Fungal quinones: diversity, producers, and applications of quinones from Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium.

Quinones represent an important group of highly structurally diverse, mainly polyketide-derived secondary metabolites widely distributed among filamentous fungi. Many quinones have been reported to have important biological functions such as inhibition of bacteria or repression of the immune response in insects. Other quinones, such as ubiquinones are known to be essential molecules in cellular respiration, and many quinones are known to protect their producing organisms from exposure to sunlight. Most recently, quinones have also attracted a lot of industrial interest since their electron-donating and -accepting properties make them good candidates as electrolytes in redox flow batteries, like their often highly conjugated double bond systems make them attractive as pigments. On an industrial level, quinones are mainly synthesized from raw components in coal tar. However, the possibility of producing quinones by fungal cultivation has great prospects since fungi can often be grown in industrially scaled bioreactors, producing valuable metabolites on cheap substrates. In order to give a better overview of the secondary metabolite quinones produced by and shared between various fungi, mainly belonging to the genera Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium, this review categorizes quinones into families such as emodins, fumigatins, sorbicillinoids, yanuthones, and xanthomegnins, depending on structural similarities and information about the biosynthetic pathway from which they are derived, whenever applicable. The production of these quinone families is compared between the different genera, based on recently revised taxonomy. KEY POINTS: • Quinones represent an important group of secondary metabolites widely distributed in important fungal genera such as Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium. • Quinones are of industrial interest and can be used in pharmacology, as colorants and pigments, and as electrolytes in redox flow batteries. • Quinones are grouped into families and compared between genera according to the revised taxonomy.

The mechanisms of crystal growth inhibition by organic and inorganic inhibitors.

Understanding mineral growth mechanism is a key to understanding biomineralisation, fossilisation and diagenesis. The presence of trace compounds affect the growth and dissolution rates and the form of the crystals produced. Organisms use ions and organic molecules to control the growth of hard parts by inhibition and enhancement. Calcite growth in the presence of Mg2+ is a good example. Its inhibiting role in biomineralisation is well known, but the controlling mechanisms are still debated. Here, we use a microkinetic model for a series of inorganic and organic inhibitors of calcite growth. With one, single, nonempirical parameter per inhibitor, i.e. its adsorption energy, we can quantitatively reproduce the experimental data and unambiguously establish the inhibition mechanism(s) for each inhibitor. Our results provide molecular scale insight into the processes of crystal growth and biomineralisation, and open the door for logical design of mineral growth inhibitors through computational methods.

TMEM16A is a Ca(2+) -activated Cl(-) channel expressed in the renal collecting duct.

AIM: In the renal collecting ducts, ATP stimulates a Ca(2+) -activated chloride current. The identity of the channel responsible for the current under physiological conditions is not known and it was hypothesized that TMEM16a is a relevant candidate in the renal collecting duct. METHODS: The cortical collecting duct cell line M-1 was used as a model of the collecting duct. The ATP induced Ca(2+) signalling was imaged in cells loaded with Ca(2+) -sensitive fluorescent probes using confocal laser-scanning fluorescence microscopy. Chloride current was determined by mounting M-1 cell layers in Ussing chamber. The expression of TMEM16a in human kidney was tested by immunohistochemistry. RESULTS: M-1 cells displayed a transient increase in intracellular Ca(2+) concentration in response to 100 nm ATP. This response was completely blocked by addition of 100 µm suramin, indicating that ATP signals through purinergic P2 receptors. Apical addition of 100 nm ATP induced a Cl(-) current, which was blocked by suramin, DPC and the cysteine-modifying compound MTSET. M-1 cells were found to express TMEM16a at the mRNA and protein level. Functionally, it was found that knock-down of TMEM16a expression in M-1 cells inhibited the ATP induced Cl(-) -current. In human and mouse kidney sections, TMEM16a protein expression was localized to the collecting duct, and TMEM16a was found to be excreted in human urinary exosomes. CONCLUSION: TMEM16a is a Ca(2+) -activated Cl(-) channel expressed in the collecting ducts.

Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort.

BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

[Sumatriptan treatment of migraine in general practice. A randomized, double-blind, placebo-controlled cross-over study]. / Sumatriptan ved migraene i almen praksis. En randomiseret, dobbeltblind, placebokontrolleret overkrydsningsundersøgelse.

Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included. The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo and the alternative medication for the second attack (cross-over). When sumatriptan was compared to placebo, significantly more of the 209 evaluable patients reported headache relief at one hour (56% v 8%, p < 0.001) and two hours (62% v 15%, p < 0.001) after the first injection. Resolution of nausea, photophobia and phonophobia was significantly more common in patients on sumatriptan than on placebo (p < 0.001 for all comparisons). The adverse events were usually transient and of mild or moderate severity, although, three patients withdrew due to adverse events. Ninety-five percent of patients evaluated by a neurological research fellow met the International Headache Society's criteria for migraine. In general practice, sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine.

[A comparison of 2 new rapid methods for determination of HbA1C concentration in patients with diabetes mellitus]. / En sammenlignende undersøgelse af to nye hurtigmetoder til bestemmelse af HbA1c-koncentrationen hos patienter med diabetes mellitus.

We have evaluated a new immunoturbidimetric assay (DCA 2000 HbA1c system, Bayer, Denmark) for determination of HbA1c. The aim of the study was to evaluate accuracy, precision and feasibility for the DCA 2000 method when employed in a diabetes centre by a technical assistant and at a general practitioner's by non lab staff. The results were compared with a high performance liquid chromatographic method (HPLC, AUTO A1C, Kyoto Daiichi Kagaku Co., Kyoto, Japan) which is the current laboratory method, and therefore used as reference. Assay time for the DCA 2000 method was nine minutes, while the HbA1c result was displayed within four minutes by HPLC. Blood samples were drawn after informed consent from 118 patients during a period of two months at the out-patient clinic of the Dept. of Paediatrics, Glostrup Hospital (n = 67) and at a general practitioner's (n = 51). Each sample was analyzed twice by each method on two consecutive days. In the HbA1c range from four to 14% (n = 67) the average within-assay precision (SD) for the HPLC method was 0.13%, whilst it was 0.23% for the DCA 2000 method (p < 0.001). The within-assay precision was low and acceptable, and for both methods it was independent of the current HbA1c concentration. For the DCA method precision was almost similar (p > 0.07) when carried out by a technical assistant (SD: 0.20%) and by non lab staff (SD: 0.25%). Interbatch variations for HbA1c results investigated with two different batches of reagents within a month were SD 0.30% (HbA1c range: 4.9-5.9%, n = 30) and SD 0.44% (HbA1c range: 10.5-12.1%, n = 30) for these two preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Oral contraceptives: knowledge and compliance]. / P-piller: viden og komplians.

One hundred and twenty (120) women, taking contraceptive pills, underwent a structured interview with a view elucidating their knowledge of the physiology of menstruation, the action and side effects of contraceptive pills and their compliance in the taking of contraceptive pills. The most important sources of information were the medical letters in magazines and the women's own doctors, while the teaching in the Folkeskole (primary and lower secondary school) had not had any major influence on the level of information. Well over one third of the interviewed women knew the most important action mechanism of the contraceptive pill, and half of the women could give a satisfactory explanation of the physiology of menstruation. Twenty-four percent (24%) thought that pregnancy could not occur until 1-2 months after the woman had ceased taking the pill. There was high compliance among the women i.e. that their behavior was correct when they had forgotten to take one or two contraceptive pills, when bleeding was irregular, and when beginning on a new package of pills. Eighty-three percent (83%) had experienced side effects that could be related to contraceptive pills. The investigation shows that there is a need for more efficient information about the effects of the Pill and about the physiology of menstruation.

PIP: 120 women using oral contraceptives (OC) participated in a structured interview with a view to establish their knowledge of the physiology of menstruation, the action and side effects of contraceptive pills, and their compliance in taking OCs. The most important sources of information were the medical columns in magazines and the women's own doctors, while only a small number received their information from the instruction in the Folkeskole (primary and lower secondary school). 39% of the interviewed women knew the most important action mechanism of the contraceptive pill, i.e., the suppression of release of eggs. 43% of the women could give a satisfactory explanation of the hormonal physiology of menstruation. 24% thought that pregnancy could not occur until 1-2 months after the woman had ceased taking the pill, and 64% stated that one can get pregnant right after halting OC use. There was a significant negative correlation between social status and the scoring of information (r = 0.24, p 0.01) and a significant positive correlation between age and information scoring (r = 0.38, p 0.001). Information level was higher among women in steady relationships than among women without steady partners (r = 0.27, p 0.01), and it increased with the number of pregnancies (r = 0, 18, p 0.05). There was a positive significant correlation between the duration of pill taking and the information score (r = 0.31, p 0.001). The median score was 18.0. There was high compliance among the women, i.e., their behavior was correct when they had forgotten to take one or two contraceptive pills, when bleeding was irregular, and when starting on a new package of pills. 48% had forgotten to take their pills at some time. 83% had experienced side effects that could be related to contraceptive pills. 30% had minor menstrual pain, and in 22% the amount of bleeding diminished. The investigation shows that there is a need for efficient information about the effects of the pill and about the physiology of menstruation.

[Indicators of coronary risks--attitude, knowledge and behavior. An interview study among 917 men and women aged 25-44 years]. / Koronare risikoindikatorer--holdning, viden og adfaerd. En interviewundersøgelse blandt 917 maend og kvinder i alderen 25-44 år.

The purpose of this study was to clarify whether there was any agreement between knowledge about coronary risk factors, attitudes to individual prevention of coronary heart disease and preventive health behaviour. In particular the differences between males and females were examined. A total of 749 persons ranging in age between 25 and 44 (that is 82% of a random group of 917 persons) were interviewed in this cross sectional study. Physical inactivity, smoking and fat consumption were used as behaviour related risk factors. Generally, young adult Danes had a poor knowledge and poor health behaviour related to coronary heart disease in spite of their positive attitudes towards prevention. The study indicated that neither attitudes nor knowledge were correlated to preventive health behaviour. Women had better health behaviour patterns than men despite the same amount of knowledge and attitudes. In the above mentioned connexions, men showed positive correlation while no correlation existed for women.