Antihyperglycemic, antihyperlipidemic and antioxidative evaluation of compounds from Senna sophera (L.) Roxb in streptozotocin-induced diabetic rats.

Senna sophera (L.) Roxb (Common name: Kasunda, Baner) (Leguminosae) is used as traditional medicine in Africa and Asia. The compounds were isolated from methanolic extract of leaves of Senna sophera (MFCS). Compound A was identified as Hexahydroxy diphenic acid and Compound B as Kaempferol. MFCS administration to diabetic rats exhibited significant reduction in the blood sugar level and showed gain in body weight. After the treatment of 100 mg/kg of MFCS, the blood sugar level was reduced to 52.33 ± 2.83 mg/dl in comparison to the blood sugar level of vehicle control 76.66 ± 3.17 mg/dl, whereas treatment with 50 mg/kg of MFCS reduced the blood sugar level slightly (72.33 ± 2.42 mg/dl). The daily continuous administration of MFCS for a period of 21 days normalised the serum lipid levels confirming the effect of MFCS on diabetic hyperlipidemia. Treatment with MFCS also reversed the activities of antioxidants, which could be a result of decreased lipid peroxidation.

Characteristics, detection methods and treatment of questionable occlusal carious lesions: findings from the national dental practice-based research network.

Questionable occlusal carious lesions (QOC) can be defined as an occlusal tooth surface with no cavitation and no radiographic radiolucencies, but caries is suspected due to roughness, surface opacities or staining. An earlier analysis of data from this study indicates 1/3 of patients have a QOC. The objective of this report has been to quantify the characteristics of these common lesions, the diagnostic aids used and the treatment of QOC. A total of 82 dentist and hygienist practitioner-investigators from the USA and Denmark in the National Dental Practice-Based Research Network participated. When consenting patients presented with a QOC, information was recorded about the patient, tooth, lesion and treatments. A total of 2,603 QOC from 1,732 patients were analyzed. The lesions were usually associated with a fissure, on molars, and varied from yellow to black in color. Half presented with a chalky luster and had a rough surface when examined with an explorer. There was an association between color and luster: 10% were chalky-light, 47% were shiny-dark and 42% were mixtures. A higher proportion of chalky than of shiny lesions were light (22 vs. 9%; p < 0.001). Lesions light in color were less common in adults than in pediatric patients (9 vs. 32%; p < 0.001). Lesions that were chalky and light were more common among pediatric than among adult patients (22 vs. 6%; p < 0.001). This is the first study to investigate characteristics of QOC in routine clinical practice. Clinicians commonly face this diagnostic uncertainty. Determining the characteristics of these lesions is relevant when making diagnostic and treatment decisions.

Carbapenem resistance and phenotypic detection of carbapenemases in clinical isolates of Acinetobacter baumannii.

BACKGROUND AND OBJECTIVES: Multidrug-resistant Acinetobacter baumannii (MDR-Ab) reported worldwide has become one of the most difficult nosocomially acquired Gram-negative pathogens to control and treat. The clinical utility of carbapenems is under threat with the emergence of acquired carbapenemases, particularly Ambler class B metallo-lactamases (MBL). Because of the global increase in the occurrence and dissemination of MBLs, early detection is critical. This study was undertaken to detect resistance to carbapenems in clinical isolates of A. baumannii from hospitalized patients by both disk-diffusion and minimum inhibitory concentration (MIC) methods and to assess the rate of carbapenemase and MBL production among the isolates. MATERIALS AND METHODS: A. baumannii were identified from various clinical samples and antibiotic susceptibility profile was determined by the standard disk-diffusion method. Meropenem-resistant strains were tested further by agar dilution MIC for meropenem. Resistant isolates were screened for carbapenemase production by the modified Hodge test and positive isolates were further checked for metallo-ß-lacatmase production by the EDTA disk synergy test. RESULTS: 42 isolates (31.81%) showed resistance to meropenem by the disk diffusion method. 47.6% were carbapenemase positive by the modified Hodge test and 19% were MBL producers phenotypically by the EDTA disc synergy test (EDS). These meropenem-resistant isolates were resistant to most of the other antibiotics tested. These 42 isolates were recovered mostly from patients admitted to intensive care units. Four isolates of the A. baumannii complex were pan drug resistant and showed resistance to even tigecycline and polymyxin B. CONCLUSION: Carbapenem resistance has been increasingly reported, necessitating their detection. This study reports simple, carbapenemase, and MBL detection method that can be easily incorporated into the daily routine of a clinical laboratory.

Refractory Crohn's disease of the vulva treated with infliximab: a case report.

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disorder of the gastrointestinal tract. The common presentation includes abdominal pain, abdominal cramping and diarrhea. Many patients may exhibit systemic symptoms of fever and weight loss. Approximately 20% to 40% of patients will experience extraintestinal manifestations that involve the eyes, skin and joints. Women may experience a variety of gynecological manifestations, including vulvovaginal involvement, which is often not recognized and also difficult to treat. A case of refractory vulvovaginal CD is presented and the literature of gynecological manifestations of CD and its treatment are reviewed.

Evaluation of tumor-specific promoter activities in melanoma.

Gene therapy is a novel therapy for melanoma. To date, however, there is still no powerful tumor specific promoter (TSP) to restrict the transgene expression in melanoma cells. In order to define a useful TSP for targeting in the context of melanoma gene therapy, four promoters, the cyclooxygenase-2 (Cox-2), alpha-chemokine SDF-1 receptor (CXCR4), epithelial glycoprotein 2 (EGP-2), and survivin, were tested in both established melanoma cell lines and primary melanoma cells. We employed recombinant adenoviral vectors (reAds) each with a candidate TSP (the Cox-2, CXCR4, EGP-2, or survivin), a reporter luciferase gene, and a poly-A signal, all of which were inserted into the E1-deleted region. A reAdGL3Bcytomegalovirus (CMV), containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity. Luciferase activity was measured in multiple tumor cell lines and two primary melanoma cell cultures after infection with reAds. Human epithelial melanocytes, HEM, were used as normal control. In contrast to three other promoters, the survivin promoter exhibited the highest activities within both melanoma cell lines and primary melanoma cells, but not in HEMs. Additionally, the survivin promoter exhibited very low activities in major mouse organs including the liver, in vivo. EGP-2 is not active in melanoma; messenger RNA expressions were correlated to promoter activities both in melanoma cell lines and primary cell cultures. Thus, these data suggest that the survivin promoter achieved a 'tumor-on/liver-off' profile, and thus represents a potentially useful tumor-specific promoter with applications for transcriptional targeting of Ad vector-based cancer gene therapy or oncolysis to melanoma.

Comparative analysis of the antibacterial effects of combined mouthrinses on Streptococcus mutans.

BACKGROUND/AIMS: Chlorhexidine has been proposed as a potent chemotherapeutic agent against oral bacteria. However, there are some inconsistent results regarding the usefulness of chlorhexidine mouthrinse as an antimicrobial for Streptococcus mutans. The purpose of this study was to investigate the effectiveness of combining oral rinses to reduce S. mutans levels in human saliva. METHODS: Sixteen healthy adult subjects were randomly assigned to one of four rinse groups using a 4-cell crossover design. The groups rinsed twice a day for 7 days with one of the following: 0.12% chlorhexidine (PerioGard), 1.5% hydrogen peroxide (Peroxyl), a combined chlorhexidine+hydrogen peroxide, or water (control). Every 5 weeks, each group initiated a different rinse. Saline wash samples were collected on days 7 and 21 for assessment of S. mutans and total streptococci. RESULTS: No significant differences were seen in S. mutans levels among the groups; however, the levels of total streptococci on day 7 samples were significantly lower in the chlorhexidine and chlorhexidine+hydrogen peroxide groups than in the hydrogen peroxide and control groups. There was no additional decrease seen in S. mutans or total streptococci levels in the group receiving chlorhexidine+hydrogen peroxide compared to chlorhexidine alone. CONCLUSIONS: Sample variation was high throughout the study, with a significant trend toward lower counts as the study progressed. Adding hydrogen peroxide to the chlorhexidine mouthrinse did not result in a further decrease in S. mutans levels.

Octreotide in intestinal lymphangiectasia: lack of a clinical response and failure to alter lymphatic function in a guinea pig model.

Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. Octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing lymphatic pumping.

Transcriptional targeting of adenoviral vector through the CXCR4 tumor-specific promoter.

Adenoviral vectors are considered to be good gene delivery vectors for cancer gene therapy due to their wide host tissue range and cell cycle-independent infectivity. However, the disadvantages include the lack of specificity for cancer cells and the high liver accumulation in vivo. The human CXCR4 gene is expressed at high levels in many types of cancers, but is repressed in the liver. We explored the CXCR4 promoter as a candidate to restrict adenoviral transgene expression to tumor cells with a low expression in host tissues. The luciferase activities in multiple cancer cell lines infected with recombinant adenovirus reAdGL3BCXCR4 or the control vector reAdGL3BCMV revealed that the CXCR4 promoter exhibited relatively high transcriptional activity in a breast cancer cell line, MDA-MB-361, and two ovarian cancer cell lines, OVCAR-3 and SKOV3. ip1, 65% (P=0.0087), 16.7% (P=0.1) and 20% (P=0.0079) compared to that of the CMV promoter, respectively, and low expression, 4.9 and 0.1%, respectively, in both normal cell lines HFBC and HMEC. In addition, CXCR4 had a low expression of luciferase (0.32%) compared to that of the CMV promoter in mouse liver in vivo. The data also revealed that the CXCR4 promoter was a stronger tumor-specific promoter (TSP) than the Cox-2M promoter in primary melanomas obtained from two patients. The CXCR4 promoter is shown to have a 'tumor-on' and 'liver-off' status in vitro and in vivo, and CXCR4 may prove to be a good candidate TSP for cancer gene therapy approaches for melanoma and breast cancers.

Identification of genetic alterations related to chemoresistance in epithelial ovarian cancer.

OBJECTIVE: After the completion of primary chemotherapy, the majority of advanced ovarian cancer patients have persistent, chemoresistant disease. Comparative genomic hybridization (CGH) has been used to study genetic alterations that may be responsible for chemoresistance in ovarian cancer. CGH is a useful, genomewide screen but resolution is limited to 5-10 Mb. Recently, quantitative microsatellite analysis (QuMA), a TaqMan-based quantitative PCR technology, has been used for higher resolution of DNA copy number abnormalities. Our goal is to identify specific chromosomal aberrations correlated with platinum resistance. METHODS: Snap-frozen ovarian tissue samples taken from 22 patients with ovarian cancer between 1994 and 1998 were analyzed. Patients whose ovarian cancer actually demonstrated growth during platinum-combination treatment or no objective evidence of regression following four to six cycles of therapy were considered to have clinically defined platinum-resistant disease. QuMA was carried out at the following loci using the ABI Prism 7700 (TaqMan) instrument with a microsatellite repeat probe: D3S1553, D3S1617, D5S464, D5S630, D6S1581, D6S446, D8S557, D19S208, D20S196, DXS1068. Fisher's exact test, exact logistic regression, and the Cochran-Armitage trend test were used. Because of multiple hypothesis testing, the P values were adjusted with the Bonferroni procedure to limit the familywise error rate to at most 5%. RESULTS: Of the 22 patients, 12 (54.5%) were platinum-sensitive and 10 (45.5%) were platinum-resistant. When comparing sensitive and resistant patients, no statistically significant difference was noted among stage, grade, histology, and age (P = 0.1292, P = 1.0000, P = 1.0000, P = 1.0000, respectively). In the QuMA analysis, 10 of the 14 (71.4%) patients who had a low copy number of D6S1581 were platinum-resistant, while none of the patients with a normal or high copy number of D6S1581 were platinum-resistant. This was statistically significant when the marker data were treated as either a continuous or a categorical variable (P = 0.0410 and P = 0.0170, respectively). No other loci correlated significantly with platinum resistance. CONCLUSIONS: D6S1581 was the only genetic marker, of those examined, significantly related to chemoresistance. Patients with a loss of D6S1581 are more likely to be platinum-resistant. Identification of genetic alterations associated with platinum resistance detected by QuMA may contribute to a better understanding of clinical behavior and chemotherapy treatment options for patients.

Positron emission tomography/computed tomography imaging for the detection of recurrent ovarian and fallopian tube carcinoma: a retrospective review.

PURPOSE: Imaging modalities to evaluate ovarian/fallopian tube cancer patients for recurrence are limited. Positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound lack the sensitivity to consistently detect recurrence or measurable disease in these patients. A new technique combines PET and CT (PET/CT) images to identify increased metabolic activity and to locate that signal with improved anatomic specificity. The objective of this study is to compare PET/CT, CT, and histologic findings in patients with recurrent ovarian/fallopian tube cancers. METHODS: Retrospective chart review of eight patients with primary ovarian (n = 6) or fallopian tube (n = 2) cancer was performed. All eight patients underwent initial cytoreductive surgery. Five patients initially received chemotherapy, one received radioactive phosphorus ((32)P), one received tamoxifen, and one received no therapy. Seven of eight patients had a suspected recurrence based on clinical examination, elevated CA-125 level, and/or abnormal CT findings; one patient requested a PET/CT. Histologic findings from surgery were correlated with PET/CT and CT findings. RESULTS: All eight patients had positive histology, and of these, seven patients had a negative CT and five patients had lesions that were correctly identified by PET/CT. CONCLUSIONS: Five of the eight (62%) patients had recurrent disease based on correlative histology with a positive PET/CT and a negative CT. These preliminary findings suggest that combined PET/CT may be an effective means of identifying patients with recurrent ovarian/fallopian tube cancer. Such patients could potentially proceed to salvage treatment and avoid the morbidity and expense of surgical assessment. Pilot studies comparing CT, PET, PET/CT, and histologic findings are underway.

Ectomycorrhizal fungal associates of Pinus contorta in soils associated with a hot spring in Norris Geyser Basin, Yellowstone National Park, Wyoming.

Molecular methods and comparisons of fruiting patterns (i.e., presence or absence of fungal fruiting bodies in different soil types) were used to determine ectomycorrhizal (EM) associates of Pinus contorta in soils associated with a thermal soil classified as ultra-acidic to extremely acidic (pH 2 to 4). EM were sampled by obtaining 36 soil cores from six paired plots (three cores each) of both thermal soils and forest soils directly adjacent to the thermal area. Fruiting bodies (mushrooms) were collected for molecular identification and to compare fruiting body (above-ground) diversity to below-ground diversity. Our results indicate (i) that there were significant decreases in both the level of EM infection (130 +/- 22 EM root tips/core in forest soil; 68 +/- 22 EM root tips/core in thermal soil) and EM fungal species richness (4.0 +/- 0.5 species/core in forest soil; 1.2 +/- 0.2 species/core in thermal soil) in soils associated with the thermal feature; (ii) that the EM mycota of thermal soils was comprised of a small set of dominant species and included very few rare species, while the EM mycota of forest soils contained a few dominant species and several rare EM fungal species; (iii) that Dermocybe phoenecius and a species of Inocybe, which was rare in forest soils, were the dominant EM fungal species in thermal soils; (iv) that other than the single Inocybe species, there was no overlap in the EM fungal communities of the forest and thermal soils; and (v) that the fungal species forming the majority of the above-ground fruiting structures in thermal soils (Pisolithus tinctorius, which is commonly used in remediation of acid soils) was not detected on a single EM root tip in either type of soil. Thus, P. tinctorius may have a different role in these thermal soils. Our results suggest that this species may not perform well in remediation of all acid soils and that factors such as pH, soil temperature, and soil chemistry may interact to influence EM fungal community structure. In addition, we identified at least one new species with potential for use in remediation of hot acidic soil.

Stability indicating HPTLC method for the simultaneous determination of pseudoephedrine and cetirizine in pharmaceutical formulations.

The combination of pseudoephedrine and cetirizine is widely used in the treatment of allergic rhinitis. A rapid, selective and stability indicating high performance thin layer chromatographic method was developed and validated for their simultaneous estimation in pharmaceutical dosage forms. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of ethyl acetate-methanol-ammonia (7:1.5:1, v/v/v). This system was found to give compact spots for both pseudoephedrine (Rf value of 0.69+/-0.01) and cetirizine (Rf value of 0.38+/-0.01). Also the degraded products were well separated from the pure drugs. Spectrodensitometric scanning-integration was performed at a wavelength of 240 nm. The polynomial regression data for the calibration plots showed good linear relationship with r(2)=0.9947 in the concentration range of 10-26 microg for pseudeophedrine and 200-1200 ng for cetirizine with r(2)=0.9973. The method was validated for precision, accuracy, ruggedness and recovery. The minimum detectable amounts were found to be 2 microg and 500 pg for pseudoephedrine and cetirizine, respectively. The limits of quantitation were found to be 6 microg for pseudoephedrine and 800 pg for cetirizine. Both the drugs do not undergo degradation under acidic and basic conditions. The samples degraded with hydrogen peroxide showed additional peaks at Rf values of 0.75 and 0.28 for pseudoephedrine and cetirizine, respectively. This indicates that both the drugs are susceptible to oxidation. Statistical analysis proves that the method is reproducible and selective for the simultaneous estimation of pseudoephedrine and cetirizine. As the method could effectively separate the drugs from their degradation products, it can be employed as a stability indicating one.

Complications associated with intraperitoneal chemotherapy catheters.

PURPOSE: The goal of this work was to determine the complication rate and any predisposing risk factors associated with subcutaneous intraperitoneal (ip) catheters used in the treatment of patients with advanced ovarian cancer. METHODS: We retrospectively reviewed the charts of 301 patients who had a subcutaneous Bardport catheter placed for administration of ip chemotherapy at Memorial Sloan--Kettering Cancer Center (MSKCC) from December 1989 to May 1997. RESULTS: Thirty (10%) patients were identified as having catheter-related complications, with 19 (6.3%) experiencing inflow obstruction and 11 (3.6%) experiencing infection. Only 21 of 301 (7%) required cessation of chemotherapy prior to its expected completion, with 14 (4.6%) occurring in the malfunction group and 7 (2.3%) in the infection group. Three hundred thirteen patients received an ip catheter; however, 12 patients who received their ip chemotherapy elsewhere were excluded when determining the complication rate. Overall, 218 of 313 (69.6%) catheters were placed at the time of laparotomy, 61 of 313 (19.5%) catheters were placed at the time of laparoscopy, and 34 of 313 (10.9%) were placed as a separate procedure. In the malfunction group, 18 of 19 (94.7%) patients had their catheters placed at the time of laparotomy, none were placed at the time of laparoscopy, and 1 of 19 (5.3%) was placed as a separate procedure. In the infection group, 8 of 11 (72.7%) catheters were placed at laparotomy, 2 of 11 (18.3%) were placed at the time of laparoscopy, and 1 of 11 (9.0%) was placed as a separate procedure. Complications occurred in 3 of 54 (5.5%) patients who received platinum alone, 11 of 134 (8.2%) who received platinum in combination, 2 of 43 (4.7%) who received paclitaxel alone, 13 of 61 (21.3%) who received mitoxantrone alone or in combination, and 1 of 9 (11.1%) who received other regimens. CONCLUSION: Subcutaneous ip catheters are associated with a lower rate of catheter-related complications than previously reported, perhaps due in part to both avoiding insertion of ip catheters at the time of bowel surgery and placing ip catheters at the time of laparoscopy.

Intraperitoneal cisplatin and intravenous paclitaxel in the treatment of epithelial ovarian cancer patients with a positive second look.

OBJECTIVE: The aim of this study was to review the role and safety of intraperitoneal (IP) cisplatin and intravenous (IV) paclitaxel in platinum-sensitive epithelial ovarian cancer patients who were found to have small-volume disease (<1 cm) at the time of their second-look procedure. METHODS: In a retrospective review, 32 patients with small-volume disease had an IP Bardport catheter placed at the time of second look at Memorial Sloan-Kettering Cancer Center (1995-1998). Patients received IP cisplatin (75 mg/m(2)) every 3 weeks and either IV paclitaxel (135 mg/ m(2)) every 3 weeks or IV paclitaxel (80 mg/m(2)) weekly for a maximum of five cycles. RESULTS: Twenty-four (75%) of 32 patients received IP cisplatin/IV paclitaxel every 3 weeks and 8 (25%) received IP cisplatin every 3 weeks with weekly IV paclitaxel. Seven (21.9%) of 32 patients required interruption of treatment secondary to neuropathy. Of these, 4 (15.6%) were changed to another IV chemotherapeutic agent, and 3 (9.3%) required discontinuation of IV paclitaxel only. Two (6%) patients required IP port removal secondary to malfunction and were changed to IV therapy and 1 (3%) requested discontinuation of IP therapy secondary to abdominal pain. Median follow-up was 19 months (mean, 20.1 months; range, 6-36 months). Progression of disease after completion of IP therapy was documented by clinical exam, abnormal CT, and/or rising CA-125 levels. The median progression-free interval was 13 months (mean, 15.1 months; range, 2-33 months). Median overall survival was 27 months (mean, 34.2 months; range, 10-42 months). At the time of review, 13 (40.6%) of the 32 patients were alive with disease, 7 (21.9%) were without evidence of disease, and 12 (37.5%) were dead of disease. CONCLUSION: IP cisplatin in combination with IV paclitaxel appears to be no more effective than other reported regimens as second-line therapy for patients with persistent small-volume disease. Neurotoxicity is dose limiting, and the combination cannot be recommended for the routine care of persistent peritoneal cancers.

Taxol-induced bcl-2 phosphorylation in ovarian cancer cell monolayer and spheroids.

Expression of Bcl-2, Bax, p53 and induction of apoptosis were studied in cisplatin or Taxol treated monolayer and spheroid cultures of ovarian cancer cell lines (SKOV-3, UL-1, UL-3C). While cisplatin (15-75 microg/ml) induced apoptosis in monolayer and spheroid cultures, Taxol (100-800 nM) induced fragmentation in monolayers only. Cisplatin induced up to 5-fold DNA fragmentation in monolayers, while 3-fold (UL-3C, SKOV-3), and 1.5-fold (UL-1) in spheroids. Taxol treatment of monolayers resulted in the characteristic phosphorylation of Bcl-2, which was not demonstrated in spheroid cultures. Bax expression was reduced in spheroids following cisplatin or Taxol treatment, while p53 levels remained unchanged.

Intraperitoneal chemotherapy strategies in the treatment of epithelial ovarian carcinoma.

The intraperitoneal delivery of chemotherapeutic agents is presently being investigated as a part of salvage treatment for epithelial ovarian cancer. There are several promising new agents that appear to demonstrate a benefit in selected patients.

Study of suspected plague cases for isolation and identification of Yersinia pestis.

A total of 62 suspected patients of plague were investigated for evidence of Yersinia pestis, by blood culture, lymph node aspirate culture, sputum culture, animal inoculation and serology for f1 antibodies against f1 antigen of Yersinia pestis. None of the samples was positive by direct smear examination and culture for Yersinia pestis, as well as for serology. The non positivity of the cultures is discussed.