Effect of linkage of transduction domain sequences to a lymphoma idiotype DNA vaccine on vaccine effectiveness

Patient idiotype-specific vaccines for treatment of non-Hodgkin's lymphoma have shown promise in clinical trials, encouraging efforts to enhance the effectiveness of idiotype vaccines further. It has previously been found that for some other types of experimental vaccines, the addition of transduction domains has improved vaccine immunogenicity. Transduction domains are short amino acid sequences that are capable of increasing transport through cellular membranes. In this study, we tested murine B cell 38C13 lymphoma idiotype DNA vaccines with human immunodeficiency virus (HIV) Tat-derived transduction sequences for efficacy against 38C13 challenge. The rate of tumor onset was similar for the idiotype and transduction domain-conjugated idiotype vaccine groups. At days 22-23 postchallenge, the number of surviving mice was significantly higher in the group that had received a DNA vaccine consisting of the 38C13 idiotype sequence plus modified Tat transduction sequence, in comparison with the group that received idiotype-only vaccines. Although the overall survival difference was not statistically significant following day 24, a trend toward an increased survival rate for mice receiving idiotype plus Tat-derived transduction domains was maintained through day 106 postchallenge. Thus, the addition to idiotype vaccines of specific sequences that facilitate intracellular transport may have potential to improve the effectiveness of such vaccines.     

Influence of Temik (Aldicarb) on herbicide persistence in cultivated cotton field soil under field conditions

Summary The effect of the insecticide Temik on the persistence of the herbicides Cotoran and Cobex was investigated in cultivated cotton fields. Temik was applied to the soil which had also been treated with Gotoran or Cobex. Residues were determined at 15 day-intervals for four months. Temik was found to inhibit the degradation of both compounds as long as it persisted. As Temik disappeared the degradation of Cotoran and Cobex increased, attaining after the 15th day the rates shown by Cotoran and Cobex when applied in isolation.     

Masson's vegetant intravascular hemangioendothelioma in an external jugular vein aneurysm with recurrent thrombosis

A 50-year-old male patient was admitted for a symptomatic aneurysm of the external jugular vein. Thrombosis of the aneurysm was treated by oral anticoagulant but recurrence of neck swelling and thrombosis occurred 1 year after oral anticoagulant was discontinued. No other vascular anomalies were detected, and blood tests were normal. Surgical resection was done "en bloc" with the muscular fibers in contact. Pathologic examination was compatible with a Masson's vegetant intravascular hemangioendothelioma. To our knowledge, this is the first case of symptomatic Masson's vegetant intravascular hemangioendothelioma diagnosed in a patient with thrombosed aneurysm of a cervical vein.     

Synthesis of some novel substituted purine derivatives as potential anticancer, anti-HIV-1 and antimicrobial agents

In search of novel purine antimetabolites, a series of 8-substituted methylxanthine derivatives was prepared in order to explore their in vitro anticancer, anti-HIV-1 and antimicrobial activities. The target compounds include: 8-[(3-substituted-4-oxo-thiazolidin-2-ylidene)hydrazino]-1,3-dimethyl (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 5a-e, 8-[(3,4-disubstituted 2,3-dihydrothiazol-2-ylidene)hydrazino]-1,3,7-trimethyl-3,7-dihydropurine-2,6-diones 6a-d and 8-(5-amino-3-arylpyrazol-1-yl)-1,3-dimethyl- (or 1,3,7-trimethyl)-3,7-dihydropurine-2,6-diones 7a-g. The in vitro anticancer results revealed that compound 5d exhibited a super sensitivity profile towards leukemia K-562 with a GI(50) value of <0.01 microM. Compound 7c showed significant activity against colon cancer HCT-15 and renal cancer CAKI-1 (GI(50) values of 0.47 and 0.78 microM, respectively). Compound 7a displayed high activity against colon cancer HCT-15 (GI(50 )= 0.8 microM). The anti-HIV-1 results indicated that compound 6b displayed a good reduction of viral cytopathic effect (56.69%). The antimicrobial results showed that compound 5a was four times more active than ampicillin against P. aerugenosa (MIC =or< 25 microg/mL), compound 5b had twice the activity of ampicillin, while compounds 5d, 7c and 7f were equipotent to ampicillin. On the other hand, compound 7a was equipotent to ampicillin against P. vulgaris (MIC = 50 microg/mL).     

Biological activity of the essential oil of Kadsura longipedunculata (Schisandraceae) and its major components

Objectives The aim was to determine the chemical composition of the essential oil of Kadsura longipedunculata and the biological activity of the oil and its major components. Methods The essential oil from stem bark of Kadsura longipedunculata was analysed by capillary gas chromatography (GLC/FID) and gas chromatography–mass spectrometry (GLC/MS). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH^?) was used to evaluate the antioxidant activity. Inhibition of both lipoxygenase and prostaglandin E₂ was used to assess the anti‐inflammatory activity. Antimicrobial activity was studied in vitro against a range of bacteria and fungi using diffusion and microdilution methods. Inhibition of trypanosome proliferation was assessed using resazurin as vital stain. The in‐vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, MIA PaCa‐2, HeLa, HL‐60, MDA‐MB‐231 and SW‐480) was examined using the MTT assay. Key findings Fifty compounds, representing 97.63% of total oil, were identified. δ‐Cadinene (21.79%), camphene (7.27%), borneol (6.05%), cubenol (5.12%) and δ‐cadinol (5.11%) were found to be the major components of the oil. The oil exerted a good antimicrobial activity against all Gram‐positive bacteria tested, including methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant Enterococcus faecalis. Streptococcus pyogenes and S. agalactiae were the most sensitive bacteria with a minimal inhibitory concentration (MIC) of 60 µg/ml oil. The essential oil showed a moderate fungicidal activity against yeasts, but it did not show any activity against Gram‐negative bacteria. The essential oil showed a good trypanocidal activity in Trypanosoma b. brucei with an IC50 value of 50.52 ± 0.029 µg/ml. Radical scavenging activity had an IC50 value of 3.06 ± 0.79 mg/ml. 5‐Lipoxygenase inhibition (IC50 = 38.58 µg/ml) and prostaglandin E₂ production inhibition (28.82% at 25 µg/ml) accounted for anti‐inflammatory activity of the oil. The oil exhibited some degree of cytotoxic activity against MIA PaCa‐2, HepG‐2 and SW‐480 cell lines with IC50 values of 133.53, 136.96 and 136.62 µg/ml, respectively. The oil increased caspase 3/7 activity (an indicator of apoptosis) 2.5–4 fold in MIA Paca‐2 cells. Camphene and borneol did not show antioxidant activity. However, both compounds exhibited some degree of antimicrobial, trypanocidal, anti‐inflammatory and cytotoxic activity. Conclusions This investigation provided evidence for, and confirmed the efficacy of, K. longipedunculata, a traditionally used Chinese medicinal plant for the treatment of inflammation and infection.     

Mechanisms of the antihyperglycemic activity of Retama raetam in streptozotocin-induced diabetic rats

Retama raetam (RR) fruits are used in Saudi traditional medicine for the treatment of diabetes. Current study aimed at evaluating the potential and mechanisms of the antidiabetic activity of the RR methanolic extract in streptozotocin-induced diabetic rats. Oral LD₅₀ of the extract was found to be 1995 mg/kg. The extract was administered once orally to STZ-diabetic rats at three dose levels; 100, 250 or 500 mg/kg/day for 4 consecutive weeks. RR extract at 250 or 500 mg/kg significantly lowered blood glucose levels at the 3rd and 1st week of treatment, respectively. Meanwhile, oral glucose tolerance test indicated that the same two doses significantly lowered glucose levels at 30 and 60 min after glucose challenge. Administration of RR extract at 500 mg/kg/day for 4 consecutive weeks significantly increased serum insulin level. In vitro studies indicated that the extract significantly inhibits glucose absorption by rat isolated intestine. The extract neither altered glucose uptake by rat isolated psoas muscle nor the activity of hepatic microsomal glucose-6-phosphatase. In conclusion, the methanolic extract of RR improves STZ-induced diabetes in rats. This can be attributed, at least partly, to stimulating pancreatic insulin release and reducing intestinal glucose absorption.     

Cranberry (Vaccinium macrocarpon) protects against doxorubicin-induced cardiotoxicity in rats

Doxorubicin (DOX) is a widely used cancer chemotherapeutic agent. However, it generates free oxygen radicals that result in serious dose-limiting cardiotoxicity. Supplementations with berries were proven effective in reducing oxidative stress associated with several ailments. The aim of the current study was to investigate the potential protective effect of cranberry extract (CRAN) against DOX-induced cardiotoxicity in rats. CRAN was given orally to rats (100 mg/kg/day for 10 consecutive days) and DOX (15 mg/kg; i.p.) was administered on the seventh day. CRAN protected against DOX-induced increased mortality and ECG changes. It significantly inhibited DOX-provoked glutathione (GSH) depletion and accumulation of oxidized glutathione (GSSG), malondialdehyde (MDA), and protein carbonyls in cardiac tissues. The reductions of cardiac activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were significantly mitigated. Elevation of cardiac myeloperoxidase (MPO) activity in response to DOX treatment was significantly hampered. Pretreatment of CRAN significantly guarded against DOX-induced rise of serum lactate dehydrogenase (LDH), creatine phosphokinase (CK), creatine kinase-MB (CK-MB) as well as troponin I level. CRAN alleviated histopathological changes in rats’ hearts treated with DOX. In conclusion, CRAN protects against DOX-induced cardiotoxicity in rats. This can be attributed, at least in part, to CRAN’s antioxidant activity.     

Modulation of Th1 cytokines and inflammatory mediators by Euphorbia hirta in animal model of adjuvant-induced arthritis

Euphorbia hirta L. (Euphorbiaceae) (E. hirta) is a tree locally used as a traditional medicine in Africa and Australia to treat numerous diseases such as hypertension, respiratory ailments, tumors, antipyretic, anti-inflammatory activities. In the present study, we investigated the anti-arthritic activity of fresh leaves of E. hirta ethanol extract that was found to inhibit the production of inflammatory mediators and cytokines of adjuvant arthritis in rats. Adjuvant arthritis was induced in rats (Wistar) by the subplantar injection of 0.05 ml freshly prepared suspension (5.0 mg/ml) of steam killed Mycobacterium tuberculli in liquid paraffin. Animals were treated with graded doses of 25, 50, 100 and 200 mg/kg of E. hirta ethanol extract, p.o. E. hirta significantly inhibited the swelling of the adjuvant-induced arthritis. Moreover, E. hirta at higher dose (200 mg/kg) showed 40.54 ± 1.09 % of CD3+, 15.1 ± 0.76 % of CD4+, 12.2 ± 1.18 % of CD8+ T cell receptor and 17.6 ± 1.11 % gated of CD19+ B cell receptor revealing a down regulation of adjuvant-induced arthritis as compared to the corresponding valves of the arthritic control rats. According to the results shown in Tables 1, 2, the production of IL-1β, TNF-α, IL-2 and IFN-γ were increased in splenocytes of arthritic rats and this increased level was reduced by E. hirta. Also, E. hirta significantly down regulated lipopolysaccharide (LPS)-induced production of nitric oxide production in peritoneal macrophages. These results suggest that E. hirta exhibits an improvement in adjuvant-induced arthritis through down regulation of activated macrophages and T lymphocytes functions. Such unique effects of E. hirta shown on adjuvant arthritis rat model may be advantageous to the long-term treatment of clinical rheumatoid arthritis.