observed in all the doses in the 72 h treatment, gave to understand that DNA damage induced by Cotinus coggygria extract decreased with time. The results of both tests revealed the genotoxic effect of Cotinus coggygria under our experimental conditions

Three independently deleted regions at chromosome arm 16q in human prostate cancer: allelic loss at 16q24.1–q24.2 is associated with aggressive behaviour of the disease, recurrent growth, poor differentiation of the tumour and poor prognosis for the patient

Loss of heterozygosity at chromosome arm 16q is a frequent event in human prostate cancer. In this study, loss of heterozygosity at 16q was studied in 44 prostate cancer patients exhibiting various clinical features. Fifteen polymorphic polymerase chain reaction (PCR) markers were used to identify the separately deleted areas and the findings were compared with clinicopathological variables and 5-year survival of the patients. The results indicated that there are at least three independently deleted regions at 16q. Allelic losses at the central and distal areas were associated significantly with aggressive behaviour of the disease (16q24.1–q24.2, P< 0.01, and 16q24.3–qter, P< 0.05), and the central area of deletion was further significantly associated with poorly differentiated tumour cells (P< 0.05) and with recurrent (P< 0.01) growth of the tumour. During the follow-up period, 28% of the patients initially with M0 disease developed distant metastases. Of the patients showing allelic loss at 16q24.1–q24.2, distant metastasis were found in 45% during the 5-year follow-up period, and 31% of the patients showing loss at 16q21.1 also developed distant metastases. After the 5-year follow-up period, 14 (32%) of the patients remained alive, whereas 19 (43%) had died because of their prostate cancer. The overall survival rate of the patients showing allelic loss at 16q21.1 or 16q24.1–q24.2 was significantly lower than that of the patients with retained heterozygosity. © 1999 Cancer Research Campaig

Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant

<p>Abstract</p> <p>Background</p> <p>The results of a cross-sectional study aimed to evaluate whether genetic polymorphisms (biomarkers of susceptibility) for <it>CYP1A1</it>, <it>EPHX </it>and <it>GSTM1 </it>genes that affect polycyclic aromatic hydrocarbons (PAH) activation and detoxification might influence the extent of primary DNA damage (biomarker of biologically effective dose) in PAH exposed workers are presented. PAH-exposure of the study populations was assessed by determining the concentration of 1-hydroxypyrene (1OHP) in urine samples (biomarker of exposure dose).</p> <p>Methods</p> <p>The exposed group consisted of workers (n = 109) at a graphite electrode manufacturing plant, occupationally exposed to PAH. Urinary 1OHP was measured by HPLC. Primary DNA damage was evaluated by the alkaline comet assay in peripheral blood leukocytes. Genetic polymorphisms for <it>CYP1A1</it>, <it>EPHX</it> and <it>GSTM1</it> were determined by PCR or PCR/RFLP analysis.</p> <p>Results</p> <p>1OHP and primary DNA damage were significantly higher in electrode workers compared to reference subjects. Moreover, categorization of subjects as normal or outlier highlighted an increased genotoxic risk OR = 2.59 (CI95% 1.32–5.05) associated to exposure to PAH. Polymorphisms in <it>EPHX</it> exons 3 and 4 was associated to higher urinary concentrations of 1OHP, whereas none of the genotypes analyzed (<it>CYP1A1</it>, <it>EPHX</it>, and <it>GSTM1</it>) had any significant influence on primary DNA damage as evaluated by the comet assay.</p> <p>Conclusion</p> <p>The outcomes of the present study show that molecular epidemiology approaches (i.e. cross-sectional studies of genotoxicity biomarkers) can play a role in identifying common genetic risk factors, also attempting to associate the effects with measured exposure data. Moreover, categorization of subjects as normal or outlier allowed the evaluation of the association between occupational exposure to PAH and DNA damage highlighting an increased genotoxic risk.</p

Synthesis of macrocyclic receptors with intrinsic fluorescence featuring quinizarin moieties

An unprecedented class of macrocycles with intrinsic fluorescence consisting of phenolic trimers and quinizarin is developed. Though they are lacking strong hydrogen bonds as observed in calixarenes, the two examples introduced here each adopt a vase-like conformation with all four aromatic units pointing in one direction (syn orientation). This “cone” conformation has been confirmed by NMR spectroscopy, molecular modeling, and X-ray crystallography. The laminar, electron-rich fluorophore as part of the macrocycle allows additional contacts to enclosed guest molecules