A case of multiple squamous cell carcinomas arising from red tattoo pigment.

Ornamental tattooing involves the administration of exogenous pigments into the skin to create a permanent design. Our case focuses on a 62-year-old woman who presented with an inflamed enlarging nodule on her right proximal calf, which arose within the red pigment of an ornamental tattoo. The nodule was diagnosed as squamous cell carcinoma (SCC) and subsequently excised. Over the course of the following year, the patient was diagnosed with a total of five additional SCCs that also arose within the red pigment of the tattoo. The increased popularity of tattooing and the lack of industry safety standards for tattoo ink production, especially metal-laden red pigments, may lead to more cases of skin cancer arising within tattoos among patients of all ages.

Use of light emitting diodes (LEDs) for enhanced lipid production in micro-algae based biofuels.

Microalgae are an alternative source for renewable energy to overcome the energy crises caused by exhaustion of fuel reserves. Algal biofuel technology demands a cost effective strategy for net profitable productivity. Inconsistent illumination intensities hinder microalgal growth. The light-utilizing efficiency of the cells is critical. Light scarcity leads to low production and high intensities cause photo-inhibition. We report effective usage of LEDs of different band wavelengths on the growth of microalgae in a closed, controlled environment to generate biomass and lipid yields. Among the different intensity and wavelengths tested. The light intensities of 500lx of blue-red combination gave maximum biomass in terms of cell density. LED of red light 220lx wavelength doubled the lipid dry weight from 30% (w/w) in white light to 60% (w/w). Thin layer lipid chromatogram demonstrated a dense and prominent spot of triacylglycerols in the red light, 220lx grown cultures. The FTIR profile indicates that different wavelength exposure did not alter the functional groups or change the chemical composition of the extracted lipids ensuring the quality of the product. We reiterate the fact that combination of red and blue LEDs is favoured over white light illumination for generation of biomass. In addition, we report an exciting finding of exposure to LEDs of red wavelength post-biomass generation lead to enhanced lipid production. This simple process doubled the lipid content harvested in 20days culture period.

Synergistic metabolic benefits of an exenatide analogue and cholecystokinin in diet-induced obese and leptin-deficient rodents.

AIM: To test the impact of cholecystokinin (CCK) plus either amylin or a glucagon-like peptide-1 receptor (GLP-1R) agonist on metabolic variables in diet-induced obese (DIO) rodents. METHODS: A stabilized acetylated version of CCK-8 (Ac-Y*-CCK-8), selective CCK1 receptor (CCK1R) or CCK2 receptor (CCK2R) agonists, amylin or the GLP-1R agonist and exenatide analogue AC3174 were administered in select combinations via continuous subcutaneous infusion to DIO rats for 14 days, or Lep(ob) /Lep(ob) mice for 28 days, and metabolic variables were assessed. RESULTS: Combined administration of Ac-Y*-CCK-8 with either amylin or AC3174 induced greater than additive weight loss in DIO rats, with the overall magnitude of effect being greater with AC3174 + Ac-Y*-CCK-8 treatment. Co-infusion of AC3174 with a specific CCK1R agonist, but not a CCK2R agonist, recapitulated the weight loss mediated by AC3174 + Ac-Y*-CCK-8 in DIO rats, suggesting that synergy is mediated by CCK1R activation. In a 4 × 4 full-factorial response surface methodology study in DIO rats, a synergistic interaction between AC3174 and the CCK1R-selective agonist on body weight and food intake was noted. Co-administration of AC3174 and the CCK1R-selective agonist to obese diabetic Lep(ob) /Lep(ob) mice elicited a significantly greater reduction in percentage of glycated haemoglobin and food intake relative to the sum effects of monotherapy groups. CONCLUSIONS: The anti-obesity and antidiabetic potential of combined GLP-1R and CCK1R agonism is an approach that warrants further investigation.

Effectiveness of 'in-cast' pneumatic intermittent pedal compression for the pre-operative management of closed ankle fractures: a clinical audit.

BACKGROUND: Timing of surgery for ankle fractures is largely dependent on the condition of the surrounding soft-tissues. This study aimed to determine the clinical effectiveness of a pre-operative in-cast artero-venous (AV) impulse device in the management of closed ankle fractures requiring surgery. METHODS: A consecutive series of 64 closed ankle fractures were managed using the AV impulse system prior to surgery. Patients were compared to 73 consecutive closed ankle fractures managed surgically in the same unit immediately prior to the implementation of the AV impulse device study. Outcomes measured were time to surgery, length of hospital stay and surgical site infections. RESULTS: Median length of time to surgery, hospital stay duration and surgical site infections were all significantly reduced in the study group as compared to the control group. CONCLUSIONS: In-cast intermittent AV compression foot pumps in the pre-operative management of closed ankle fractures were associated with earlier surgery, earlier discharge and reduced complications.

Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice.

The combined glucose-lowering effect of exenatide and dapagliflozin has not yet been studied. We investigated this combination (single-dose or 4-week dosing) in diabetic ob/ob mice. Vehicle-corrected basal glucose showed greater reduction 1 h following exenatide + dapagliflozin than with exenatide or dapagliflozin alone, and stayed significantly lower for all groups versus vehicle over 3 h. During an oral glucose tolerance test, glucose excursion (30 min post-dose) was significantly lower for exenatide + dapagliflozin versus exenatide or dapagliflozin, or vehicle. Exenatide + dapagliflozin and exenatide, but not dapagliflozin alone, reduced glucose excretion over 24 h versus vehicle. After dosing for 4 weeks, exenatide, dapagliflozin and exenatide + dapagliflozin similarly decreased haemoglobin A1c (HbA1c). Body weight was reduced only with exenatide or exenatide + dapagliflozin. The glomerular filtration rate was similar with exenatide, dapagliflozin and vehicle, and increased with exenatide + dapagliflozin. Optimized combinatorial dosing of these antidiabetic agents may provide additive glucose lowering in type 2 diabetes mellitus.

A novel long-acting glucose-dependent insulinotropic peptide analogue: enhanced efficacy in normal and diabetic rodents.

AIM: Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone that is released from intestinal K cells in response to nutrient ingestion. We aimed to investigate the therapeutic potential of the novel N- and C-terminally modified GIP analogue AC163794. METHODS: AC163794 was synthesized by solid-phase peptide synthesis. Design involved the substitution of the C-terminus tail region of the dipeptidyl peptidase IV (DPP-IV)-resistant GIP analogue [d-Ala(2) ]GIP(1-42) with the unique nine amino acid tail region of exenatide. The functional activity and binding of AC163794 to the GIP receptor were evaluated in RIN-m5F ß-cells. In vitro metabolic stability was tested in human plasma and kidney membrane preparations. Acute insulinotropic effects were investigated in isolated mouse islets and during an intravenous glucose tolerance test in normal and diabetic Zucker fatty diabetic (ZDF) rats. The biological actions of AC163794 were comprehensively assessed in normal, ob/ob and high-fat-fed streptozotocin (STZ)-induced diabetic mice. Acute glucoregulatory effects of AC163794 were tested in diet-induced obese mice treated subchronically with AC3174, the exendatide analogue [Leu(14) ] exenatide. Human GIP or [d-Ala(2) ]GIP(1-42) were used for comparison. RESULTS: AC163794 exhibited nanomolar functional GIP receptor potency in vitro similar to GIP and [d-Ala(2) ]GIP(1-42). AC163794 was metabolically more stable in vitro and displayed longer duration of insulinotropic action in vivo versus GIP and [d-Ala(2) ]GIP(1-42). In diabetic mice, AC163794 improved HbA1c through enhanced insulinotropic action, partial restoration of pancreatic insulin content and improved insulin sensitivity with no adverse effects on fat storage and metabolism. AC163794 provided additional baseline glucose-lowering when injected to mice treated with AC3174. CONCLUSIONS: These studies support the potential use of a novel GIP analogue AC163794 for the treatment of type 2 diabetes.

Interactions of amylinergic and melanocortinergic systems in the control of food intake and body weight in rodents.

AIMS: Amylinergic and melanocortinergic systems have each been implicated in energy balance regulation. We examined the interactive effects of both systems using gene knockout and pharmacological approaches. METHODS: Acute food consumption was measured in overnight fasted male wild-type (WT) and melanocortin-4 receptor (MC-4R) deficient rats and in male and female WT and amylin knockout mice (AmyKO). Changes in food intake, body weight and composition in male WT and MC-4R deficient rats and in male diet-induced obese (DIO) rats. Pharmacological treatments included either rat amylin, murine leptin and/or the MC-4R agonist, Ac-R[CEH-dF-RWC]-amide. RESULTS: Amylin (10 µg/kg, IP) decreased food intake in WT but not in MC-4R deficient rats (30 and 60 min post-injection). Ac-R[CEH-dF-RWC]-amide (100 µg/kg, IP) suppressed food intake similarly in male WT and AmyKO, but was ineffective in female AmyKO. Amylin (50 µg/kg/day for 28 days) and leptin (125 µg/kg/day) synergistically reduced food intake and body weight in WT and MC-4R deficient rats to a similar extent. Amylin (100 µg/kg) combined with Ac-R[CEH-dF-RWC]-amide (100 µg/kg, IP) decreased acute food intake over 3 h to a greater extent than either agent alone in fasted mice. In DIO rats, additive anorexigenic, weight- and fat-lowering effects were observed over 12 days with the combination of rat amylin (50 µg/kg/day) and Ac-R[CEH-dF-RWC]-amide (2.3 mg/kg, SC injected daily). CONCLUSIONS: Although amylin's acute anorexigenic effects are somewhat blunted in MC-4R deficiency and those of MC-4R agonism in amylin deficiency, these effects are surmountable with pharmacological administration lending therapeutic potential to combined amylin/melanocortin agonism for obesity.

Isolation and Characterization of Antibacterial Compound from a Mangrove-Endophytic Fungus, Penicillium chrysogenum MTCC 5108.

Microorganisms, especially endophytic fungi that reside in the tissue of living mangrove plants, seem to play a major role in meeting the general demand for new biologically active substances. During the course of screening for biologically active secondary metabolites from marine microorganisms, an antibiotic compound containing an indole and a diketopiperazine moiety was isolated from the culture medium of Penicillium chrysogenum, (MTCC 5108), an endophytic fungus on the mangrove plant Porteresia coarctata (Roxb.). The cell free culture medium of P. chrysogenum showed significant activity against Vibrio cholerae, (MCM B-322), a pathogen causing cholera in humans. Bioassay guided chemical characterization of the crude extract led to the isolation of a secondary metabolite possessing a molecular formula C19H21O2N3. Its antibacterial activity was comparable with standard antibiotic, streptomycin. This compound (1) was found to be (3,1'-didehydro-3[2″(3'″,3'″-dimethyl-prop-2-enyl)-3″-indolylmethylene]-6-methyl pipera-zine-2,5-dione) on the basis of mass spectrometry, infrared spectroscopy and one and two-dimensional nuclear magnetic resonance analysis.

Antimicrobial activity of marine sponge Clathria indica (Dendy, 1889).

Sponges are sessile filter feeders that have developed efficient defense mechanisms against foreign invaders such as viruses, bacteria or eukaryotic organisms. Antimicrobial peptides are known as major components of the innate immune defense system in marine invertebrates. The aim of the present work was to study the antimicrobial properties of the Indian sponge Clathria indica with special reference to the identification of antimicrobial peptides. Crude methanolic extract and its chloroform, n-butanol and aqueous fractions were tested against 16 human pathogens which include eleven bacteria with four of them being multidrug resistant and five pathogenic fungi. All fractions showed effective antibacterial activity against common and multidrug-resistant Salmonella typhi and antifungal activity against C. albicans and C. neoformans. However, they were ineffective against Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes and Staphylococcus aureus. Chloroform fraction being the most potent among the fractions tested on chemical investigation was indicative of the presence of peptides as evidenced by ninhydrin positive spots on TLC and presence of peptide bonds by NMR. Its ESI-MS showed presence of several peptides in the range of m/z 850 to 980. Structure of three peptides has been tentatively assigned by ESI-MS/MS or tandem mass analysis, on the basis of the amino acid sequence established. The results clearly show that the sponge C. indica represent an interesting source of marine invertebrates-derived antimicrobial peptides in the development of new strategies to treat various infectious diseases.

Cystic fibrosis and survival to 40 years: a study of cystic fibrosis transmembrane conductance regulator function.

Significant survival heterogeneity exists in cystic fibrosis. Our aim was to determine whether residual function of the cystic fibrosis transmembrane conductance regulator (CFTR) is present in long-term survivors with severe mutations. Nasal potential difference (PD) and sweat chloride were measured in 34 long-term survivors (aged ≥ 40 yrs) and compared with young patients (18-23 yrs) with severe (n = 30) and mild (n = 31) lung disease. Baseline PD was not significantly different across the three groups (long-term survivors, -42.8 (range -71.0- -20.5) mV; young/mild, -40.5 (-58.8- -19.5) mV; young/severe,-46.3 (-74.0- -20.0) mV). Response to amiloride (ΔAmil) was significantly different across the three groups (p = 0.01); long-term survivors had values (27.8 (range 8.5-46) mV) which were not different to either young group, but the young/severe group had significantly higher values (29.5 (11-47) mV) than those in the young/mild group (22.0 (7-39) mV; p<0.01). Baseline PD and ΔAmil were associated with forced expiratory volume in 1 s (FEV1) (co-efficient (95% CI) -0.13 (-0.23- -0.03); p = 0.009 and -0.12 (-0.20- -0.04); p = 0.003, respectively). Sweat chloride was lowest (p <0.05) in the young/severe group (93.5 (74-111) mmol·L⁻¹ versus 98.8 (76.5-116.0) mmol·L⁻¹; long-term survivors; and 99.5 (80.0-113.5) mmol·L⁻¹; young/mild). Δ Amil is associated with FEV1 but our findings indicate that long-term survival cannot be explained by residual CFTR function when measurements are taken in later life.

A new xenicane norditerpene from the Indian marine gorgonian Acanthogorgia turgida.

Chemical investigation of the liposoluble extract of the gorgonian Acanthogorgia turgida, from Indian coasts, led us to isolate a new xenicane-based norditerpene, isoacalycixeniolide-A (1), along with the known structurally related compounds 2-6. The structure of the norditerpene (1) was elucidated by spectral methods (mainly by NMR techniques), whereas the absolute stereochemistry was suggested by the application of circular dicroism methodology.

Meaningful differences in maternal smoking behaviour during pregnancy: implications for infant behavioural vulnerability.

BACKGROUND: Smoking during pregnancy has been consistently associated with risk of problem behaviour in offspring. There is debate about whether this association reflects a teratological effect or is a marker for problematic maternal characteristics. We test these "competing" hypotheses by examining whether (1) exposure is associated with an early risk pathway by testing its association with infant temperamental difficultness, and (2) whether pregnancy quitting is associated with an early protective pathway, testing its association with easy infant temperament. METHODS: We used the 9-month-old sweep of the Millennium Cohort Study, a cohort of over 18,000 infants born in 2000-2. Mothers were classified as pregnancy non-smokers, quitters and light or heavy smokers. Temperamental positive mood, receptivity to novelty and regularity were assessed with the Carey Infant Temperament Scale. RESULTS: Pregnancy quitters had infants with the highest scores of easy temperament and heavy smokers had infants with the lowest scores (F = 28.51, p<0.001). Pregnancy smoking also predicted difficult temperament: heavy smoking was associated with increased risk of low positive mood (OR = 1.17, p = 0.09). In contrast, pregnancy quitting exerted a protective effect with decreased risk of distress to novelty (OR = 0.79, p<0.01) and irregularity (OR = 0.89, p = 0.02) in these infants. CONCLUSIONS: Pathways from pregnancy smoking to offspring behaviour are complex and multi-determined. These findings suggest that both exposure and maternal characteristics associated with pregnancy smoking status contribute to offspring behavioural patterns. Research that characterises differences between quitters and persistent smokers and examines the role of these differences in prediction of early vulnerabilities and problems in adaptation over time will be important for elucidating these pathways.

Anti-platelet agents and surgical delay in elderly patients with hip fractures.

PURPOSE: To assess the risk of surgical delay in elderly hip fracture patients on anti-platelet agents. METHODS: Records of 180 patients aged over 65 years with either an intertrochanteric or femoral neck fracture were reviewed. The clopidogrel group included 10 patients on clopidogrel alone and 11 others on clopidogrel and aspirin, whereas the control group included 69 on aspirin alone and the remaining 90 not on any anti-coagulants. The 2 groups were compared with regard to time to surgery, preoperative American Society of Anesthesiologists (ASA) score, pre- and post-operative haemoglobin levels, in-patient complication rates, duration of hospital stay, and 30-day mortality. RESULTS: In the clopidogrel and control groups respectively, the mean times to surgery were 7.2 and 2.1 days (p=0.03, t-test), the mean preoperative ASA scores were 3.35 and 2.8 (p=0.29, t-test), the mean preoperative haemoglobin levels were 119 and 115 g/l (p=0.5, t-test), the mean postoperative haemoglobin levels were 98 and 96 g/l (p=0.68, t-test), the mean durations of hospital stay were 7.4 and 3.1 days (p=0.02, t-test). The 30-day mortalities were 6/21 (29%) and 6/159 (4%) [p=0.0003, Fisher's exact test]. CONCLUSION: Surgical delay in elderly patients on anti-platelet agents with hip fracture was associated with higher mortality. Despite the risk of increased blood loss, we suggest early surgery be carried out by an experienced surgeon to expedite the operating time. Pooled platelets should be given intravenously one to 2 hours preoperatively.

Rethinking research in breast-feeding: a critique of the evidence base identified in a systematic review of interventions to promote and support breast-feeding.

OBJECTIVE: To appraise critically the relevance and value of the evidence base to promote and support the duration of breast-feeding, with a specific focus on disadvantaged groups. DESIGN: A systematic review was conducted of intervention studies relevant to enhancing the duration of breast-feeding; topics included public health, public policy, clinical issues, and education, training and practice change. A systematic search was conducted. Eighty studies met the inclusion criteria. Data were systematically extracted and analysed. Full results and recommendations are reported elsewhere. Here a critique of the evidence base--topics, quality and gaps--is reported. RESULTS: Many studies were substantially methodologically flawed, with problems including small sample sizes, inconsistent definitions of breast-feeding and lack of appropriate outcomes. Few were based on relevant theory. Only a small number of included studies (10%) were conducted in the UK. Very few targeted disadvantaged subgroups of women. No studies of policy initiatives or of community interventions were identified. There were virtually no robust studies of interventions to prevent and treat common clinical problems, or of strategies related to women's health issues. Studies of health professional education and practice change were limited. Cost-effectiveness studies were rare. CONCLUSIONS: Policy goals both in the UK and internationally support exclusive breast-feeding until 6 months of age. The evidence base to enable women to continue to breast-feed needs to be strengthened to include robust evaluations of policies and practices related to breast-feeding; a step change is needed in the quality and quantity of research funded.

Determination of geometric orientation of adsorbed cinchonidine on Pt and Fe and quiphos on Pt nanoclusters via DRIFTS.

Platinum nanoclusters modified with cinchonidine have been employed as 'quasi-homogeneous' catalysts for the hydrogenation of ethyl pyruvate and have demonstrated exceptional activities while the ee's of these systems are currently inferior to the traditional Pt/Al2O3 heterogeneous system. For the bulk systems it has been shown that the orientation of the modifier on the metal surface is a critical parameter influencing catalytically induced enantioselectivity. It has been speculated that the lower observed ee's for the nanocluster systems are a result of the modifier assuming an orientation unfavorable for inducing enantioselectivity due to the lack of large numbers of planar metal atoms. Using DRIFTS (diffuse reflectance infra-red Fourier transform spectroscopy) analysis of samples together with geometry optimization and IR modelling we have studied the orientation of cinchonidine on Pt and Fe nanoclusters and additionally the man-made ligand quiphos on Pt nanoclusters. It has been determined that cinchonidine can adsorb on Pt and Fe nanoclusters in both 'flat' and 'tilted' modes, while quiphos can be adsorbed on Pt only via the 'pi-bonded' mode. These studies thus provide an insight into modifier orientation on nanocluster surfaces that can be extended to a wide range of potential modifiers and facilitate a better understanding of the origin of enantioselectivity with these 'quasi-homogeneous' catalyst systems.

The 22-mm vs the 32-mm femoral head in cemented primary hip arthroplasty long-term clinical and radiological follow-up study.

A retrospective clinical and radiological analysis was performed on 117 patients (138 hips) with a mean age of 75 years and a mean follow-up of 11 years. The prostheses used were 2 similar monoblock femoral components with 22- and 32-mm head sizes; their effects on the wear of the high-density polyethylene cup were studied. Wear of component was determined by evaluating the standardized initial and follow-up radiographs. The mean rate of linear wear was higher in the 22-mm femoral head, whereas the volumetric wear was higher in the 32-mm femoral head. In both groups, volumetric wear was significantly correlated with cup lysis. Increasing body weight in both groups was associated with more volumetric wear. The radiological evidence of prosthetic loosening did not correlate well with clinical evaluation of the hip.

Improving services for disadvantaged childbearing women.

BACKGROUND: Tackling health inequalities is high on the political agenda of the Labour government. The government wants to reduce inequalities through policies based on evidence, the health of childbearing women and their babies being priority areas for action. National Service Frameworks (NSFs) are being set up to ensure high quality services for all groups. The External Working Group looking into maternity services for the Children's NSF seeks evidence upon which to plan strategies for all women, while focusing attention on the most disadvantaged. Wide differentials are noted between high- and low-income groups in the outcomes of pregnancy and the health of babies. The worst outcomes appear to be concentrated in small subgroups of disadvantaged women. AIM: To report on a review of studies of interventions improving perinatal outcomes for disadvantaged women, to inform policy and practice around the organization and delivery of statutory services in the UK. METHOD: We searched six relevant databases for reviews, intervention studies, audits and descriptions of services reporting outcomes for disadvantaged groups of women, published between 1990 and 2003. Synthesis was performed around what works and what does not work. Gaps in the evidence base were identified. RESULTS: We found limited evidence of effective and promising interventions for childbearing women from minority ethnic groups, women experiencing domestic violence, women with mental health illness and HIV infected women. Few studies were well-designed or powered to detect effectiveness. There were no studies of interventions for women prisoners, homeless women and travellers. CONCLUSIONS: Searching for intervention studies primarily by participant subgroup has brought in evidence from few well-designed studies on which to plan policy. Combining this approach with searching for intervention studies addressing behaviour like smoking, and needs like social support, may provide further evidence to tackle inequalities in the perinatal period.

New acetogenin peroxides from the Indian sponge Acarnus bicladotylota.

Two new cyclic peroxides (1 and 2) and the known metabolite 3 have been found in the organic extract of the Indian sponge Acarnus bicladotylota. The structure of the new products has been assured by chemical and spectroscopic methods. The absolute stereochemistry of 1-3 has been determined by Mosher's method on the semisynthetic derivative 4.

Expression of marker RNAs in Pseudomonas putida.

A broad-host-range vector that expresses a unique artificial RNA in Pseudomonas putida has been developed. This vector was derived from the plasmid pBBR1MCS and incorporates regulatory regions from the Escherichia coli ribosomal operon, rrnB. These include the promoters P1 and P2, and the terminators T1 and T2. The gene for the artificial RNA was derived from Vibrio proteolyticus 5S rRNA. The artificial RNA product accumulates to a level that is 10-20% of the total 5S rRNA in P. putida. The RNA product is not incorporated into ribosomes and has a minimal effect on cell growth rate. In contrast, when wild-type V. proteolyticus 5S rRNA was expressed from the vector, it was incorporated into ribosomes. It is expected that this new vector system will allow artificial RNA expression systems to be readily developed for a large variety of species.