Metformin in gestational diabetes mellitus

METFORMIININ KÄYTTÖ RASKAUSDIABETEKSESSA Raskausdiabeteksella tarkoitetaan sokeriaineenvaihdunnan häiriötä, joka todetaan ensimmäisen kerran raskauden aikana. Hoidolla voidaan vähentää raskausdiabetekseen liittyviä äidin ja vastasyntyneen haittoja. Lääkitystä tarvitaan, jos ruokavaliohoidolla ei saavuteta hyvää sokeritasapainoa. Perinteisesti lääkityksenä on käytetty insuliinia, mutta metformii¬nin käyttöä insuliinin vaihtoehtona on ehdotettu. Metformiini läpäisee istukan, mutta sen läpäisymekanismi ei ole selvillä. Tämän tutkimuskokonaisuuden pääasiallisin tarkoitus oli verrata metformiinin tehokkuutta ja turvallisuutta insuliiniin raskausdiabeteksen hoidossa selvittämällä lääkkeen vaiku¬tusta äitiin ja vastasyntyneeseen. Lisäksi haluttiin tutkia, mitkä tekijät ennustavat insulii¬nin tarvetta metformiinin lisänä, jotta saavutettaisiin hyvä sokeritasapaino. Metformiinin annoksen vaikutus äitiin ja vastasyntyneeseen arvioitiin mittaamalla metformiinin pitoisuus äidistä, ja sikiön puolelta napanuoran veressä. Tässä tutkimuksessa selvitettiin myös aktiivisen kuljetusproteiinin (OCT) merkitystä metformiinin kulkeutumiseen istukan läpi perfusiomalla istukkaa ex vivo . Ex vivo istukkaperfuusiotutkimuksen tulokset viittasivat siihen, että OCT-kuljetusproteiinilla ei ollut todennäköisesti merkittävää osuutta metformiinin kulkeutumisessa istukan läpi. Metformiinin pitoisuusmittaukset synnytyksen yhteydessä osoittivat metformiinin siirtyvän sikiöön istukan läpi suuressa määrin (96 %) kertymättä kuitenkaan sikiön verenkiertoon. Metformiinin pitoisuudella ei ollut vaikutusta vastasyntyneen hyvinvointiin. Maksi¬maalisella metformiinin annostuksella ja korkealla metformiinipitoisuudella todettiin olevan suotuisa vaikutus äidin painon nousuun raskauden aikana. Insuliiniin verrattuna metformiini ei lisännyt äidin, sikiön tai vastasyntyneen haittatapahtumia, eikä sillä ollut vaikutusta synnytystapaan. Sokeritasapaino insuliini- ja metformiinilääkityksen aikana oli yhtäläinen arvioitaessa sitä HbA1c- ja fruktosamiinimittauksilla, mutta 21 % metformiinin käyttäjistä tarvitsi lisäksi insuliinia hyvän sokeritasapainon saavuttamiseksi. Tutkimuksesssa todettiin, että mitä iäkkäämpi äiti oli, mitä varhaisemmassa raskauden vaiheessa sokerirasitus oli tehty ja lääkitys aloitettu, ja mitä korkeammat HbA1c ja fruktosamiinipitoisuudet olivat, sitä suuremmalla todennäköisyydellä metformiinin lisänä tarvittiin insuliinia.

Optimization of the procedure for removing iron deposits on ceramic filter media

In this thesis, cleaning of ceramic filter media was studied. Mechanisms of fouling and dissolution of iron compounds, as well as methods for cleaning ceramic membranes fouled by iron deposits were studied in the literature part. Cleaning agents and different methods were closer examined in the experimental part of the thesis. Pyrite is found in the geologic strata. It is oxidized to form ferrous ions Fe(II) and ferric ions Fe(III). Fe(III) is further oxidized in the hydrolysis to form ferric hydroxide. Hematite and goethite, for instance, are naturally occurring iron oxidesand hydroxides. In contact with filter media, they can cause severe fouling, which common cleaning techniques competent enough to remove. Mechanisms for the dissolution of iron oxides include the ligand-promoted pathway and the proton-promoted pathway. The dissolution can also be reductive or non-reductive. The most efficient mechanism is the ligand-promoted reductive mechanism that comprises two stages: the induction period and the autocatalytic dissolution.Reducing agents(such as hydroquinone and hydroxylamine hydrochloride), chelating agents (such as EDTA) and organic acids are used for the removal of iron compounds. Oxalic acid is the most effective known cleaning agent for iron deposits. Since formulations are often more effective than organic acids, reducing agents or chelating agents alone, the citrate¿bicarbonate¿dithionite system among others is well studied in the literature. The cleaning is also enhanced with ultrasound and backpulsing.In the experimental part, oxalic acid and nitric acid were studied alone andin combinations. Also citric acid and ascorbic acid among other chemicals were tested. Soaking experiments, experiments with ultrasound and experiments for alternative methods to apply the cleaning solution on the filter samples were carried out. Permeability and ISO Brightness measurements were performed to examine the influence of the cleaning methods on the samples. Inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis of the solutions was carried out to determine the dissolved metals.

Detection of Illicit Drugs and Drug Precursors with Cantilever-Enhanced Photoacoustic Spectroscopy

In this study, cantilever-enhanced photoacoustic spectroscopy (CEPAS) was applied in different drug detection schemes. The study was divided into two different applications: trace detection of vaporized drugs and drug precursors in the gas-phase, and detection of cocaine abuse in hair. The main focus, however, was the study of hair samples. In the gas-phase, methyl benzoate, a hydrolysis product of cocaine hydrochloride, and benzyl methyl ketone (BMK), a precursor of amphetamine and methamphetamine were investigated. In the solid-phase, hair samples from cocaine overdose patients were measured and compared to a drug-free reference group. As hair consists mostly of long fibrous proteins generally called keratin, proteins from fingernails and saliva were also studied for comparison. Different measurement setups were applied in this study. Gas measurements were carried out using quantum cascade lasers (QLC) as a source in the photoacoustic detection. Also, an external cavity (EC) design was used for a broader tuning range. Detection limits of 3.4 particles per billion (ppb) for methyl benzoate and 26 ppb for BMK in 0.9 s were achieved with the EC-QCL PAS setup. The achieved detection limits are sufficient for realistic drug detection applications. The measurements from drug overdose patients were carried out using Fourier transform infrared (FTIR) PAS. The drug-containing hair samples and drug-free samples were both measured with the FTIR-PAS setup, and the measured spectra were analyzed statistically with principal component analysis (PCA). The two groups were separated by their spectra with PCA and proper spectral pre-processing. To improve the method, ECQCL measurements of the hair samples, and studies using photoacoustic microsampling techniques, were performed. High quality, high-resolution spectra with a broad tuning range were recorded from a single hair fiber. This broad tuning range of an EC-QCL has not previously been used in the photoacoustic spectroscopy of solids. However, no drug detection studies were performed with the EC-QCL solid-phase setup.

Starting Insulin Treatment in Type 2 Diabetes

Type 2 diabetes is a disorder of glucose metabolism characterized by chronic hyperglycemia. Initially type 2 diabetes is characterized by insulin resistance and impaired function of beta cells, leading progressively to insulin deficiency. Type 2 diabetes is treated with diet and other lifestyle changes, and with medication modulating e.g. insulin resistance, liver glucose production and insulin secretion. Injectable insulin is added to the treatment when lifestyle changes and other medication are insufficient to maintain adequate control of hyperglycemia. The aim of the treatment is to remove the symptoms of diabetes and to prevent late complications of diabetes. Insulin was traditionally started at hospital wards, but from the early 1990’s also in outpatient care. The first substudy of this thesis examined retrospectively initiation practices and how successfully insulin treatment was introduced in 1990 – 1996 in Southwestern Finland. This study aimed also at identifying the best methods of controlling plasma glucose. It showed that in the 1990’s the incidence of insulin treatment increased and was initiated more often in outpatient care than previously. The use of combination treatment also increased, first with sulfonylureas and later with metformin as the oral drug. In combination therapy the insulin dose was smaller than with insulin monotherapy. HbA1c improved similarly in middle-aged and older age groups. Weight increase associated with insulin initiation was smaller when combined with oral agents. A prospective insulin initiation study (1994 – 1998) tested the hypothesis that hyperglycemia (fasting and postprandial hyperglycemia) may affect the outcome of insulin initiation. The type of hyperglycemia was determined by the relation of fasting plasma glucose to HbA1c. Treatment was initiated with insulin Lente or human NPH insulin. In patients treated with insulin monotherapy twice daily the decline in HbA1c was markedly greater for postprandial than fasting hyperglycemia patients suggesting that hyperglycemia type has significance in the selection of the insulin regimen. Another insulin initiation study showed that patients with fasting hyperglycemia starting on insulin (2004-2005) were significantly more prone to overweight than patients with postprandial hyperglycemia. Irrespective of the insulin preparation (insulin NPH or insulin glargine), patients with fasting hyperglycemia had a greater weight increase compared to patients with postprandial hyperglycemia. Special attention should be paid to prevention of weight increase in these patients.