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Biomedical subjects

Jari Honkaniemi

Publications and source records attributed to Jari Honkaniemi.

10 recordsLinked to original sources

Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of i.v. haloperidol in treatment of acute migraine headache in a double-blind, randomized, placebo-controlled study design. BACKGROUND: Neuroleptics are mainly used as antiemetics in acute migraine. In a previous open trial haloperidol was effective in relieving migraine pain. DESIGN: Patients were randomized into 2 groups receiving intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of normal saline alone. Pain was assessed by visual analogue scale (VAS) before and 1 to 3 hours after the infusion. If the patient felt no relief in pain intensity 1 to 3 hours after the infusion and had received placebo, he/she then received haloperidol infusion as an open trial. The open trial also included 7 patients who refused from the placebo-controlled trial. About 1 month after the infusion the patients were contacted by telephone and interviewed about the side effects of the treatment. RESULTS: Forty patients were enrolled into the double-blind, placebo-controlled study. Before the infusion the VAS values were 7.7 in the haloperidol and 7.2 in the placebo group. After the infusion the VAS values were 2.2 in the haloperidol and 6.3 in the placebo group (P < .0001). Significant pain relief was achieved in 80% of the patients treated with haloperidol, whereas only 3 patients (15%) responded to placebo (P < .0001). Seventeen patients treated with placebo without response together with 7 patients who refused from the placebo-controlled study participated in the open trial. In this group VAS declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief. The most common side effects caused by haloperidol were sedation and akathisia, the latter being more troublesome. These effects were very common in patients participating in the double-blind (80%) and open (88%) trials. Sixteen percent of the patients considered the side effects intolerable and would not like the migraine attacks to be treated with haloperidol in the future. Three patients (7%) returned to the emergency ward because of a relapse. CONCLUSIONS: This study shows that i.v. haloperidol is very effective in relieving migraine-associated pain. Because the majority of the patients had taken other medication without response, haloperidol appears to be an effective rescue medication even when other types of treatment have failed. Relapses are rare, but side effects are common, limiting the use of haloperidol in some patients.

Acute Disease↗

Expression of carbonic anhydrases II, IV, VII, VIII and XII in rat brain after kainic acid induced status epilepticus.

Carbonic anhydrases (CAs) are important enzymes in the central nervous system (CNS), where they participate in regulating cerebrospinal fluid (CSF) secretion, blood-brain barrier and glial cell function. Using RT-PCR we found CA XII mRNA in rat and mouse brain. Cloning of rat CA XII revealed 94% homology with the mouse CA XII. To map the putative functional roles of different CAs, we studied the expression and localization of CA II, CA IV, CA VII, CA-related protein (CA-RP) VIII and CA XII mRNAs in rat brain after kainic acid induced epileptic seizures using Northern blot analysis and in situ hybridization. The expression of CA IV, CA VII and CA-RP VIII was somewhat similar: they were expressed in the cortex, hippocampus and midbrain structures and their expression did not change after the kainic acid treatment. The expression of CA II was concentrated in the white matter structures, which is in line with the preferential expression of CA II in the oligodendrocytes. High levels of CA II mRNA were also detected in the choroid plexus. Surprisingly, CA II was induced 3-12 h after seizures in the vulnerable CA1 region. CA XII was expressed in dentate granule cells, cortex and choroid plexus. Kainic acid stimulated CA XII expression throughout the cortical layer I. The observed hippocampal induction of CA II may indicate a pro-apoptotic and/or epileptogenic role of CA II after prolonged seizures. The physiological significance of the observed cortical induction of CA XII remains obscure. Cytosolic CA II is known to participate in CSF secretion, and the high expression of CA XII in the choroid plexus suggests an analogous role for this membrane-bound isozyme.

Animals↗

GABA and glutamate transporters are expressed in human platelets.

GABA and glutamate are the major neurotransmitters in the human central nervous system. Disturbances in these transmitter systems have been suggested to influence a variety of neurological and psychiatric diseases. Human platelets have been used as a model for neural amino acid transport, although it has not been known exactly which transporters participate in the transport process. In this study, we identify with reverse transcription-polymerase chain reaction (RT-PCR) BGT-1 and EAAT3 as transporters for GABA and glutamate, respectively. We also show that platelets contain transporters for dopamine, taurine and creatine. The cloning of these transporters confirms that blood platelets can be used as a model for neurotransmitter transport in the CNS.

Adult↗

Expression of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in the brain during experimental group B streptococcal meningitis.

We performed mRNA in situ hybridization for TNF-alpha and IL-1beta from infant rats with group B streptococcal meningitis. Induction of both cytokines was seen in the ependyma and the meninges at 4 h. Both cytokines were expressed in the brain parenchyma at 12 h. Induction of IL-1beta mRNA was seen in vessels within the brain cortex. Neutrophilic infiltrate at all time points examined was minimal and could not account for the observed cytokine expression.

Animals↗

Intranasal administration of human IL-6 increases the severity of chemically induced seizures in rats.

Here we study the role of a pleiotropic pro-inflammatory cytokine, interleukin-6 (IL-6), in epilepsy. To examine this problem, we used human recombinant IL-6 applied intranasally (400 ng/40 microl) to rats 1h before seizures induced by systemic injection of pentylenenetrazole (PTZ, 75 mg/kg). Overall, compared to the saline-treated control animals (n = 11 in each group), IL-6-treated rats demonstrated elevated levels of IL-6 in the frontal lobe (measured by ELISA) and increased severity of PTZ-induced seizures (shorter latency, longer duration and higher mortality). Our findings show that IL-6 plays a pro-convulsant role in the brain and suggest that the IL-6 system may be a novel target for the development of anticonvulsant drugs.

Administration, Intranasal↗

Cloning and expression of short interspersed elements B1 and B2 in ischemic brain.

Global ischemia causes an extensive cell death 3 days after the ischemia in the CA1 region of the hippocampus, which is preceded by induction of a spectrum of genes with both neuroprotective and detrimental properties. This delayed cell death has been suggested to be mainly caused by programmed cell death. Here we applied differential display to characterize transcripts induced by global ischemia after 1 day in Mongolian gerbils, when the cells in the CA1 region are still viable, but initiating the cell death pathway. One of the cloned transcripts turned out to be a repeat sequence termed SINE B2. We also cloned the other member of the SINE family, SINE B1, and found it also to be slightly induced by ischemia in the CA1 region. The SINE repeat regions are not translated and their role in ischemia may be related the neurons' attempt to cope with decreased translational levels and/or genomic reorganization. Together with the previous data demonstrating the inducibility of the SINE transcripts using in vitro stress models, the present study shows that SINE transcripts are stress-inducible factors in the central nervous system.

Animals↗