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Introduction: Paracetamol is the most common medicine used as painkiller in the world. Since it has been on the market for a very long time it has been thought to be one of the safest medicines to use during pregnancy. Many women use this medicine for different indications during pregnancy thinking it is safe for the fetus. However, the mechanism of action for paracetamol is still unknown and therefore there is no information about how it could affect the fetus. Objective: To study paracetamol safety during pregnancy and its effect on the fetus and behaviour in childhood. Method: The information search for this literature study has been done through searching for different articles in the database pubmed. In these articles, pregnant women who used paracetamol during pregnancy have been analysed to see the effect on their children. Result: Different articles used in this literature study have shown an association between prenatal paracetamol exposure and behavioural problems in children. One study shows that if paracetamol is used during pregnancy the risk increases to get a Hyperkinetic disorder, HKD diagnosis (Hazard ratio (HR)= 1,37; 95% confidence interval (CI), 1,19-1,59), similarly the risk to get an ADHD-diagnosis increases (HR=1,29: 95% CI, 1,15-1,44). Discussion: The association between prenatal paracetamol exposure and behavioural problems has been shown in different studies made om pregnant women even though the exact mechanism is still unknown. Changes in children’s epigenetics seem to be associated with prenatal paracetamol exposure. Changes in DNA-methylation of genes previously linked to ADHD have been detected.   Conclusion: Prenatal paracetamol exposure seems to be associated with child behavioural problems. Therefore, paracetamol may not be a completely safe medicine in pregnancy and all pregnant women should have this information available to avoid unnecessary use especially during the second and third trimester. / Introduktion: Under graviditeten kan kvinnan få olika besvär och tillstånd som leder till att hon behöver behandlas. Paracetamol är det läkemedlet som används mest och är oftast lättast att få tag på då det säljs receptfritt. Läkemedel bör användas med största möjliga försiktighet då de flesta läkemedlen kan nå fostret via placentan. Eftersom paracetamols verkningsmekanism har varit okänd har inte några risker kunnat förutses hos foster. Syftet: Denna litteraturstudie har gjorts för att samla tillräckligt med information för att kunna besvara frågeställningen som är om paracetamolanvändning under graviditeten kan påverka fostret och barnets utveckling senare i livet. Metod: I denna litteraturstudie har information sökts genom att identifiera studier som har gjorts på gravida kvinnor och deras barn. Sökningarna har gjorts via pubmed och 6 originalartiklar har valts för att studera paracetamols effekt på fostret och senare effekt på barnet. Resultat: Flera studier på gravida och barn har visat association mellan paracetamolanvändning och barnens beteendeproblem. Hos kvinnor som använde paracetamol under graviditeten höjs risken för barnet att få en HKD (Hyperkinetic Disorder) diagnos (hazard ratio (HR)= 1,37; 95% konfidensintervall (CI), 1,19–1,59) och ADHD-diagnos (HR= 1,29; 95% CI, 1,15-1,44). Diskussion: Studierna påpekar associationen mellan paracetamolanvändning prenatalt och förhöjd risk för beteendeproblem hos barnen. Varje studie har tagit med olika confounders som kan bidra till ökad risk för beteendeproblem hos barnen. Att paracetamol kan associeras med beteendeproblem hos barnet kan inte uteslutas. Paracetamol borde användas under en kort period och enligt läkares ordinationer för att undvika komplikationer. Slutsats: Associationer mellan paracetamolanvändning under graviditeten och barns beteendeproblem senare i livet verkar existera även om de inte kan bekräftas helt säkert. Försiktighet borde iakttas när det gäller paracetamolanvändning under graviditet. Kvinnor borde få information för att undvika onödig användning av paracetamol under graviditet.

<p> Phenylketonuria (PKU) is an inborn error of metabolism characterized by a loss of phenylalanine hydroxylase activity; an enzyme that metabolizes phenylalanine to tyrosine. Phenylalanine ammonia lyase (PAL) is currently being evaluated as a possible therapy for the management of PKU. PAL catalyzes the conversion of phenylalanine to transcinnamic acid (TCA). Our proposed therapy involves encapsulation of PAL enzyme in ethyl cellulose microcapsules using the spray drying method. PAL activity is markedly reduced due to product inhibition. We hypothesized that the addition of albumin to the PAL reaction mixture would bind the TCA and prevent it from inhibiting PAL. In the first phase of our research, we developed an HPLC assay to quantitate phenylalanine and TCA in the presence of albumin. In the second phase, we determined that albumin completely alleviated product inhibition and enhanced PAL activity. Subsequent ultrafiltration studies showed that albumin acted by extensively binding to and sequestering TCA. PAL microcapsules will be taken orally. In the final phase, we studied the activity of encapsulated PAL in simulated GIT conditions to evaluate the ability of microcapsules to protect PAL enzyme against pH and protease mediated degradation. The activity of encapsulated PAL was lower than an equivalent amount of free PAL possibly due to diffusional limitations to the entry of phenylalanine into the microcapsules. Encapsulation of PAL in ethyl cellulose microcapsules did not protect against acidic pH mediated reduction of PAL activity or pepsin mediated proteolytic degradation. </p><p>

Between 1981 and 1982 the Banjarmasin Quadrangle in South-East Kalimantan was mapped by the Geological Research and Development Centre, Bandung at the scale of 1 : 250,000. This thesis reports the results of a follow-up study to the mapping programme, which was directed towards determining the age, origin and tectonic evolution of the Pre-Tertiary rocks which form the Meratus Mountains in the eastern part of the Banjarmasin Sheet. The study consists of detailed field-mapping of Pre-Tertiary rocks in well exposed river sections at the scale of 1:10,000. Measured sections of sedimentary units were made and all structural features were recorded. A comprehensive collection of rock samples was made for laboratory studies. Thin sections were used to determine the composition and origin of sedimentary and igneous rocks. Macro-and microfossils have been examined to determine the depositional environments and the ages of the sedimentary units. From these studies the Pre-Tertiary rocks are divided into a number of tectonostratigraphic units, whose age, origin, structural and tectonic evolution has been determined as far as possible. This information has been used to compile a synthesis of the tectonic development of the Meratus Mountains in the context of plate tectonics and the development of the western Indonesian region. Isotopic and palaeontological dating has shown that the units exposed in the Meratus Mountains range in age from Early Cretaceous to Early Palaeocene. The oldest unit is the Paniungan Formation of Berriasian to Barremian age. It grades upward into the Upper Barremian to Lower Aptian Batununggal Formation. These formations are interpreted as shelf to slope sediments. It is suggested that shortly after deposition, most parts of the shelf to slope sediments were juxtaposed by strike-slip faulting with oceanic crust now represented by the Meratus Ophiolite Complex. Subduction generated a calcalkaline volcanic arc which then collided with the Sunda continent in the Cenomanian time. This collision zone was disrupted and sliced by strike-slip faults, forming a pull-apart basin within it. The absence of Palaeocene to Lower Eocene deposits reflects uplift, subsequently followed by rifting, regional subsidence and deposition of an Eocene-Miocene transgressive sequence. The present configuration of the Meratus Mountains resulted from late Middle Miocene and Plio-Pleistocene tectonic events.

Archaean rocks of the area make up three depositional series which are separated in time one from another by periods of folding. The oldest rocks, exposed in the southern areas, consist of marine-laid basic lavas overlain by felsic volcanics and clastic sediments, all sheared and folded in a northwesterly direction. During the folding, regional metamorphism to the greenschist and amphibolite facies and intrusion of gabbro and ultrabasic rock, took place. The medium-aged rocks were deposited in a broad geosyncline which deepened to the north. In the central parts of the area, shelf facies deposits consist of basic lavas overlain by felsic agglomerate and coarse clastic sediments, but northward these rocks give way to uniformly banded fine clastic sediments deposited in a deeper sea environment. During the later stages of volcanism and sedimentation the rocks were folded synchronously along north-south and approximately east-west lines and metamorphism to greenschist and amphibolite facies took place. Domal structures controlled the locations of volcanic centres, igneous intrusion, and orebodies. The youngest group of rocks, which occurs in the northwestern area, was folded along dominantly east-west lines. Metamorphism of the original sedimentary rocks to gneisses of the high amphibolite facies may have taken place at this time. Faulting and the related intrusion of diabase dykes along north-south, northeasterly and northwesterly lines took place as uplift occurred in the northern areas during Proterozoic time. Widespread, severe retrograde metamorphism accompanied the faulting. Glacial, glacial-lacustrian, and fluvio-glacial deposits of pleistocene age now cover most of the bedrock to depths which range up to 400 feet.

Aim: The aims of the study were to compare the effects on depressive symptoms and insomnia between agomelatine and SSRIs/SNRIs in adult patients with major depression disorder. Method: Materials were collected from the database Pubmed and selected through the aims of the study and certain selection criterias. It was required that the studies fulfilled at least one of the study´s aims to be eligible for inclusion. Eight randomised clinical trials were included in the study. The results from the studies were compared according to statistical and clinical significance. Results: Depressive symtoms were reduced both with agomelatin and SSRIs/SNRIs. Generally the rates of respone and remission were similar of agomelatine and SSRIs/SNRIs. There were advantages for agomelatine in the individual studies concerning rates of respone and remission. Six of the included studies investigated the effect on insomnia. In a majority of these studies agomelatine caused a statistically significant improvement compared to SSRIs/SNRIs. Clinically, both agomelatine och SSRIs/SNRIs improved most of the variables related to insomnia that were examinated according to patient-reported outcome results. Conclusion: Statistically both SSRIs/SNRIs and agomelatine achieved similiar effects on depressive symptoms. In the majority of the included studies that examinated effect on insomnia agomelatine showed a statistically significant improvement compared to SSRIs/SNRIs. Clinically, agomelatine is viewed as a viable option for adult patients with major depressive disorder with unsuccessful response or remission from SSRIs/SNRIs. A similiar clinical relevance were shown for agomelatine and SSRIs/SNRIs concerning improvement of insomnia according to patient-reported outcome results.

Drugs are an essential part of health care today. They improve and extend the lives of many people. If drugs are wrongfully combined or given in inaccurate dose, it may lead to poorer quality of life, hospital admissions and even deaths. Drug-related problems cost society a large amount of money each year. To minimize these problems, there are now electronic decision supports that doctors and pharmacists can use. At all pharmacies in Sweden, the electronic expert support system available. The EES analyzes electronic prescriptions and doses prescribed and indicates if it detects any potential drug-related problems. Such risks may be that the customer has several drugs with the same effect, drug interactions or that the drug is inappropriate due to age. For children, there are special warnings that may be that the doctor on the prescription has prescribed a higher dose of the drug against what is commonly given to a child. The purpose of the study was to investigate pharmacy customers view of and knowledge about pharmacist use of EES. Data were collected via surveys for 100 hours at several different pharmacies in Sweden. The vast majority of pharmacy customers did not know of EES, only one fifth of the survey respondents knew what EES meant. Consent from the customer is required for the pharmacist to use EES when dispensing drugs and one third of the customers did not know if they agreed to this or not. Half of the customers did not know if the pharmacist used EES when the drugs were dispensed. Most of the customers also did not know whether their drug dispensing would be safer, if they would get better advice if the EES was used or if they wanted the pharmacist to use EES as a tool in the prescription expedition. The study shows that pharmacy customers' views and knowledge about the use of  EES by pharmacists are limited. The reason for this may be that it takes extra time for pharmacists to inform customers about what EES means and ask them for consent that the expert support should be used in the prescription expedition. Many times the pharmacist is experiencing a shortage of time to do this. The reason why EES is not used may be because the pharmacist does not feel adequately educated in how the decision support works and therefore chooses not to use it. It may also be due to communication difficulties such as language problems, hearing impairment or the customer's reduced cognitive ability. There is a need for communicative improvements between the customer and the pharmacist so that the pharmacists will increase the use of EES when dispensing drugs. There is also a need for pharmacists to get education in how EES works and how to use the decision support. If this is done, it will provide the customer with a better drug use with reduced risk of side effects and drug-related problems.

Abstract Pharmacists have for many years been an important part of health care. They have rescued many people from diseases and poisoning. It´s important that they ensure the right drug, dosage and administration in right time for each customer. Elderly people usually have more prescribes than younger which increases the risk of interactions. Poor compliance may result in increased morbidity or premature death. There are several reasons why treatment is not followed. Lack of information about the treatment of disease or information about the medications for both indication and side effects are some of them At all pharmacies in Sweden, EES, Electronic Expert Support, is available. The introduction of e-prescription in the 21st century has enabled an additional safety check for the pharmacist, using Electronic Expert Support (EES) for dispatching prescriptions. The current recipe is compared with other prescriptions where there are withdrawals and the prescriptions where there should be pharmaceuticals left to consume. If there is a risk of incorrect dose, double prescription, age warning, interactions, gender specific or if drug affecting disease, a signal is given at EES control showing strength and action that may, should be done. The purpose of the study was to investigate customers perception of advice at the pharmacy and if the use and knowledge of the EES (Elektroniskt Expertstöd) differed between different age groups. The survey was conducted using data collection from seven pharmacies located in five locations spread across Sweden. The collection was conducted for about 100 hours and generated in 277 participants. All participation was voluntary and anonymous. The participants were divided into three age groups: 40 years or younger, 41-60 and over 60 years. The collected data was analyzed by using IBM SPSS and a chi2 test was performed to see if there were any significant differences between the age-groups. The result was compiled and demonstrated in excel diagrams. There was no significant difference between the groups in terms of safety and information they received about their drugs. Most people received information about their medicines by the doctor, pharmacist or by reading the package leaflet. However, there was some difference regarding the use of the Internet in a search for information retrieval among those over 60 years. This may be due to lack of internet knowledge or physical impairment. There was also a significant difference when it came to the question of calling 1177 for information on medicines, where people 40 years or younger, called more often than other groups. This may be because they usually have younger children and may need advice regarding illness or injuries. There was a significant difference between the age-groups in consent to use EES were elderly people had consented more often. Elderly people usually have more drug prescribes than younger and therefore is it more useful for people over 60 years. The risk of interactions increases with the number of drugs.

Background: Pain is one of the most prominent and disturbing symptoms reported by cancer patients. Appropriate pain relief is obtainable in more than 75 % of the patients with optimized analgesic treatment. Opioids and non-opioids are being utilized in cancer pain treatment and analgesics are used to improve the effectiveness of opioids. Gabapentin is primarily used as an anti-epileptic drug that is also recommended as the first-choice drug in treatment of neuropathic pain. Research is being conducted to evaluate cannabinoids as adjuvans analgesics. Sativex is the extract of cannabis sativa plant and is used to treat and ease moderate to severe symptoms of spasticity caused by multiple sclerosis (MS) in Sweden. Several scientific studies have recently studied sativex with positive results and the drug is currently being used in some countries in treatment of resistant cancer-related neuropathic pain. Purpose: The purpose of this paper was to conduct a scientific study and examine whether sativex is as efficient and secure as gabapentin and thus an option as addendum in cancer-related neuropathic pain when the treatment with only opioids is not sufficient for pain relief. Method: This literature study is based on examination of six clinical scientific studies. The articles are searched in PubMed database, the articles are about examination of effectiveness and security of gabapentin and sativex compared to placebo or other equivalent drugs in cancer patients suffering from neuropathic pain. Results: Two of the studies that compared gabapentin with placebo and one that compared Gabapentin with Amitriptylin (an anti depressive drug) showed that gabapentin was an efficient adjuvans analgesic that led to statistically significant pain relief in patients suffering from cancer. The side effects were mild to moderate in all three studies, and overdose of the study-drug was tolerated well. One of three studies evaluating efficacy and safety of sativex showed that the change in daily average pain score during two weeks of treatment was statistically significant in patients in the sativex-group compared to the group of patients receiving THC-extract and placebo-group. In the second study, sativex was compared within three different dosage groups (low, middle and high) as well as placebo and the result showed that sativex had significant pain relief only in patients receiving low dose of sativex. The third study showed that sativex led to pain relief in patients receiving sativex compared to those receiving placebo however the effect was not statistically significant. Dizziness, nausea and vomiting were the most common side effects in all three studies. The side-effects were mild to moderate and no serious safety issues were observed in the first and third studies. In the second study on the other hand, the patients were encouraged to maintain a stable opioid-dose which resulted in more side-effects. Conclusion: All three studies that examined the effectivness of sativex showed improvement on sleeping quality as well as pain relief, where two of the studies showed statistically significant pain relief in patients suffering from neuropathic cancer-pain. Studies on cannabinoids are quite controversial and there are not many global studies available that have studied its safety and efficacy in the treatment of neuropathic cancer-related pain. It is however a growing and upcoming area that is also expected to grow multiply in turnover which should enable more studies being conducted. These results show that sativex has the potential of being a good alternative in the treatment of neuropathic cancer-related pain. Sativex is also effective in low doses without the need for increases over time, furthermore side effects are mild to moderate and possible overdose is well managed by patients. Gabapentin been used in pain management in neuropathic cancer-pain for a long time with minimal side effects. Sativex, on the other hand, is quite new and there are not many studies performed on the medicine. Furthermore, there are no studies comparing sativex and gabapentin which makes it very difficult to conclude whether it holds the same safety and may act as a good alternative to gabapentin. In future studies, sativex should be compared to medicines used today such as gabapentin in order to prove its ability of being an alternative.

The isomers of cyclo(Trp-Pro) (cyclo(L-Trp-L-Pro), cyclo(L-Trp-D-Pro), cyclo(D-Trp-LPro) and cyclo(D-Trp-D-Pro)) have been successfully synthesized and screened for biological activity. High percentage yields were obtained by using the three phase synthesis system, which involves the synthesis of the intermediate protected linear dipeptides, followed by the removal of the protecting Boc groups. This step is followed by cyclization and crystallization of the isomers. The diketopiperazines rings of cyclo(L-Trp-L-Pro) and cyclo(D-Trp-D-Pro) contain cisamide bonds, while cyclo(L-Trp-D-Pro) and cyclo(D-Trp-L-Pro) contain trans-amide bonds. These bonds govern the conformation of the diketopiperazines ring. The isomers have shown different degrees of biological activity, possibly as a result of the orientation of the side chain of tryptophan and this difference in conformation, leading to varying interactions between isomer and a range of receptors. Under experimental conditions, 10-3 M cyclo(L-Trp-D-Pro) and cyclo(D-Trp-L-Pro) showed effective anticancer activity against the cervical cancer cell line, HeLa, resulting in a <50% reduction in cell viability. Cytotoxicity screening with cyclo(D-Trp-L-Pro) indicated that it was hepatocyte-specific in its toxicity, whilst the other isomers were cytotoxic against the other cell types tested. At 1mg/ml, cyclo(L-Trp-L-Pro) proved to be an effective antimicrobial agent against Gram positive bacteria, while cyclo(L-Trp-DPro) effectively inhibited the growth of the Gram negative bacteria, Esherichia coli. Cyclo(D-Trp-L-Pro) proved to be effective against Streptococcus, while cyclo(D-Trp-DPro) effectively reduced viability of the yeast, Candida albicans. Cyclo(D-Trp-L-Pro) was the only isomer to show Ca2+-channel antagonism, whilst the other isomers resulted in opening of the Ca2+-channel. No effects were observed on K+-channel activity for all the isomers tested. The isomers also proved to be valuable antiarrhythmic agents by effectively reducing the time spent in ventricular tachycardia and arrhythmia, as well as decreasing the time for the heart rate to return to a normal sinus rhythm. Furthermore, cyclo(L-Trp-D-Pro) showed positive chronotropic activity, while cyclo(D-Trp-L-Pro) ii showed negative chronotropic activity. In addition, cyclo(L-Trp-D-Pro) and cyclo(D-Trp- L-Pro) also increased the coronary flow rate. 0.125 –1 mM Cyclo(L-Trp-D-Pro) decreased aggregation in washed platelets induced by thrombin. All isomers increased adhesion to an artificial surface when the platelets were stimulated by ADP, yet caused reduced adhesion when the platelets were stimulated by thrombin. These results prove the potential of these compounds as novel agents in a range of biological fields, indicating that a combination of L- and D- amino acids may prove more effective than an agent consisting solely of L-amino acids.