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H K Kulmala

Publications and source records attributed to H K Kulmala.

10 recordsLinked to original sources
PubMed1992

Pharmacokinetics of teicoplanin upon multiple dose intravenous administration to normal healthy male volunteers.

Teicoplanin pharmacokinetics were investigated upon multiple dose intravenous administration of 6 and 12 mg kg-1 in 10 normal, healthy, male volunteers, using a two-period, randomized, crossover design; six subjects completed both periods. On day 1, 6 or 12 mg kg-1 was administered every 12 h as a 30-min constant rate intravenous infusion (two doses). Starting on day 2, the same dose (6 or 12 mg kg-1) was administered every 24 h for an additional 13 days. Blood and urine samples were collected over 21 days. Serum and urine were analyzed using a microbiological assay. Following a minimum of 3 weeks after completion of the first period, subjects were crossed over to the other dose. Following multiple dose intravenous administration of 6 and 12 mg kg-1, median pharmacokinetic parameters included: steady-state volume of distribution of 1.4 and 1.2 l kg-1; total clearance of 12.2 and 14.0 ml h-1 kg-1; renal clearance of 11.1 and 10.3 ml h-1 kg-1; and terminal disposition half-life of 159 and 155 h, respectively. No statistically significant dose-related difference was observed. In addition, a cross-study comparison further supports dose proportionality of teicoplanin upon multiple dose intravenous administration of 3 to 12 mg kg-1.

Adult↗
PubMed1992

Applicability of teicoplanin dosage adjustment guidelines for renally impaired patients over the range of 3 to 30 mg kg-1.

The pharmacokinetics of teicoplanin were investigated in 13 subjects with various degrees of renal impairment using a randomized two-period crossover design; 11 subjects completed both periods. Doses of 3 and 30 mg kg-1 were administered as single dose, 60-min constant rate intravenous infusions. Blood samples were obtained over 28 days and urine was collected over 48 h. Serum and urine were analyzed using a microbiological assay. As previously observed in studies conducted in renally impaired subjects, teicoplanin total and renal clearance significantly decreased with decreasing creatinine clearance (p < 0.0001). However, for these parameters, no differences between doses were observed. Dosage adjustment guidelines for renally impaired patients are usually developed using the ratio of total clearance in renally impaired patients to the total clearance in patients with normal renal function. Since no dose-related differences existed in the relationship between teicoplanin total clearance and creatinine clearance, initial dosage adjustment guidelines for renally impaired patients developed at 3 or 30 mg kg-1 are applicable over the range of 3 to 30 mg kg-1.

Aged↗
PubMed1992

Pharmacokinetics of teicoplanin upon multiple-dose intravenous administration of 3, 12, and 30 milligrams per kilogram of body weight to healthy male volunteers.

Teicoplanin pharmacokinetics were evaluated after multiple-dose intravenous administration to healthy male volunteers by using a randomized, double-blind, parallel design. Doses of 3, 12, or 30 mg of teicoplanin per kg of body weight were administered every 24 h for 14 days as 60-min constant-rate intravenous infusions. Blood and urine samples were collected over 21 days and analyzed by a microbiological assay. Twenty-three subjects were included in the pharmacokinetic analysis. The median pharmacokinetic parameters upon multiple-dose intravenous administration of 3, 12, and 30 mg/kg included steady-state volumes of distribution of 0.94, 0.77, and 0.68 liter/kg; total clearances of 11.9, 12.0, and 13.2 ml/h/kg; and terminal disposition half-lives of 143, 166, and 96 h, respectively. Renal clearance accounted for approximately 95% of total clearance. No dose-related differences existed for teicoplanin total or renal clearance. The steady-state volume of distribution decreased significantly with increasing doses. As a result of the decrease in the volume of distribution, the terminal disposition half-life at 30 mg/kg was significantly decreased. However, the decreases in the volume of distribution and terminal disposition half-life are of limited clinical importance, since steady-state trough concentrations in serum increase in proportion to dose. Combined results of all multiple-dose studies with similar durations of sample collection indicate no dose-related differences for any pharmacokinetic parameters from 3 to 12 mg/kg. As observed in the present study, no dose-related differences exist for teicoplanin total and renal clearances from 3 to 30 mg/kg. However, at 30 mg/kg, a significant decrease in the steady-state volume of distribution is observed. As a consequence of the reduction in the volume of distribution at 30 mg/kg with no change in clearance, the terminal disposition half-life is decreased.

Adult↗
PubMed1987

Behavioral suppression following 3,4-methylenenedioxymethamphetamine.

Rotation in rats was employed as an assay of the central dopaminergic activity of 3,4-methylenedioxymethamphetamine (MDMA). This agent was observed to possess predominantly amphetamine-like actions at low doses. However, at higher doses it also appears to stimulate the dopamine receptor directly. Following a third dose of MDMA, a significant decrease in rotation was evident to this drug and to amphetamine, suggesting a neurotoxic or long-term suppressive action of MDMA.

3,4-Methylenedioxyamphetamine↗
PubMed1987

A novel, adaptable and inexpensive computerized activity meter.

A number of activity meters ranging from fully manual to fully automated have been described. A computerized activity meter, used primarily as a rotational activity chamber, is described. This inexpensive system is built around a Commodore 64 computer interfaced through a circuit board to the meters. Each computer can run four chambers and, as a rotometer, can distinguish quarter and full turns in either direction. The system is easily adapted to record data from various behavioral chambers, including an open field with photocell beams.

Animals↗
PubMed1985

Some enkephalin- or VIP-immunoreactive hippocampal pyramidal cells contain neurofibrillary tangles in the brains of aged humans and persons with Alzheimer's disease.

Neurofibrillary tangles are one of the histopathological neuronal abnormalities present in normal aging and especially in Alzheimer's Disease. We have utilized immunocytochemical staining for neuropeptides followed by Congo red with gallocyanin counterstaining and polarized illumination to determine whether enkephalin (Enk), somatostatin (Som), cholecystokinin (CCK), or vasoactive intestinal polypeptide (VIP) are contained in neurons afflicted with such tangles. A few Enk- or VIP-immunoreactive pyramidal cells in field hl and subiculum were found to contain tangles. Many such Enk- or VIP-immunoreactive neurons and cells containing Som- or CCK-like immunoreactivity did not contain such tangles.

Adult↗
PubMed1985

Role of the senile plaque in neuropeptide deficits of Alzheimer's disease.

Senile plaques participate in a cropping of the dendritic tree of enkephalinergic dentate granule cells and hl and subicular pyramidal cells. Somatostatin-containing pyramidal neurons are lost in Alzheimer's disease, whereas nonpyramidal somatostatin neurons are less affected. Fibers containing somatostatin penetrate immature, but not end-stage senile plaques. The senile plaque may precipitate much of the hippocampal denervation seen in Alzheimer's disease.

Alzheimer Disease↗
PubMedDate not supplied

Brain reactive antibodies and the blood-brain barrier: observations in aging rodents and the effects of peripheral kainic acid.

This study was initiated to confirm the existence of brain-reactive autoantibodies and to determine if such antibodies have higher affinity for brain regions especially affected in Alzheimer's disease. Serum collected from 90, 300, and 600 day old mice was incubated against brain tissues from these same mice, followed by incubation with fluorescently tagged rabbit antimouse IgG. No antibodies were present in the youngest serum, but considerable antibodies were present at 300 and, especially, at 600 days. Such antibodies were present in the blood vessels, but not in the brains of older animals. These antibodies, applied exogenously, labeled cells equally in all three ages of brains including most cortical and many other neurons, indicating that they are not neurotransmitter specific. In a further study, kainic acid or saline was administered peripherally to 15-month old rats. Kainic acid damaged the blood brain barrier and allowed the CNS entry of brain-reactive antibodies, especially into the subregions of hippocampus most damaged in Alzheimer's.

Aging↗
PubMedDate not supplied

Immunocytochemical localization of enkephalin-like immunoreactivity in neurons of human hippocampal formation: effects of ageing and Alzheimer's disease.

The localization of neurons containing enkephalin-like immunoreactivity was studied within the human hippocampal formation. It was present in numerous dentate granule cells and a few larger neurons within the dentate molecular layer. In hippocampus proper, numerous pyramidal cells also demonstrated it, especially in field H1 of Rose (1926) and subiculum. No difference attributable to ageing or to dementia of the Alzheimer type was seen in this distribution. Post-mortem delay was the major factor affecting the intensity of its immunocytochemical localization to hippocampal cells and nonspecific background staining, due to binding of the secondary antiserum, increased directly with this. Some dendrites of dentate granule cells with immunoreactivity were found entering senile (neuritic) plaques in tissue from cases of Alzheimer's disease. These dendrites appeared morphologically normal.

Adult↗