Sorocenols G and H, anti-MRSA oxygen heterocyclic Diels-Alder-type adducts from Sorocea muriculata roots.

Bioassay-guided fractionation of a root extract of Sorocea muriculata led to the isolation and identification of two new oxygen heterocyclic Diels-Alder-type adducts, sorocenols G (1) and H (2), along with lupeol-3-(3' R-hydroxytetradecanoate) and oxyresveratrol. The structures of 1 and 2 were elucidated using 1D and 2D NMR spectroscopic and HRMS data and by comparison with reported values. The absolute configurations of 1 and 2 were established by analysis of their experimental and theoretically calculated CD spectra.

Non-cannabinoid constituents from a high potency Cannabis sativa variety.

Six new non-cannabinoid constituents were isolated from a high potency Cannabis sativa L. variety, namely 5-acetoxy-6-geranyl-3-n-pentyl-1,4-benzoquinone (1), 4,5-dihydroxy-2,3,6-trimethoxy-9,10-dihydrophenanthrene (2), 4-hydroxy-2,3,6,7-tetramethoxy-9,10-dihydrophenanthrene (3), 4,7-dimethoxy-1,2,5-trihydroxyphenanthrene (4), cannflavin C (5) and beta-sitosteryl-3-O-beta-d-glucopyranoside-2'-O-palmitate (6). In addition, five known compounds, alpha-cannabispiranol (7), chrysoeriol (8), 6-prenylapigenin (9), cannflavin A (10) and beta-acetyl cannabispiranol (11) were identified, with 8 and 9 being reported for the first time from cannabis.

The impact of tyrosine kinase 2 (Tyk2) on the proteome of murine macrophages and their response to lipopolysaccharide (LPS).

Tyrosine kinase 2 (Tyk2) belongs to the Janus kinase (Jak) family and is involved in signalling via a number of cytokines. Tyk2-deficient mice are highly resistant to lipopolysaccharide (LPS)-induced endotoxin shock. Macrophages are key players in the pathogenesis of endotoxin shock and, accordingly, defects in the LPS responses of Tyk2(-/-) macrophages have been reported.

Sinulodurins A and B, antiproliferative and anti-invasive diterpenes from the soft coral Sinularia dura.

Two new diterpenes, sinulodurin A (1) and sinulodurin B (2), along with two known sterols, 24 S-methyl cholesterol and 24-methylene cholesterol, were isolated from the Palau soft coral Sinularia dura. The structures of the new metabolites were determined on the basis of spectroscopic methods and by comparison of NMR data with those of related metabolites. Sinulodurin A (1) and sinulodurin B (2) showed antiproliferative activity against highly malignant +SA mammary epithelial cells with an IC 50 range of 20-30 microM.

Neuropathological effect of carbamate molluscicides on the land snail, Eobania vermiculata.

The present study was designed to investigate the neuropathological effect of the two carbamate pesticides: methomyl and methiocarb on the neurons of the buccal ganglia in the land snail Eobania vermiculata using topical application and baiting technique. Their in vivo effects on acetylcholinesterase (AChE, EC 3.1.

Impact of comorbidity on overall survival in patients surgically treated for renal cell carcinoma.

Objectives: Although the classification of cancer has traditionally focused on the gross and microscopic characteristics of the tumor, the overall health of patients can affect their survival. Because patients with renal cell carcinoma often have other medical conditions, we explored the effect of preexisting medical disease on survival after radical and partial nephrectomy.

Methods: From January 1995 to August 2003, the comorbidity status of 697 patients with nonmetastatic renal cell carcinoma who had undergone radical or partial nephrectomy was prospectively coded using the Adult Comorbidity Evaluation-27.

Synthesis and pharmacological evaluation of 2-substituted benzo[b]thiophenes as anti-inflammatory and analgesic agents.

An efficient method for trapping isocyanate 4, generated from the Curtius rearrangement, with ethyl alcohol to afford the carbamate 5 is reported. 5-Nitrobenzo[b]thiophene-2-carboxylic acid 1 is converted to the corresponding hydrazide 2 by the reaction with hydrazine hydrate and then to the azide 3 with nitrous acid, followed by thermal rearrangement, cooling, and trapping in one pot reaction. The carbamate 5 is treated with hydrazine hydrate to afford the desired, Zileuton analogue, 4-(5-nitrobenzo[b]thiophene-2-yl)semicarbazide 6.

The differences in RCAS1 and DFF45 endometrial expression between late proliferative, early secretory, and mid-secretory cycle phases.

RCAS1 expression is related to the regulation of activated immune cells and to connective tissue remodeling within the endometrium. DFF45 seems to play an important role in the apoptotic process, most likely by acting through the regulation of DNA fragmentation. Its expression changes within the endometrium seem to be related to the resistance of endometrial cells to apoptosis.

Cannabinoid ester constituents from high-potency Cannabis sativa.

Eleven new cannabinoid esters, together with three known cannabinoid acids and Delta9-tetrahydrocannabinol ( Delta9-THC ), were isolated from a high-potency variety of Cannabis sativa. The structures were determined by extensive spectroscopic analyses to be beta-fenchyl Delta9-tetrahydrocannabinolate ( 1), epi-bornyl Delta9-tetrahydrocannabinolate ( 2), alpha-terpenyl Delta9-tetrahydrocannabinolate ( 3), 4-terpenyl Delta 9-tetrahydrocannabinolate ( 4), alpha-cadinyl Delta9-tetrahydrocannabinolate ( 5), gamma-eudesmyl Delta9-tetrahydrocannabinolate ( 6), gamma-eudesmyl cannabigerolate ( 7), 4-terpenyl cannabinolate ( 8), bornyl Delta9-tetrahydrocannabinolate ( 9), alpha-fenchyl Delta9-tetrahydrocannabinolate ( 10), alpha-cadinyl cannabigerolate ( 11), Delta9-tetrahydrocannabinol ( Delta9-THC ), Delta9-tetrahydrocannabinolic acid A ( Delta9-THCA ), cannabinolic acid A ( CBNA), and cannabigerolic acid ( CBGA). Compound 8 showed moderate antimicrobial activity against Candida albicans ATCC 90028 with an IC 50 value of 8.

Isolation and characterization of new Cannabis constituents from a high potency variety.

Phytochemical investigation of a high potency variety of Cannabis sativa L. resulted in the isolation of six new metabolites, (+/-)-6,7-trans-epoxycannabigerolic acid ( 2), (+/-)-6,7- CIS-epoxycannabigerolic acid ( 3), (+/-)-6,7- CIS-epoxycannabigerol ( 4), (+/-)-6,7-trans-epoxycannabigerol ( 5), 5'-methyl-4-pentylbiphenyl-2,2',6-triol ( 7), and 7-methoxycannabispirone ( 8), along with seven known compounds namely, cannabigerolic acid ( 1), 5'-methoxycannabigerolic acid ( 6), cannabispirone ( 9), beta-cannabispiranol ( 10), dehydrocannabifuran ( 11), cannflavin B ( 12) and cannabigerol ( 13). The antimicrobial as well as the antileishmanial activities were investigated.

Is human placenta proteoglycan remodeling involved in pre-eclampsia?

Impaired placento-fetal communication is a coherent symptom of exaggerated pre-eclampsia. The impact of the cellular expression of different glycosaminoglycans (GAGs) in this event on the placenta in pre-eclampsia is still obscure. This is the first study aimed at discovering the relationship between structural alterations of different sulfated GAGs at the molecular level and the development of pre-eclampsia in inflicted placenta.

Prognostic impact of comorbidity in patients with bladder cancer.

Objective: To determine the impact of comorbidity on survival of bladder cancer patients.

Methods: The population included 675 patients with newly diagnosed bladder cancer whose medical information was abstracted from a hospital cancer registry. Adult Comorbidity Evaluation-27, a validated instrument, was used to prospectively categorize comorbidity.

The role of T-regulatory cells in pregnancy and cancer.

The acceptance of paternally-derived alloantigens during pregnancy and escape from host immunosurveillance by cancer are based on similar immunological mechanisms. Among them both natural and peripherally-induced T CD4+ CD25+ Foxp3+ and Tr1 regulatory cells (Tregs) play important role. Interactions of Tregs with other immunocytes including dendritic cells, mechanisms of Tregs recruitment and their suppressive properties in cancer and pregnancy have been presented in this paper.

The characterization and role of regulatory T cells in immune reactions.

Regulatory T cells (Tregs) having CD4+ CD25+ Foxp3+ or CD4+ IL-10+ (Tr1) phenotype and capable of inducing anergy towards self- and alloantigens play an important role in autoimmunity, as well as in tolerance of allografts, pregnancy and cancer. Both thymus-derived T CD4+ CD25+ Foxp3+ natural cells and peripherally-induced T CD4+ CD25+ Foxp3+ cells prevent migration of effector immunocytes to target organs and inhibit their cooperation with antigen-presenting cells. The suppressive function of CD4+ CD25+ Foxp3+ Tregs depends on interactions between stimulatory (IL-2, CTLA-4) and inhibitory (GITR, CD28) signals, on stimulation of indoleamine 2,3-dioxygenase (IDO) activity in dendritic cells via CD80/CD86 molecules, and finally on cell-cell inhibition of effector cells by membrane-bound TGF-beta.

Potential of some monoterpenoids and their new N-methyl carbamate derivatives against Schistosomiasis snail vector, Biomphalaria alexandrina.

Some monoterpenoids and their corresponding new N-methyl carbamate derivatives were used to study their molluscicidal effect on Biomphalaria alexandrina, the snail-vector of Schistosoma mansoni in Egypt. Improving the efficacy of the tested monoterpenoids and/or their corresponding carbamates by either piperonyl butoxide (PBO) or triton X-100 (TX) was also performed. Thymol, β-citronellol, carvacrol, and geraniol exhibited high molluscicidal activity against the snails.

Soil amendment with dried weed leaves as non-chemical approach for the management of Meloidogyne incognita infecting tomato.

In pot trial, dried ground weed leaves of Cynodon dactylon, Datura stramonium, Eichhomia crassipes, Emex spinosus, Ricinus communis and Sisymbrium irio were mixed with soil at the rate of 1, 3, 5 and 10 g/kg soil and compared their nematicidal potential with carbofuran as a standard against the root-knot nematode, M. incognita infecting tomato. In addition, their effects on growth rate of tomato plants were also investigated.

Botulinum toxin treatment for anal fissure.

Objectives: To evaluate the effectiveness of Botulinum toxin injection in the treatment of anal fissure.

Methods: 38 patients (22 males, 16 females; mean age (SD) of 33.3 (8.

Prostate-specific antigen density predicts adverse pathology and increased risk of biochemical failure.

Objectives: To determine whether the prostate-specific antigen (PSA) density (PSAD), measured using either ultrasound (US) or prostatic weight (PW), is an independent predictor of adverse pathologic findings or biochemical-free survival and whether it outperformed PSA.

Methods: The data were obtained prospectively from 1327 patients undergoing radical prostatectomy from 1990 to 2003. The US PSAD was calculated by dividing the preoperative PSA level in nanograms per milliliter by the US measured prostate volume in cubic centimeters.

The effect of chronic cadmium exposure on the pharmacokinetics of theophylline and ciprofloxacin in rats.

Cadmium has been associated with a number of adverse health effects but the impact of those effects on the pharmacokinetics of different drugs has not been investigated. Therefore, the pharmacokinetics of theophylline and ciprofloxacin were studied in cadmium-exposed and control rats (72 rats) following i.p.

Synthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatory and analgesic agents.

Treatment of 3-cyanoacetyl indole 1 with the diazonium salts of 3-phenyl-5-aminopyrazole and 2-aminobenzimidazole afforded the corresponding hydrazones 4 and 5. 3-Cyanoacetyl indole reacted with phenylisothiocyanate to give the corresponding thioacetanilide derivative 7. Treatment of 7 with hydrazonoyl chlorides afforded the corresponding 1,3,4-thiadiazole derivatives 8a-f and 9.

The effects of induced diabetes and cutaneous Leishmania infection on the pharmacokinetics of antimony in hamsters.

Patients with certain diseases appear to be at greater risk of developing adverse drug interactions, either because of the disease state itself or the drugs used to treat it. The effects of streptozotocin-induced diabetes and/or cutaneous Leishmania major infection on the pharmacokinetics of antimony (SbV) have now been investigated, in hamsters treated with sodium stibogluconate (Pentostam). The animals were randomly divided into five groups, each of 20 hamsters, known as D (for diabetes without leishmaniasis), DL (diabetes induced prior to the leishmaniasis), L (leishmaniasis without diabetes), LD (diabetes induced after leishmanial infection) and C (the control group, of animals with neither diabetes nor leishmaniasis).

Comparison of reactive oxygen species concentration in seminal plasma and semen parameters in partners of pregnant and non-pregnant patients after IVF/ICSI.

The aims of this study were (i) to determine and compare the concentration of reactive oxygen species (ROS) and total antioxidant status (TAS) in seminal plasma and sperm parameters of the male partners of patients undergoing IVF or intracytoplasmic sperm injection (ICSI) treatment and (ii) to establish the relationship between ROS and TAS concentrations and sperm quality and their effect on fertilization and pregnancy rate of patients who achieved a pregnancy and those who were unsuccessful. Twenty-six IVF and 22 ICSI patients were included in this study. The ROS concentration in seminal plasma and sperm concentration, vitality (eosin test), motility, morphology, membrane integrity (HOS test), maturity (chromomycin, CMA3) and DNA fragmentation (TUNEL) results and their relationship to fertilization and pregnancy were analysed.

Synthesis and antitumor activity of indolylpyrimidines: marine natural product meridianin D analogues.

Marine indole alkaloid meridianin D analogues have been synthesized starting from the appropriate 3-cyanoacetyl indole. A facile two-step conversion of 3-cyanoacetyl indole to the corresponding cyano meridianin D analogue by treatment with dimethylformamide-dimethylacetal and further cyclization of the resulting enaminonitrile with aminoguanidine is described. Then, alkaline hydrolysis of cyano meridianin D afforded the carboxylic acid analogue.