onsdag 23 januari 2013

Sapropteriini, Tetrahydrobiopteriini

Redusoitu biopteriini (BH4) , jota kehon pitää pystyä valmistamaan, koska  kaikkien NOS-entsyymien aktiivisuudelle  se on välttämätön tekijä.

  • Suomalainen Wiki sanoo näin:
Tetrahydrobiopteriini, (BH4, THB) on luonnollisesti esiintyvä koentsyymi, joka on välttämätön joidekin aromaattisten aminohappojen hydroksylaasin toiminnalle.

Fenyylialaniinihydroksylaasi eli PAH löytyi ensimmäisenä.[1] Todettiin, että tetrahydrobiopteriinin puute saa aikaan harvinaisen aineenvaihdunnan häiriön, joka lisää veren fenyylialaniinipitoisuutta. Fenyylialamiinin kertyminen elimistöön aiheuttaa kehitysvammaisuutta ja muita vakavia terveysongelmia.

Tetrahydrobiopteriini ja Fe2+-ioni ovat tryptofaanihydroksylaasin toiminnalle välttämättömiä koentsyymejä [2] jotka vaikuttavat serotoniiniaineenvaihdunnan kautta muun muassa keskushermoston toimintaa.

Saunassa kudosten lämmetessä elimistöön syntyy tetrahydrobiopteriinia, jota tarvitaan verisuonten normaalin toiminnan ylläpitämisessä.
Tetrahydrobiopteriinista käytetään myös nimeä 5,6,7,8-tetrahydrobiopteriini.
Tetrahydrobiopteriinin kemiallinen kaava on C9H15N5O3, moolimassa 241,247 g/mol ja CAS-numero 17528-72-2.

  • Vuodelta 2007 on seuraava laaja artikkeli:
http://flipper.diff.org/app/pathways/info/170 
  • KUVA , Fenylalaniini, Tyrosiini, DOPA aineenvaihdunta alue
http://www.biochemj.org/bj/319/0947/bj3190947a05.gif
Myös: tryptofaanin aineenvaihdunta-alue

 Tryptophan hydroxylase (TPH) is an enzyme involved in the synthesis of the neurotransmitter serotonin. TPH catalyzes the following chemical reaction L-tryptophan + tetrahydrobiopterin + O2 5-Hydroxytryptophan + dihydrobiopterin + H2O It employs one additional cofactor, iron.
 Jos nukkuu hyvin ei voi suorittaa hyvä motorista prestaatiota samaan aikaan. 
http://cat.inist.fr/?aModele=afficheN&cpsidt=20533018
  • Myös tämä dihydropteriinista  BH2
http://www.ncbi.nlm.nih.gov/pubmed/17474729 
J Phys Chem A. 2007 May 24;111(20):4280-8. Epub 2007 May 3. Singlet oxygen (O2(1Deltag)) quenching by dihydropterins.

Source

Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CONICET, Boulevard 113 y 64 (1900) La Plata, Argentina.

Abstract

Pterins belong to a class of heterocyclic compounds present in a wide range of living systems. They participate in relevant biological functions and are involved in different photobiological processes. Dihydropterins are one of the biologically active forms of pterins. The photoinduced production and quenching of singlet oxygen (1O2) by a series of dihydropterins (7,8-dihydrobiopterin (DHBPT), 7,8-dihydroneopterin (DHNPT), 6-formyl-7,8-dihydropterin (FDHPT), sepiapterin (SPT), 7,8-dihydrofolic acid (DHFA), and 7,8-dihydroxanthopterin (DHXPT)) in aqueous solution at physiological pH ( approximately 7) were investigated, and the quantum yields of 1O2 production (PhiDelta) and rate constants of total quenching (kt) of 1O2 were determined.
Studied compounds do not produce 1O2 under UV-A irradiation and are very efficient 1O2 quenchers. The chemical reactions between 1O2 and dihydropterin derivatives were investigated, and the corresponding rate constants (kr) were found to be particularly high.
 The oxidized pterin derivatives, biopterin (BPT), neopterin (NPT), 6-formylpterin (FPT), and folic acid (FA), were identified and quantified during the reaction of 1O2 with DHBPT, DHNPT, FDHPT, and DHFA, respectively.
Besides the oxidation of the dihydropyrazine ring to yield the corresponding oxidized pterins, a second oxidation pathway, leading to fragmentation of the dihydropterin and formation of non-pterinic products, was identified. Mechanisms and biological implications are discussed.
PMID:
17474729
[PubMed - indexed for MEDLINE]

torsdag 17 januari 2013

tisdag 8 januari 2013

Vähäbakteerisesta ruoasta vuodelta 1993

Miten alentaa bakteerimäärää ruoassa?
Esimerkkiinä AJ Pattisonin  neutropeniadieetti vuodelta 1993. Täallinen oli tarkoitettu ensisijassa lapsille, joilla oli maligni veritauti, hoitona  sytostaatteja ja koko kehon säteilytys ennen luuydinsiirtoa, sillä hoidossa häviää valkosolutkin joksikin aikaa ja silloin immuunivaste on hyvin heikkona. bakteerien tuloa kehoon voi alentaa, katsomalla että ruoka ei tuo liikaa bakteereja mukanaan ja mutenmin on hygienisesti tehtyä. Pattisonin dieettiä on myöhemmin  modifioitu lievemmäksi, mutta tämä on hyvä pitää tallella tämäkin ohje pahan päivän varalta.
  • (Näitä periaatteita toistivat  myös 2000- 2001 dietetiikan luennoilla onkologiaan erikoistuneet  dietistit Ruotsissa:  
  • "Hedelmät tulee kuoria valmiiksi. 
  • Sormin poimittavaa ruokaa ei saisi käyttää.
  •  Eläviä bakteereja sisältävää ruokaa pitäisi välttää. 
  •  Ruoan valmistajan on pidettävä tarkka huoli käsien puhtaudesta .
  •  Syöpäpotilaille  kaikki ruoka, minkä potilas syö, sitä oikeaa ruokaa. Huono ruokahalu on vaikea asia syöpätaudissa ja hoidon sivuvaikutuksena)".

Alla oleva artikkeli on englantilainen:

LÄHDE: Pattison J Amanda. Review of current practice in clean diets in the UK. Journal of Human Nutrition and dietetics, 1993; 6; 3-11.

Introduction
Bone marrow transplant (BMT) can be an effective method of improving the prognosis of patients with resistant malignant diseases involving the bone marrow, usually leucemia ( Pachedly, 1983). Before infusion of the donor marrow, patients receive an intensive course of chemotherapy, usually combined with total body irradiation. This effectively destroys all the cells in the bone marrow, causing the patient to be free from disease and reducing the risk of graft rejection and graft-versus-host disease. However, the destruction of neutrophils leads to a diminished inflammatory response to infection (Bast, 1982, cited in Fisher, 1991). Lymphocyte levels are also depressed after total body irradiation, but can also be affected by malnutrition ( Fischer, 1991). Haffajee & Augburn ( 1985, cited in Fisher, 1991) found that the lymphocyte levels of patients with unresectable cancer of the oesophagus rose to normal when the patients achieved a positive nitrogen balance. This would suggest the use of supplementary feeding in such patients before and after transplantation. A complete enteral feed  (EN) should be considered over total parenteral nutrition (TPN) or an elemental enteral feed due to intestinal atrophy and overgrowth of gut bacteria. This is accelerated if the intestinal mucosa is damaged after intensive chemotherapy and total body irradiation ) Alexander, 1990; Barber et al. 1990).

Immunosuppression lasts for several weeks after transplantation and infection is the major cause of morbidity (Naiseef & Maki, 1981). Initially, the patient is usually maintained in closed cubicle or occasional laminar air flow (LAF) unit. Staff and visitors generally wear gowns, gloves and masks to minimize sources of infection from the hospital environment.

Food is one potential source of infection and there is usually some level of “clean diet” employed. This ranges from following basic food-hygiene guidelines to sterile diets used in conjunction with gut-sterilizing antibiotics. In addition to BMT patients, some control may be placed on food for other immunosuppressed patients, e.g. those having conventional chemotherapy.

The clean diet followed by BMT patients at Sheffield  Childrens Hospital  prior to the present review can be seen in Appendix 2. Additional information was given on suitable meal choices, individual portions available from catering and a suggested meal pattern.

At S. Hospital, in view of the restricted food choice imposed and the improved clinical management of BMT patients, colleagues in the haematology team questioned whether a clean diet was necessary for these patients or, indeed, if its use should be extended to all immunosuppressed patients.

In response, this review was undertaken which aimed to look at current practice in clean diet among UK BMT centres and to use the results together with discussion amongst collegues at S. Hospital to formulate new clean food guidelines.

Method
The dietitians at each of the 20 centres in the UK carrying out BMTs in children were asked for information on their current practice in “clean” diets. Diet sheets and/ or protocols were received from 16 of these centres.

Results
Table 1 is a collation of the information received, including 12 different diet sheets. Several centres use the information provided by the Manual of Dietetic Practice (Thomas, 1988)


Table 1
Food group (and frequency)


WATER
Tap-water (3)
Boiled tap-water (4)
Tap-water let run (3)
Sterile water only (2)
Boiled tap or sterile (2) 
 MINERAL WATER
Bottled only (1)
Canned only (1)
Sparkling only (1)
Any (1)
Evian, Perrier only (1)
No mention (7)
    DRINKS
COFFEE
Sachets (4)
Boiling water(2)
No mention( 6)
TEA
Tea bags (3)
Irradiated (1)
Boiling water (2)
No mention (6)
  SOFT DRINKS
Canned or bottled (7)
Sparkling only (2)
Repasteurized squash (1)
Cordial only (2)      
DAIRY PRODUCTS
MILK
Sterilized only (6)
Pasteurized (6)
  DAIRY PRODUCTS
YOGHURT
Any (2)
No live yoghurt (4)
Long-life only (1)
No mention (4)
    CHEESE
Cooked only (1)
Processed only (3)
Cooked/processed only (3)
No blue or soft (3)
No mention (2)

  DAIRY PRODUCTS
BUTTER

Individual portion (7)
Any-refrigerated (4)
Autoclaved (1)      
MEAT and FISH
Well cooked (10)
Tinned (6)
Frozen (4)
No cold meat (1)
Good quality (2)
  EGGS
Well cooked (9)
Pasteurized (1)
Ni mention (2)
  FRUIT
Tinned only ( 3)
Peeled-raw allowed (3)
No raw (6)
No dried (4)
  VEGETABLES
No salad/ raw
Cooked only (10)
Frozen/tinned only (2)       
BREAD
Any (3)
Fresh loaf /3)
Toasted (3)
Double-baked (1)
  Breakfast cereal:
Any (1)
Individual portion (9)
No dried fruit/ nuts/ sugar coated (1)
No mention (1)
  BISCUITS, CAKES
Any (2)
Individual portions (6)
Plain only (1)
No cream cakes (1)
Home-baked only(1)
No cakes (1)  
   CHOCOLATES SWEETS
Individual portions (5)
Double-wrapped (2)
No nuts/dried fruit (1)
No chocolate (3)
No mention(1)      
DESSERTS
Tinned/individual portions (4)
No custard/blancmange (1)
Freshly cooked (2)
No instant desserts (2)
No mention (1)
    JAM, SAUCES, SUGAR etc
Individual portions (4)
Irradiated pepper (1)
No mayonnaise (1)
Any (3)
No mention (5)           

As can be seen, individual portions of butter, salt, sauces, etc. and individually wrapped biscuits, cakes, desserts and breakfast cereals are favoured by most centres. This minimizes wastage and avoids the use of leftover food.

Meat products and cold meats are generally avoided as, they are a common source of infection, particularly if stored incorrectly.

Centres which use only toasted bread do so to kill any surface yeasts. Pepper and spices must generally be cooked as they are a major source of bacterial spores.

There appears to be no consensus of opinion regarding the use of tap-water and mineral water. Sterile water is used by four centres and tap-water is used by four centres. Boiled water is the most popular, but other centres use untreated tap-water or tap-water which has run for several minutes.

The bacterial content of mineral waters has been questioned (DHSS, 1988), but several centres do use them. Again, no common patterns within the type of water used can be seen.  Unboiled mineral water or tap-water should certainly not be given to healthy infants, but their use for immunosuppressed children requires further clarification. There is some support for the view that carbonated drinks tend to have a lower bacterial count and this presumably forms the basis of the recommendation to use sparkling drinks.

Cooking methods
Table 2 shows the methods of food preparation for BMT patients. The Manual of Dietetic Practice recommends the use of conventional cookers and especially pressure-cookers, with a minimum core temperature of 70 degrees C. One centre encourages the use of slow cooking, e.g. stewing, braising and roasting, to kill bacteria most effectively. Only one centre mentions the use of microwave ovens; there they are used only for reheating cooked food on the ward.  Although most centres use conventional methods for cooking, a diet cook may prepare the food separately; it is cooked quickly and thoroughly and served immediately to minimize multiplication of bacteria.

Instruction for ward staff
Only three centres included instructions for ward, including preparation for eating, storage and service of food and treatment or disposal of food and utensils after each meal.
At S Hospital, a meal is served as soon as it is cooked and transferred from a covered plate to a clean plate inside the cubicle. All crockery and cutlery are soaked in a sterilizing fluid after washing, rinsed and stored in the cubicle, together with a selection of individually packaged snacks and vacuum-packed soft drinks.
Other centres vary in their degree of hygienic practice. The centre employing the sterile diet has its own housekeepers working in the LAF kitchen.

Information for home
At S Hospital, children may occasionally be discharged when their neutrophil count is >1x10E9/L. As this is below the normal range of 2.5- 7.5x10E9/L, some care with food is still necessary. Advice is given on ensuring food is as fresh as possible and refrigerated as necessary, not damaged or overripe, that food should be prepared in clean condition and that any food requiring cooking must be cooked thoroughly. Take-away food is not encouraged.
The Manual of Dietetic Practice offers similar advice, but states that no soft or raw eggs should be used, fruit and vegetables should be skinned and chilled cabinet foods should be avoided.
Three centres included literature for patients going home.
 One or more of these centres advises against the following foods:
Poultry, cold meat, shellfish, raw eggs, soft and blue cheeses, dried fruit, raw vegetables, fresh cream and tap-water.

Dietary supplements
At S Hospital, commercial tube feeds and ready-prepared sip feeds without additional ingredients are used wherever possible to avoid contamination. Feeds are stored and prepared if necessary in a special feed unit under very clean conditions. The bottle or carton should be opened in the cubicle and either refrigerated in a sealed container for up to 24 hr or discarded if not used immediately. Prior to opening, bottles of prepared feed must be kept refrigerated. Information on the specific use of supplements was not received from other centres.

Table 2

Method     Number of centres     Comment      
Main kitchen
Conventional cooking
Reheat in microwave oven    .
11 centres
1 centre     Diet cook generally follows detailed instructions      
Cook chill    1 centre    Only up to day of transplant      
Ward kitchen    2 centres     One used for BMT food preparation only       
Gamma-irradiated/tinned food prepared in LAF uni     1 centre     Sterile diet used for BMT patients   

Discussion
Although the design of the survey provides only a limited amount of information, that which was received demonstrates that the level of restriction varies enormously between centres. The differences appear to be based on availably facilities and the individual views of staff. This is the case at S Hospital, where there are two closed cubicles available on the ward and very accommodating catering staff. Stricter measures have not been deemed necessary by the haematology team in the past. The use of LAF units as opposed to closed cubicles has decreased in popularity due to financial constraints and more effective antibiotic therapy. Studies have shown that total isolation can lead to low morale and poor appetite (Driedger & Burstall, 1987) and may not be more successful in reducing infection rates /Yates & Holland, 1973) when appropriate antibiotics are used.

Bacterial contamination
 is by far the commonest cause of food poisoning with
·    Salmonella causing 80-90% of cases in the general population, followed by
·    Clostridium perfringes and
·    Staphylococcus aureus.
High risk foods
( those which support multiplication of pathogens in  the state they are to be eaten) are listed as cooked meat and poultry, dairy products, cooked eggs and egg products, shellfish and cooked rice.

Raw vegetables

 have also been implicated as a source of infection for immunosuppressed patients from
·    Pseudomonas aeruginosa
·    Escherichia coli and
·    Klebsiella species
(Shooter et al 1971; Kominos et al. 1972; Mutton et al 1980)
Contamination may occur during preparation of salad vegetables suggesting a need for scrupulous kitchen practice.

Bacterial testing of food
 in US centres tend to be carried out only in LAF environments (Dezenhall et al, 1987) and was taken into account in only some of the centres surveyed here. The microbiology department at S Hospital does not feel that foodborne pathogens are an important source of infection in BMT patients and does not carry out routine microbiological testing of food. 

One classification of the food to be “high risk”
Driedger  et Burstall (1987) classified food according to bacterial levels and found the following foods to be “high-risk”: salads, fresh fruit and vegetables, non pasteurized dairy products and prepared snacks, desserts and condiments.

The number of organism that must be swallowed by a patient for intestinal colonization varies according to antibiotic therapy and the underlying disease. Animal studies have shown that in lowered resistance, only 10-100 organisms are needed for colonization, compared with  1 000 000 organisms in unimpaired resistance ( Van der Waajj et al 1972). After antibiotic therapy the intestine may be colonized with new pathogens after relatively few organisms have been ingested (Remington et Schimpff, 1981). The optimal temperature for multiplication of bacteria is 37 degree C and multiplication is rapid between 20 and 50 degree C. Food should be kept below 10 degree C or above the critical temperature 63 degrees C. Above this temperature, bacteria can no longer multiply. The Manual of Dietetic Practice recommends a minimum core temperature of 70 degrees C.

Ovens should be preheated
 to a minimum temperature of 200 degrees  C to raise the temperature of the food quickly. If food is to be boiled, e.g. vegetables, the water should be boiling before food is added to it.
Pressure-cooking is a good choice as long as the food is served immediately after cooking.
 The use of microwave ovens
to cook food for BMT patients remains controversial. Their use was mentioned by only one centre surveyed here, which used microwave oven only for reheating cooked food. Microbes may only be inactivated in the presence of water, so dry foods may not be cooked effectively by microwave (Vela et Wu, 1979). In addition, Page et Martin, 1978, found that the survival
·    Escherichia coli and
·    Streptococcus  cerevisiae on the inner surfaces of microwave oven was high when compared with the same organism in food.

Therefore, it is essential to disinfect the oven, especially if used for immunocompromized patients.
Fruuin et Gethertz (1982) found that bacteria were not killed as effectively by the rapid increase in temperature in microwave cooking as in conventional cooking, where food is held at high temperature for a long time.
However, Dreyfuss et Chipley (1980) found that microwave ovens had a destructive effect on Staphylococcus aureus due to radiation, in addition to the thermal effects found on conventional ovens.

There has been little documented evidence on the use and effectiveness of “clean”  diets. Generally, there are four different levels of restriction.
Recently established centres in a US survey ( Dezenhall et al 1987) tended to use a modified ward diet ( normal diet excluding fruit and vegetables) and four centres had changed from sterile diet to a low-bacteria or modified ward diet. Reasons for the move towards less strict dietary procedures included limited availability of individual portions of sterile foods, lack of standardized recipes and low patient acceptance of autoclaved foods.
 Preisler et al (1987) found a sterile diet afforded little or no advantage over a low-microbial diet and Yales et Holland (1973) showed a decreased incidence of Pseudomonas infections in both patients on a sterile diet and on a low-microbial diet.
Naiseef et Maki (1981) stated that it was possible for the simple measure of providing well-cooked food to provide considerable protection against endogenous infection caused by hospital acquired organisms.

Pizzo et al (1982) found that food selection became the focal point for patient frustration and also affected patient compliance with other medical procedures. A wider food selection added pleasure and variety to patient meals especially children.

Conclusion
Following the survey of current practice, discussions between the consultant haematologists, oncologists, microbiologists, ward staff, catering staff and dietitian reviewed the advice given to BMT patients at S Hospital. Several other factors were taken into account.
(1)    There had been no record of food related infections in any immunosuppressed patient at the hospital.
(2)    It was felt that the restrictions imposed by the clean diet made it difficult for the children to enjoy their food.
(3)    It was felt that any advice given to patients undergoing BMT should be extended to any child undergoing chemotherapy as they would all be immunocompromised to some extent. Practically, this would be possible with new guidelines.
(4)    The temperature of the food served from the ward trolley is regularly monitored to be higher than 63 degrees C.  and therefore it was felt unnecessary to provide individual meals.

As a result. the advice now given is more in line with a more relaxed diet used in other centres for use at home. The advice sheet is given to all new patients on the oncology ward at the start of their treatment. The guidelines are to be continued on discharge.
Evaluation of patient acceptance and infection rates following the implementation of these guidelines will be carried out in the future.
 ( Appendix 1,2,3, ei ole kirjoitettuna tässä)