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Biomedical subjects

M Niemi

Publications and source records attributed to M Niemi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Rifampin decreases the plasma concentrations and effects of repaglinide.

OBJECTIVE: To study the effects of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of repaglinide, a new short-acting antidiabetic drug. METHODS: In a randomized, two-phase crossover study, nine healthy volunteers were given a 5-day pretreatment with 600 mg rifampin or matched placebo once daily. On day 6 a single 0.5-mg dose of repaglinide was administered. Plasma repaglinide and blood glucose concentrations were measured up to 7 hours. RESULTS: Rifampin decreased the total area under the concentration-time curve of repaglinide by 57% (P < .001) and the peak plasma repaglinide concentration by 41% (P = .001). The elimination half-life of repaglinide was shortened from 1.5 to 1.1 hours (P < .01). The blood glucose decremental area under the concentration-time curve from 0 to 3 hours was reduced from 0.94 to -0.23 mmol/L x h (P < .05), and the maximum decrease in blood glucose concentration from 1.6 to 1.0 mmol/L (P < .05) by rifampin. CONCLUSIONS: Rifampin considerably decreases the plasma concentrations of repaglinide and also reduces its effects. This interaction is probably caused by induction of the CYP3A4-mediated metabolism of repaglinide. It is probable that the effects of repaglinide are decreased during treatment with rifampin or other potent inducers of CYP3A4, such as carbamazepine, phenytoin, or St John's wort.

Adult↗
PubMed1999

Heparan sulphate and HB-GAM (heparin-binding growth-associated molecule) in the development of the thalamocortical pathway of rat brain.

Extracellular matrix (ECM) molecules, such as laminin, tenascin, chondroitin sulphate proteoglycans and heparan sulphate proteoglycans have been suggested to have 'signpost' and directing roles in the formation of axonal projections in cortical development. We show here that the expression of the neurite outgrowth-promoting protein heparin-binding growth-associated molecule (HB-GAM) and N-syndecan, a transmembrane heparan sulphate proteoglycan previously isolated as a receptor for HB-GAM, is spatiotemporally associated with the developing thalamocortical pathway in the rat brain. Using in situ hybridization, thalamic neurons were shown to express mRNA for N-syndecan, and in vitro, thalamic neurons grew more neurites on HB-GAM than on laminin. The HB-GAM-induced neurite outgrowth in thalamic neurons was inhibited by heparitinase, heparin, soluble N-syndecan and by an excess of soluble HB-GAM in the culture medium. In a pathway assay, thalamic neurons selectively preferred attaching and growing neurites on matrices containing HB-GAM than on those containing fibronectin or laminin alone, suggesting that HB-GAM may modulate the effect of other ECM proteins. On an unfixed brain slice preparation, thalamic neurons repeatedly showed a typical neurite outgrowth and attachment pattern resembling the expression pattern of HB-GAM. On the brain slices, the neurite outgrowth was significantly inhibited by heparitinase, heparin and soluble HB-GAM, thus displaying features of neurite outgrowth on matrix-bound HB-GAM. Our results suggest that HB-GAM is important for the neurite outgrowth of thalamic neurons and it may function as an ECM-bound guidance cue for thalamic neurons that possess HB-GAM-binding heparan sulphates on their cell membrane.

Animals↗
PubMed1999

Functional genomics and DNA array techniques in atherosclerosis research.

DNA arrays are revolutionizing the analysis of gene expression and single nucleotide polymorphisms of genomic DNA. Currently, the expression of 10-15% of human genes can be analysed simultaneously in a single experiment using cDNA or oligonucleotide-based format of DNA array. Alternatively, smaller DNA arrays with a limited number of selected genes, such as cytokines, growth factors or transcription factors, can be used. In concordance with Human Genome Project, after a few years, the DNA arrays will allow the analysis of expression of the whole human genome and will have a great impact on basic research, drug development and diagnostics. It is important to characterise mechanisms of atherosclerosis-related diseases at the level of gene expression so that new therapeutic strategies can be identified. With the aid of DNA array it is possible to identify multiple, simultaneous, transcriptional events that ameliorate or contribute to atherogenesis. The results are non-physical maps of the function, hierarchy and interactions of genetic programs. In this review we focus on DNA array technology and its applications in atherosclerosis research.

Arteriosclerosis↗
PubMed1999

The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects.

BACKGROUND: The polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD). AIMS: To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD. METHODS: Apolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography. RESULTS: In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0. 28 (95% confidence interval 0.08-0.92). There was no protective effect in men. The relative risk for GSD was 1.2 (0.8-1.7) for hypertensive women and 1.8 (1.0-2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men. CONCLUSIONS: The data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD.

Adult↗
PubMed1996

Is the development of adenoma and carcinoma in proximal colon related to apolipoprotein E phenotype?

BACKGROUND & AIMS: Alterations in plasma lipoprotein levels and bile acid metabolism observed in patients with colorectal adenoma and carcinoma may reflect a genetic background predisposing to altered lipid metabolism and tumors. This study was designed to determine whether the polymorphism of apolipoprotein E, one of the key regulatory proteins in cholesterol metabolism, is associated with proximal or distal colonic neoplasia. METHODS: Apolipoprotein E phenotype was determined in 135 patients with colorectal adenoma, 122 patients with colorectal carcinoma, and 199 randomly selected control subjects. RESULTS: The frequency of the epsilon 4 allele of apolipoprotein E was low (0.075 and 0.073) in patients with proximal adenoma and those with carcinoma, respectively, compared with the control subjects (0.181) (P < 0.05). In patients with distal tumors, there was no alteration in epsilon 4 frequency. In all subjects with the epsilon 4 allele compared with subjects without epsilon 4, the odds ratio for proximal adenoma was 0.36 (95% confidence interval, 0.14-0.89), and the odds ratio for proximal carcinoma was 0.35 (95% confidence interval, 0.14-0.86). CONCLUSIONS: The data suggest that the epsilon 4 allele of apolipoprotein E provides protection from the development of adenoma and carcinoma of the proximal colon. These results support the theory that there are common susceptibility genes modulating the susceptibility to external carcinogenic factors.

Adenoma↗
PubMed1996

High and unchanged sperm counts of Finnish men.

Several recent reports have suggested that the sperm counts of normal men are declining in most countries. In this study the sperm counts of Finnish men, and their possible changes during the past 28 years, were investigated. The material consisted of semen samples from 238 normal healthy men of unknown fertility and 5481 men from infertile couples. The means (medians) of semen volume, sperm density and total sperm count in normal men were 3.3 (3.0) ml, 133.9 (94.0) x 10(6)/ml and 396.6 (309.0) x 10(6), respectively. These parameters and the relative frequency distribution of the sperm density were similar to those reported elsewhere in the 1940s. Multiple linear regression analysis revealed a significant decrease in semen volume, whereas sperm density and total sperm count of infertile men had not changed significantly during the past 28 years. In addition, no change in sperm counts was associated with the year of men's birth.

Adult↗
PubMed1994

Detection of retinopathy by non-mydriatic fundus photography in diabetics treated with oral hypoglycaemic agents or diet.

OBJECTIVE: To determine the prevalence of retinopathy by non-mydriatic fundus photography in diabetics treated with oral hypoglycaemic agents or diet. DESIGN: Cross-sectional survey of diabetes-induced fundal changes assessed by fundus photography. SETTING: Area of Health Centre of Oulu. Population 100,000. SUBJECTS: All 1,228 diabetic patients, aged 30 years or over and treated with oral hypoglycaemic agents or diet at the Health Centre of Oulu. MAIN OUTCOME MEASURES: Presence and severity of diabetic retinopathy in fundus photographs, need for laser photocoagulation, age, hypertension, body mass index (BMI), duration of diabetes, type of treatment of diabetes. RESULTS: Retinopathy was observed in 178 (18%) of those 1,015 diabetics examined at the health centre. Retinopathic changes requiring laser treatment were observed in 15 cases, and eight of them had not been diagnosed earlier. Sixty non-attenders photographed at the Central University Hospital were also included, and 12 of them had retinopathy. The presence of retinopathy was associated with long duration of diabetes, poor glycaemic control, and high systolic blood pressure. No association was detected with sex, age at onset of diabetes, BMI, medication for coronary artery disease, or hypertension. CONCLUSIONS: Non-mydriatic fundus photography detected a high prevalence of retinopathy in diabetic patients. Half of those with preproliferative changes were previously undiagnosed cases, and five were in need of immediate laser treatment. It is concluded that fundus photography is a useful tool for detecting retinopathy in a primary health care setting.

Adult↗