Topical delivery of fluconazole: in vitro skin penetration and permeation using emulsions as dosage forms.

We investigated in vitro skin penetration and permeation of fluconazole from emulsions containing different penetration enhancers. Fluconazole permeation was high (15-65% of the applied dose) across hairless mouse skin and low (8-9%) across pig ear skin. Permeation across mice skin from a formulation containing propyleneglycol and isopropyl myristate was significantly higher than that observed with the paraffin oil and propyleneglycol or Transcutol emulsions.

Gene expression profiling in melanoma identifies novel downstream effectors of p14ARF.

p14ARF is inactivated by deletions/mutations in many cancer types and can suppress cell growth by both p53-dependent and p53-independent mechanisms. To identify novel downstream effectors of p14ARF, we used gene expression profiling as a primary screening tool to select candidates for follow up validation studies using in vitro cell-based assays. Gene expression profiles of a panel of 35 melanoma cell lines with either wild-type (n = 12) or mutant (n = 23) p14ARF were compared to identify genes associated with inactivation of p14ARF.

Physical and functional interaction of the p14ARF tumor suppressor with ribosomes.

Alterations in the p14(ARF) tumor suppressor are frequent in many human cancers and are associated with susceptibility to melanoma, pancreatic cancer, and nervous system tumors. In addition to its p53-regulatory functions, p14(ARF) has been shown to influence ribosome biogenesis and to regulate the endoribonuclease B23, but there remains considerable controversy about its nucleolar role. We sought to clarify the activities of p14(ARF) by studying its interaction with ribosomes.

Role of the calcarine cortex (V1) in perception of visual cues for saccades.

Objective: To determine the initial level at which the pathways for cue perception, saccades and antisaccades diverge.

Methods: Two procedures: single pulse transcranial magnetic stimulation (sTMS) over posterior occiput and backward masking were used. A visual cue directed saccades to the left or right, either a pro-saccade (to the side of the cue but beyond it) or an antisaccade, i.

The melanoma-associated 24 base pair duplication in p16INK4a is functionally impaired.

Melanoma-associated germline mutations affecting the tumor suppressor and cyclin-dependent kinase (CDK) inhibitor, CDKN2A/p16INK4a, have been identified in over 100 melanoma-prone families worldwide. To predict the melanoma risk for carriers of specific mutations, mutant p16INK4a can be tested in biochemical and cellular assays. In most cases, p16INK4a mutations with predicted disease relation, due to segregation with melanoma, are functionally impaired in such assays.

Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes.

Background: Bone marrow stromal cells (BMSCs) have the potential to differentiate into various cells and can transdifferentiate into myocytes if an appropriate cellular environment is provided. However, the molecular signals that underlie this process are not fully understood. In this study, we show that BMSC differentiation is dependent on communication with cells in their microenvironment.

Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart.

Myocardial infarction may cause sudden cardiac death and heart failure. Adult cardiac myocytes do not replicate due to lack of a substantive pool of precursor, stem, or reserve cells in an adult heart. Ventricular myocytes following myocardial infarction are replaced by fibrous tissue and this leads to congestive heart failure in severe cases.

Adenosine A(1) receptor mediates late preconditioning via activation of PKC-delta signaling pathway.

Protein kinase C (PKC) plays a central role in both early and late preconditioning (PC) but its association with inducible nitric oxide synthase (iNOS) is not clear in late PC. This study investigates the PKC signaling pathway in the late PC induced by activation of adenosine A(1) receptor (A(1)R) with adenosine agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) and the effect on iNOS upregulation. Adult male mice were pretreated with saline or CCPA (100 microg/kg iv) or CCPA (100 microg/kg iv) with PKC-delta inhibitor rottlerin (50 microg/kg ip).

Mitochondrial K(ATP) channel as an end effector of cardioprotection during late preconditioning: triggering role of nitric oxide.

Nitric oxide (NO) has been implicated in the "second-window" of ischemic preconditioning (PC). However, the identity of the end effector after initiation of preconditioning by NO is not known. It is likely that NO is involved in opening of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels.

Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential.

Mitochondrial membrane potential (DeltaPsi(m)) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel activation prevents the collapse of DeltaPsi(m) in myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration.

Downregulation of protein kinase C inhibits activation of mitochondrial K(ATP) channels by diazoxide.

Background: The mitochondrial K(ATP) (mitoK(ATP)) channel has been shown to confer short- and long-term cardioprotection against prolonged ischemia via protein kinase C (PKC) signaling pathways. However, the exact association between PKC or its isoforms and mitoK(ATP) channels has not yet been clarified. The present study tested the hypothesis that the activity and translocation of PKC to the mitochondria are important for cardiac protection elicited by mitoK(ATP) channels.

Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis.

We tested the hypothesis whether calcium preconditioning (CPC) reduces reoxygenation injury by inhibiting mitochondrial permeability transition (MPT). Cultured myocytes were preconditioned by a brief exposure to 1.5 mM calcium (CPC) and subjected to 3 h of anoxia followed by 2 h of reoxygenation (A-R).

Low serum paraoxonase: a risk factor for atherosclerotic disease?

Serum paraoxonase (PON1) hydrolyses organophosphate (OP) insecticides and nerve gases and is responsible for determining the selective toxicity of these compounds in mammals. PON1 has two genetic polymorphisms giving rise to amino acid substitutions at position 55 and 192. The 192 polymorphism is the major determinant of the PON1 activity polymorphism towards organophosphates.

Serum paraoxonase after myocardial infarction.

HDL has been shown to prevent the oxidative modification of LDL. The antioxidant activity of HDL is believed to reside in its enzymes, particularly paraoxonase. Human serum paraoxonase (PON1) is closely associated with a specific HDL subfraction also containing apoA1 and clusterin.

Idiopathic chronic active hepatitis: a diagnostic and therapeutic dilemma.

A 56-year-old Saudi male was admitted with abnormal liver chemistry values and a > 5-month history of lethargy, malaise, anorexia, and jaundice. Extensive investigations did not establish an etiological diagnosis. Liver histology confirmed the clinically apparent aggressive hepatitis with fibrosis but gave no clue to its etiology.

Preoperatory treatment with Triptorelin LA in hysteroscopic metroplastic.

Septate uterus is the intracavitary pathology which is most associated with infertility and/or preterm labor; therefore, it is primary indication for hysteroscopic metroplasty. By the introductio of the resectoscope in gynaecological endoscopy the surgical technique has been revolutioned. GnRHa therapy before surgery has showed some advantages related to surgical results, surgery time, intraoperative bleeding and endometrial detachment, and amount of fluids used for uterine cavity distention.

Anti-Brucella activity of Ro 23-9424, a dual-action antibacterial.

The in vitro activity of dual-acting antibacterial Ro 23-9424 was determined by the agar dilution method against 126 clinical isolates of Brucella melitensis. It was compared with fleroxacin, ciprofloxacin and five conventional drugs. MIC50 and MIC90 for Ro 23-9424 were 1.

Histologically advanced chronic hepatitis C treated with recombinant alpha-interferon: a randomized placebo-controlled double-blind cross-over study.

Chronic hepatitis C is common in Saudi Arabia and most often presents in an advanced stage. To assess the response of patients to interferon, a randomized placebo-controlled double-blind study was undertaken. All but 1 patient had cirrhosis or fibrosis before interferon.

Susceptibility of Salmonella typhi and Brucella melitensis to the new fluoroquinolone rufloxacin (MF 934).

The antimicrobial activity of the new fluoroquinolone rufloxacin (MF 934) was evaluated by a standardized agar dilution method against recent clinical isolates of Salmonella typhi (67 strains) and Brucella melitensis (108 isolates). The results were compared with 5 other commercially available or investigational fluoroquinolones. All the isolates of S.

Brucella peritonitis.

We report the case of a patient with peritonitis caused by Brucella melitensis who also had chronic liver disease. At first the patient was treated for bacterial peritonitis but when a lymphocytic ascites was aspirated antituberculosis chemotherapy was given. However, the serological tests for brucellosis were strongly positive and subsequently B.