Autism är en neuropsykiatrisk störning som hör till autismspektrumstörning (AST). Vid autism är den sociala kommunikationen och repetitiva sensoriska-motoriska beteenden bristfällig. Autism är 3–4 gånger vanligare hos pojkar än hos flickor. För att diagnostisera autism finns det huvudsakligen två system; DSM- och ICD-systemet. Idag finns ingen godkänd farmakologisk behandling för indikationen autism. Ett ämne som har studerats de senaste åren som potentiell behandling vid autism är oxytocin. Oxytocin är ett neuropeptidhormon som produceras i hypotalamus och brukar benämnas som “lugn och ro-hormonet”. Syftet med denna litteraturöversikt är att undersöka om intranasal oxytocin har någon effekt vid autismsymtomen hos barn 0–19 år. sitet. Ingen av studierna visade signifikant förbättring på det repetitiva beteendet. Ett flertal studier visade en signifikant förbättring i social kommunikation hos patienter som fått intranasal oxytocin, medan andra studier inte tydde på någon signifikant förbättring. Oxytocin förbättrade signifikant förmågan att läsa av känslor från andras ögon utifrån ögonkontakt. Majoriteten av biverkningarna på grund av användning av oxytocin var lindriga.Slutsatsen som dras är att oxytocin kan vara en intressant substans för behandling av autism, åtminstone för social kommunikation. Oxytocin gav biverkningar, majoriteten i form av lindriga biverkningar. Studierna visar olika resultat på förbättring av kommunikation hos autism därmed behövs det ytterligare studier med ett större urval för att kunna stärka resultaten. Även fler studier behövs för att kontrollera om oxytocin kan förbättra repetitiva beteendet eftersom denna litteraturstudie visade motstridiga resultat.

No description available.

Background: Contraceptives for men has existed for centuries. However, the only contraceptives available for men are condoms, withdrawal during sexual intercourse or undergoing Vas occlusion. The issues currently with these methods are that many couples are not comfortable with using condoms and vasectomy is a non-reversible contraceptive as it requires surgery. Currently, only research has been made with regards to hormonal contraceptives for men. The basis for hormonal contraceptives for men is that it disturbs hypothalamic-pituitary–gonadal axis, by suppressing GnRH, LH and FSH in order to suppress spermatogenesis. The substances that have been clinically tested as a potential hormonal contraceptive for men are androgens, androgens together progestins and synthetic androgens. Aim: The aim of this thesis was to examine the effectiveness of the substances that have been used in past and recent clinical trials and the adverse drug reactions/effects. Method: Results from the clinical trials were collected through PubMed with regards to preordained criteria, which resulted in 18 scientific articles being used in the results. Results: Overall, the results showed that the majority of substances used in previous and recent clinical trials are effective in suppressing spermatogenesis. The results also showed that a majority of substances used in previous and recent clinical trials had severe adverse drug effects severe amongst the participants. Discussion and Conclusion:  In summary, the research shows that amongst the substances used in recent and current clinical trials, that synthetic androgens have the best potential as a hormonal contraceptive for men with regards to effectiveness and adverse drug effects.

No description available.

<p>Heavy metals polluting our environment cause concern for developing organisms. Among them, cadmium with extremely slow elimination from the body, causes lower birth weight in humans but has not been classify as a human teratogen. Studies in different laboratory animals have shown that cadmium indeed is a potent teratogen. Exposure to cadmium during early mouse embryonic stages (e.g. day 7-8 post-coitus) interferes with the closure of the anterior neural pore producing exencephalic embryos. The underlying mechanisms are not understood, but the heavy accumulation of cadmium in extra- and intraembryonic endoderm and chorioallantoic placenta, however not in the neuroepithelium, suggests that the effects on neural tube closure is due to indirect mechanisms. In this thesis, the disruption in the mouse embryo at the time of neural tube closure of the hierarchies of some signalling pathways and gene regulatory networks that control embryonic development has been studied after cadmium exposure. Cadmium was shown to cause DNA damage as measured by Comet assay, and to activate genes and proteins in the apoptotic pathways (<i>p53, p21, Bcl-2, Bax</i>, and caspase-3), increasing the number of apoptotic cells mostly in areas of physiological cell death, especially in the neuroepithelium. Many of these effects could be reversed by zinc pre-treatment, known to counteract the teratogenic effect of cadmium. Cadmium was also shown to affect Zn-transport and –regulatory proteins in the embryo, but perhaps more importantly in yolk sac placenta, and in the decidua (ZnT-1, MT-I, and ZIP-4). Using gene arrays, cadmium was found to considerably affect gene expression of rather few genes, such as those of metallothioneins and stress-related proteins, supporting in principle an extraembryonic site of action of cadmium. In addition, a number of genes expressed in the anterior visceral endoderm (<i>Hesx1, HNF3β, Cerl, Otx2</i> and <i>Sox2</i>) where cadmium accumulates, and known to signal to the anterior neuroepithelium, was affected by cadmium. This finding may suggest a new principle for chemical teratogenesis.</p>

Heavy metals polluting our environment cause concern for developing organisms. Among them, cadmium with extremely slow elimination from the body, causes lower birth weight in humans but has not been classify as a human teratogen. Studies in different laboratory animals have shown that cadmium indeed is a potent teratogen. Exposure to cadmium during early mouse embryonic stages (e.g. day 7-8 post-coitus) interferes with the closure of the anterior neural pore producing exencephalic embryos. The underlying mechanisms are not understood, but the heavy accumulation of cadmium in extra- and intraembryonic endoderm and chorioallantoic placenta, however not in the neuroepithelium, suggests that the effects on neural tube closure is due to indirect mechanisms. In this thesis, the disruption in the mouse embryo at the time of neural tube closure of the hierarchies of some signalling pathways and gene regulatory networks that control embryonic development has been studied after cadmium exposure. Cadmium was shown to cause DNA damage as measured by Comet assay, and to activate genes and proteins in the apoptotic pathways (p53, p21, Bcl-2, Bax, and caspase-3), increasing the number of apoptotic cells mostly in areas of physiological cell death, especially in the neuroepithelium. Many of these effects could be reversed by zinc pre-treatment, known to counteract the teratogenic effect of cadmium. Cadmium was also shown to affect Zn-transport and –regulatory proteins in the embryo, but perhaps more importantly in yolk sac placenta, and in the decidua (ZnT-1, MT-I, and ZIP-4). Using gene arrays, cadmium was found to considerably affect gene expression of rather few genes, such as those of metallothioneins and stress-related proteins, supporting in principle an extraembryonic site of action of cadmium. In addition, a number of genes expressed in the anterior visceral endoderm (Hesx1, HNF3β, Cerl, Otx2 and Sox2) where cadmium accumulates, and known to signal to the anterior neuroepithelium, was affected by cadmium. This finding may suggest a new principle for chemical teratogenesis.

<p>The aryl hydrocarbon receptor (Ah-receptor) is a member of the bHLH-PAS protein family. The Ah-receptor is a ligand dependent transcription factor, which activates a wide range of genes, most notably the xenobiotica metabolising genes, CYP1A1 and CYP1A2. The biological function of the Ah-receptor is still unknown and an endogenous ligand has yet not been identified. A possible Ah-receptor ligand is 6-formylindolo[3,2-b]carbazole (FICZ). FICZ has a high affinity for the Ah-receptor and is rapidly metabolised by CYP1A1, CYP1A2 and aldehydeoxidase (AOX). To try to trap FICZ or other possible endogenous Ah-receptor ligands, the metabolising enzymes CYP1A1, CYP1A2 and AOX were blocked. This was achieved through chemical blockage of CYP1A1 and CYP1A2 by ellepticin and through silencing with siRNA directed against CYP1A1 and CYP1A2. Successful blockage would be seen as an increase in Ah-receptor dependent XRE-luciferase activity. Chemical blockage of AOX with tungstate did not affect FICZ-dependent XRE-luciferase activation which could indicate that HepG2 cells lack AOX. The chemical blockage of CYP1A1 and CYP1A2 with ellepticin modified the XRE-luciferase response, but did not completely block Ah-receptor activation. In addition it is possible that ellepticin is a ligand for the Ah-receptor. The blockage of CYP1A1 by siRNA was successful; a silencing of CYP1A1 mRNA by at least 50 percent was detected. However due to lack of time it was not tested if the blockage of CYP1A1 and CYP1A2 was sufficient to trap Ah-receptor ligands.</p>

Bakgrund: Alzheimers sjukdom (AD) är neurodegenerativ och kännetecknas framför allt av det tidiga symtomet minnesförlust. De patologiska skadorna i hjärnan utmärks av senila plack och neurofibrillära nystan (NFTs). Senila plack består av peptiden amyloid-b (Ab) och NFTs innehåller proteinet tau. Ab har länge stått i fokus när det kommer till patogenesen vid AD och forskning kring behandlingsstrategier mot sjukdomen har länge riktat sig mot denna peptid, men än så länge utan lyckade resultat. Mer fokus har riktats till tau och i nuläget finns det ett antal tau-riktade behandlingsstrategier under utveckling och tau-immunoterapi är en av dessa. Syfte: Idag finns det inte någon behandling som botar AD vilket betyder att det är viktigt att hitta nya behandlingsstrategier mot sjukdomen. Tidigare studier tyder på att tau är ett potentiellt mål för behandling mot AD och syftet med detta arbete var därför att undersöka om tau-immunoterapi är en möjlig behandlingsstrategi vid AD. Metod: Sekundärdata samlades in från databasen PubMed. Datan granskades och bedömdes som användbar eller inte. Detta resulterade i att sju orginalartiklar valdes till arbetet, sex studier i djurmodeller och en klinisk studie.  Resultat: Studierna i djurmodellerna visade att tau-immunoterapi reducerade patologiskt tau och i hälften av studierna observerades även en förbättring av de kliniska symtomen. Den kliniska studien visade att AADvac1 är säkert och ansågs vara en lovande kandidat för vidare studier. Slutsats: Resultaten från studierna visar att tau-immunoterapi är en lovande behandlingsstrategi vid AD. Trots detta krävs det fler kliniska studier som undersöker tau-immunoterapi för att säkerställa om behandlingen har någon klinisk effekt på patienter med AD eller inte.

Background: Statins are among the most used drugs in Sweden. There are currently four statins available on the Swedish market; atorvastatin, simvastatin, pravastatin and rosuvastatin. Statins act by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme-A reductase, also known as HMG-CoA-reductase. HMG-CoA-reductase is the rate-limiting enzyme of the cholesterol synthesis. Decreased hepatic cholesterol leads to increased low-density lipoprotein (LDL) clearance from plasma to liver cells. Having a high level of LDL cholesterol is potentially dangerous as it can lead to atherosclerosis and cardiovascular disease. Statins significantly reduce cardiovascular morbidity and mortality in patients with and without coronary heart disease. Purpose: The aim of this work was to investigate if there are any differences between the different statins according to contemporary evidence. Method: This is a literary analysis. Studies included were searched from PubMed. A total of five studies were included. Results: The result of this study indicates rosuvastatin to be most efficacious in lowering LDL cholesterol (LDL-C), triglycerides and total cholesterol. It also improved the high-density lipoprotein cholesterol (HDL-C) better than atorvastatin, simvastatin and pravastatin. Study 1 showed rosuvastatin to lower LDL-C with statistical significance (P&lt;0.001) across dose ranges (10-40 mg) after 12 weeks. Study 2 compared a dose ratio of 1:2 between rosuvastatin and simvastatin in lowering LDL-C with a 3.24% (95% CI 4.10 to 2.38) favor of rosuvastatin. Study 4 compared effects of atorvastatin 80 mg and rosuvastatin 20 mg in patients with ST elevation myocardial infarction in a 4-week therapy. Rosuvastatin 20 resulted in a 35% compared with atorvastatin 80 mg 34% (P=0.59) reduction in LDL-C levels. Study 1 demonstrated rosuvastatin to improve HDL-C levels in daily doses of 40 mg with statistical significance compared with atorvastatin, simvastatin and pravastatin. Study 1 demonstrated rosuvastatin to lower total cholesterol with statistical significance (P&lt;0.002) across doses compared with atorvastatin, simvastatin and pravastatin. Study 1 also demonstrated rosuvastatin to lower triglycerides more. In daily doses of 40 mg rosuvastatin had a statistical significance (P&lt;0.002) versus simvastatin and pravastatin, but not atorvastatin. The P value between rosuvastatin and atorvastatin was not mentioned, neither the P-value between atorvastatin, simvastatin and pravastatin. Conclusion: Statins are not equipotent. Rosuvastatin showed greater results in reducing LDL-C, triglycerides and total cholesterol with no increased risk of adverse events compared with atorvastatin, simvastatin and pravastatin. Rosuvastatin still lacks in clinical experience which makes needs for further studies on this topic.

Metals have been used by humans for thousands of years, and this has resulted in increased concentrations in the biosphere. The environment around point-sources, such as mines and smelters, are of particular concern, as metals may accumulate to high concentrations, and potentially reach levels toxic to the local flora and fauna. This thesis focuses on the effects on pied flycatcher populations of two such point-sources, a lead mine and enrichment plant, and a sulfide ore smelter. Mining activities at the lead mine ceased in 2001 and pied flycatcher populations were assessed before and after the closure. At the sulfide ore smelter, pied flycatchers were studied during the 1980s. Since then, the metal emissions to air from the smelter (e.g. arsenic, cadmium, copper, mercury, lead and zinc) have been greatly reduced (by 93 – 99%). Pied flycatchers from these two contaminated environments differed in their responses to reduced atmospheric deposition. At the mine site, nestling responses reflected the reduced atmospheric deposition and less lead accumulated in their tissues. However, lead levels were still high enough to cause negative effects on blood status (δ-aminolevulinic acid dehydratase [ALAD], hemoglobin [Hb], hematocrit [ht], and mean cell hemoglobin concentration) and reproduction (reduced clutch size, increased mortality and reduced breeding success), as was observed when the mine was in operation. Along the pollution gradient away from the smelter, nestling concentrations reflected the metal load in the soil pool, accumulating over time, rather than the atmospheric deposition. This resulted in only a minor response to decreased metal deposition (slightly reduced liver lead concentrations at 3.5 – 90 km from the smelter). This suggests that in environments with highly polluted soils, decreased inputs of atmospheric metal deposition have only minor impacts, and recovery from contamination should not be expected within decades. The high metal concentrations in the vicinity of the smelter contributed to poorer blood status (ALAD, Hb and ht), induced oxidative damage and defenses, and decreased reproduction (increased mortality and reduced breeding success). There were only minor improvements in blood and reproductive variables at 3.5 km from the smelter. / Metaller är grundämnen som inte kan bildas eller förstöras av människan. De förekommer i mineraler i berggrunden och finns överallt på jorden. Människans användning av metaller har dock medfört att de återfinns i högre halter i miljön än de annars skulle gjort. Trots att metallerna kan spridas och transporteras långa sträckor med luftmassorna, är det främst kring källorna, såsom metallindustrier, man kan hitta metaller i tillräckligt höga halter för att orsaka skada på växter och djur. I denna avhandling presenteras undersökningar av hur svartvit flugsnappare (Ficedula hypoleuca) påverkas kring två metallindustrier i norra Sverige. Det ena är en numera nedlagd blygruva med anrikningsverk i Laisvall, där vi studerade populationer av svartvit flugsnappare före och efter att industrin stängdes. Det andra är smältverket Rönnskärsverken, utanför Skelleftehamn, som varit i drift sedan 1930-talet. I föroreningsgradienten från smältverket studerades effekter av 20 års kraftigt minskade metallutsläpp till luften som följd av förbättrade reningstekniker. Resultaten kring industrierna visar att fåglarna svarade olika på de minskade metallutsläppen. Kring blygruvan minskade halterna av bly i flugsnapparungar med samma takt som nedfallen (mätt i mossa) och bytesdjuren (myror). Däremot, kring smältverket, var fåglarna fortfarande exponerade för höga halter av de giftiga ämnena arsenik, kadmium, kvicksilver och bly, på i princip samma nivåer som 20 år tidigare, trots att utsläppen minskat med 93 – 98%. Orsaken till detta tros vara skillnader på föroreningsgraden i markens översta lager, mårskiktet. Vi kunde visa att flugsnapparna kring smältverket främst fick i sig metallerna från marken, som efter flera årtionden med utsläpp från industrin innehöll mycket höga metallhalter. Detta kan förklara att fåglarna trots att utsläppen var låga, fortfarande var utsatta för stor metallexponering. Det snabba svaret på minskad metallspridning (bly och zink) som flugsnapparna vid blygruvan visade, antar vi berodde på att mindre mäng metaller fanns i marken. Trots minskningen var metallhalterna i fåglarna vid gruvområdet fortfarande tillräckligt höga för att, liksom vid smältverket, påverka fåglarnas hälsa. De uppvisade bl.a. låga blodvärden och tecken på oxidativ stress. Vidare var ungdödligheten förhöjd, vilket ledde till lägre häckningsframgång. Slutsatsen är att markens innehåll av metaller har stor betydelse för återhämtningsförloppet för svartvit flugsnappare efter minskat metallnedfall, och att en relativt snabb återhämtning kan förväntas i områden med något lägre metallhalter i mårskiktet, medan återhämtning i områden där marken är kraftigt förorenad inte kan förväntas förrän efter flera årtionden, även om nedfallet upphört nästan helt.