Eccrine angiomatous hamartoma causing walking difficulties

Eccrine angiomatous hamartoma (EAH) is a rare tumoral lesion that consists of vascular and eccrine malformation and often occurs in the distal extremities of children. Although EAH is benign, a therapeutic excision may be required for symptomatic or cosmetic considerations. We hereby report a typical case of EAH presenting as a painful and rapidly growing plaque on the right thigh. The associated symptoms of pain, hyperhidrosis and local hypertrichosis caused walking difficulties until the patient was cured by two excisional surgeries.     

Development of systemic immunologic responses against hepatic metastases during gene therapy for peritoneal carcinomatosis with retroviral HS-tk and ganciclovir

Gene therapy with retroviral mediated gene transfer of the herpes simplex thymidine kinase (HS-tk) gene into a tumor mass confers sensitivity of the tumor cells to ganciclovir (GCV). Tumor-specific immunologic responses may develop following treatment of the primary tumor with retroviral HS-tk and GCV. In the present study we assessed whether GCV treatment of HS-tk transduced colon cancer (TK⁺) implanted in the peritoneal cavity induced a systemic antitumor response that would inhibit growth of a second wild-type (TK⁻) tumor implanted in the live. DHDK12 rat colon cancer cells were transduced in vitro with the retroviral HS-tk vector and established as a permanent cell line (TK⁺ cells). TK⁺ or TK⁻ DHDK12 cells (6×10⁶ cells) were injected intraperitoneally on day 0 into BD-IX rats. On day 10, TK⁻ cells (3×10⁶ cells) were injected into the liver in all the groups. The animals were then treated with GCV (150 mg/kg) for 13 days. TK⁺ peritoneal tumors underwent significant regression during therapy with GCV (0.05±0.004 g; n=7) compared to wild-type (TK⁻) tumors (2.2±0.7 g; n=6) (P<0.05). The volume to TK⁻ tumors in the liver was significantly lower in GCV-treated rats with TK⁺ peritoneal tumors (12.5±8.3 mm³) compared to rats with TK⁻ peritoneal tumors (96.7±18.1 mm³) (P<0.05). Histology of the liver tumors in the TK⁺ groups showed a dense monocytic infiltrate with fibrosis and only occasional viable tumor cells. Gene therapy with retroviral HS-tk vectors may provide a novel approach to treatment of gastrointestinal cancer by both direct cytotoxicity and an indirect mechanism that may included enhanced immunologic responses against disseminated disease. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, Calif., May 19–22, 1996.     

Potentiation of the antitumor effect of 11-keto-β-boswellic acid by its 3-α-hexanoyloxy derivative

We recently discovered that a propionyloxy derivative of 11-keto-β-boswellic acid (PKBA) showed better anticancer potential than other boswellic acids including AKBA, encompassing the importance of acyl group at the 3-α-hydroxy position of KBA. In continuation of our previous work, other higher derivatives (with increasing alkoxy chain length at 3-α-hydroxy position) including butyryloxy (BKBA) and hexanoyloxy (HKBA) derivatives of KBA were synthesized. The respective IC₅₀ values of BKBA and HKBA in HL-60 cells were found to be 7.7 and 4.5 μg/ml. IC₅₀ value of HKBA was comparatively lower than that of BKBA, and further lower than that of the previously reported derivative (PKBA, IC₅₀ 8.7 μg/ml). In order to compare the anticancer potential of HKBA with PKBA, detailed in vitro pro-apoptotic and in vivo anticancer studies were carried out. The induction of apoptosis by HKBA was measured using various parameters including fluorescence and scanning electron microscopy, DNA fragmentation and Annexin V-FITC binding. The extent of DNA damage was measured using neutral comet assay. HKBA was further evaluated for its effect on DNA cell cycle and mitochondria where it was found to arrest cells in G₂/M phase and also induced loss of mitochondrial membrane potential. These events were associated with increased expression of cytosolic cytochrome c and cleavage of PARP. Target based studies showed that HKBA inhibited the enzymatic activity of topoisomerases I and II at low doses than that of PKBA. In vivo studies also revealed a low dose inhibitory effect of HKBA on ascitic and solid murine tumor models.     

Nanostructured Lipid Carriers (NLC)-Based Gel for the Topical Delivery of Aceclofenac: Preparation, Characterization, and In Vivo Evaluation

The aim of this study was to prepare nanostructured lipid carriers (NLC)-based topical gel of aceclofenac for the treatment of inflammation and allied conditions. Stearic acid as the solid lipid, oleic acid as the liquid lipid, pluronic F68 as the surfactant, and phospholipon 90G as the co-surfactant were used. NLCs were prepared by melt-emulsification, low-temperature solidification, and high-speed homogenization methods. Characterization of the NLC dispersion was carried out through particle size analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and an in vitro release study. The anti-inflammatory effect of the NLC gel was assessed by the rat paw edema technique and compared to marketed aceclofenac gel. The NLC dispersions exhibited d_90% between 233 nm and 286 nm. All of the NLC showed high entrapment efficiency ranging from 67% to 82%. The particle size of NLC was further confirmed by the SEM study. The result of DSC showed that aceclofenac was dispersed in NLC in an amorphous state. Both the entrapment and release rate were affected by the percentage of oleic acid, but the method of preparation affected only the entrapment efficiency. The nanoparticulate dispersion was suitably gelled and assessed for in vitro permeation. Finally, NLC-based gels were found to possess superior (almost double) the anti-inflammatory activity compared to the marketed product. The anti-inflammatory activity of NLC gel showed a rapid onset of action, as well as a prolonged duration of action as compared with the marketed gel.     

Antitumor efficacy and apoptotic activity of substituted chloroalkyl 1H-benz[de]isoquinoline-1,3-diones: a new class of potential antineoplastic agents

A series of ten chloroalkyl 1H-benz[de]isoquinoline-1,3-diones (naphthalimides) were synthesized and evaluated for antitumor activity. Amongst them, new compounds 2d and 2i carrying a 6-NO₂ substituent in the aromatic portion of the molecule possessed significant antineoplastic activity. The most active compound 2i had elicited significant cytotoxicity in 15 human tumor cell lines namely Leukemia: MOLT-4, HL-60; Lymphoma: U-937; Colon: 502713, HT-29, SW-620, HCT-15, COLO-205; Liver: Hep-2; Prostate DU-145, PC-3; Breast: MCF-7; Neuroblastoma: IMR-32, SK-N-SH and Ovary: OVCAR-5 out of the 17 cell lines screened. Flow cytometric analysis performed to study the effect of compound 2i on the progression of cell cycle of MOLT-4 cells, revealed rise in sub-G₁ fraction and concomitant accumulation of cells in S and G₂/M phases, indicating apoptosis, mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. It also induced caspase-mediated apoptosis of MOLT-4 cells in a dose dependant manner. Light and electron microscopic studies revealed characteristic morphology of apoptotic MOLT-4 cells after in vitro treatment with 10 μM concentration of the compound. Apoptosis induction was also observed in HL-60 cells by compounds 2d and 2i to an extent much greater than camptothecin and cis-platin at 10 μM concentration. Both the compounds have shown minimal suppressive effect on human PBMC having high IC₅₀ values of 3,582 and 1,536 μM respectively. These compounds inhibited DNA and RNA synthesis in murine ascites Sarcoma-180 tumor cells in vitro at 8 μM concentration. Above results indicate promising chemotherapeutic potential of the key compound 2i.     

Inhibition of expression of anti-apoptotic protein Bcl-2 and induction of cell death in radioresistant human prostate adenocarcinoma cell line (PC-3) by methyl jasmonate

Hormone refractory human prostate cancer cell lines are known to be radioresistant, a feature attributed to their ability to induce anti-apoptotic proteins of the Bcl-2 family when exposed to radiation. We investigated whether pro-apoptotic compounds such as methyl jasmonate, a plant stress hormone, can counteract the radiation-induced anti-apoptotic mechanism in a human prostate cancer cell line PC-3. Significant (p < 0.05) increase in cytotoxicity was observed in the combined treatment groups compared to single treatments with methyl jasmonate or γ-radiation. Treatment of irradiated PC-3 cells with methyl jasmonate resulted in suppression of anti-apoptotic Bcl-2 protein and elevation of caspase-3 activity. Our results showed increased apoptosis in the combined treatment group as compared to the irradiated group or the untreated control. In summary, methyl jasmonate suppressed the radiation-induced Bcl-2 expression and enhanced the radiation sensitivity of human prostate cancer cells.     

An in vitro investigation to compare the surface roughness of auto glazed, reglazed and chair side polished surfaces of Ivoclar and Vita feldspathic porcelain

The change in surface roughness after different surface finishing techniques has attracted the attention of several prosthodontists regarding wear of opposing teeth or restorative material and the strength; plaque retention and appearance of the restoration. However, there is considerable controversy concerning the best methods to achieve the smoothest and strongest porcelain restorations after chair side clinical adjustments. The purpose of this in vitro study was to compare the average surface roughness of a self-glazed surface, a chair side polished surface and a reglazed surface of ceramic. Two feldspathic porcelain, namely VITA VMK94 (Vita Zahnfabrik, Bad Sachingen, Germany) and IVOCLAR CLASSIC (Vivadent AG, FL-9494 Schaan, Liechtenstein) were selected to fabricate 20 specimens of each in the shape of shade guide tabs. A medium-grit diamond rotary cutting instrument was used to remove the glaze layer, and then the surface of half the specimens were re-glazed and the other half were polished using a well-defined sequence of polishing comprising of: Shofu porcelain polishing system, White gloss disc/polishing wheel, Silicone cone with diamond polishing paste and finally with small buff wheel with pumice slurry. The surface roughness (Ra) (μm) of the specimens was evaluated using a profilometer and scanning electron microscope. The data were statistically analyzed by using Student’s t test. The results had shown that there is no statistically significant difference both quantitatively and qualitatively, between the surface roughness of reglazed and chair-side polished surface. In addition, both reglazed and chair-side polished surfaces are better than the autoglazed surface. Within all the groups, there is no significant difference between companies. Polishing an adjusted porcelain surface with the suggested sequence of polishing will lead to a finish similar to a re-glazed surface. Therefore chair-side polishing can be a good alternative to reglazing for finishing adjusted porcelain surface.     

Psychopharmacology of tic disorders in children and adolescents

Tics in children and adolescents are a common occurrence; however, a small proportion of these disorders require pharmacologic interventions. Several limitations exist with the use of pharmacologic interventions, and hence, a more ideal multidisciplinary approach is recommenced, with emphasis on nonpharmacologic management for improved functioning, adaptation, and comorbidities. Mutual and realistic goals ensure a trustful and successful relationship between the clinician and patient. An individualized plan is recommended with the goal of limiting side effects and managing comorbid conditions as a priority before addressing the tics specifically. This article reviews medications used to treat tic disorders in children and adolescents.