Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam

The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED(50)=39.8 nmol) and allopregnanolone (ED(50)=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED(85) dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy.     

Rapid desensitization of receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) in chick cerebral cortex

Pituitary adenylate cyclase-activating polypeptide (PACAP38) potently stimulates cyclic AMP formation in slices of chick cerebral cortex. One- to fifteen-minute pretreatment of slices with 30 nM PACAP38 led to a time-dependent attenuation (when compared with values observed in the control tissue) of the cyclic AMP response produced by subsequent re-stimulation with 1 microM PACAP38. Concentration-response curve for restimulation with PACAP38 applied at 0.01-1 microM to tissue slices preincubated for 15 min with 30 nM PACAP38 revealed dose-dependent decreases in subsequent cyclic AMP responses by 16-37%. It is concluded that in chick cerebral cortex, the receptors mediating PACAP-driven cyclic AMP responses (PAC1 receptors) undergo rapid homologous desensitization.     

Intrathecal baclofen in severe spasticity due to multiple sclerosis

Intrathecal administration of baclofen via programmable pump is a highly effective treatment method in severe spasticity resistant to oral medications. The authors describe a case of severe spasticity with tetraplegia and painful (> 10 a day) muscle spasms in the upper and lower limbs and paraspinal muscles, in a patient with clinically definite diagnosis of multiple sclerosis (MS). The 34-year-old female patient with a 15-year history of MS, suffering from lower limb spasticity with pes equinovarus since 1995, was treated with very good results with botulinum toxin injections of calf muscles (14 sessions of Dysport 1500iu till 2002). In the early 2002 she developed tetraplegia with severe, generalized and intractable spasticity. After 4 months of ineffective polytherapy (with high doses of oral baclofen, tizanidine, gabapentine, clonidine, diazepam) and the patient's enormous sufferings (she could neither sit up nor voluntarily change her position in bed), a programmable baclofen pump (Medtronic) was implanted. As soon as a few days after the surgery she could stand, sit and move voluntarily, her painful spasms disappeared, and her bladder catheter was removed. At a 6-month follow-up the effect was stable--she was able to walk a long distance outdoors with the aid of a crutch. The daily dose of the drug is 500 micrograms. No side effects of complications were noted.     

The frequency of diagnosis of catatonic schizophrenia in hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Boleslawiec (1958-1999)

AIM: The analysis of the data from the psychiatric hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Boles?awiec (1958-1999) proved a decrease in frequency of diagnosis of catatonic schizophrenia, what could testify to a decrease in morbidity with this form of schizophrenia. METHOD AND RESULTS: Basing on the facts from scientific literature there was ascertained that the decrease in frequency of diagnosis of catatonic schizophrenia is connected with following causes: firstly, with the changes in nozology, secondly, with the introduction of a new form of therapy and finally, with the fact that here psychological and sociological factors exist which eliminate catatonia as the most expressive form of schizophrenia.     

Mumps in Poland in 2000

A total of 17,548 mumps cases were reported in Poland in 2000. A 5-fold decrease in incidence of the disease (from 233.4 to 45.4 per 100,000 population) was noted, when compared with 1999. Approximately 4.8% of mumps cases were hospitalized (849 cases). The majority of the reported cases were children aged 5-9 (51.4% of all cases). In all voivodships the incidence was lower than in previous years. The probable cause of the decline of mumps cases was a marked amelioration of MMR vaccination coverage among 3-year old children. The MMR vaccine is not included into the national program of immunization, the vaccination is recommended for 2-year and 7-year old children.     

Levels of organochlorine insecticides in Polish women's breast adipose tissue,in years 1997-2001

Although manufacture and use of chlorinated insecticides was banned or severely restricted in most of countries in the 1970s, the residues of these compounds are still detected in various environmental matrices all over the world. Their highest levels are found in adipose tissue of beings at the top of food chain, including humans. Levels of persistent organochlorine compounds in human specimens are monitored by numerous scientific organizations in various countries, including Poland. The purpose of the study was to survey the current levels of selected organochlorine insecticides (isomers alpha-, beta-, gamma-, delta-HCH, o,p'- and p,p'-DDT, DDE i DDE, oxy-chlordane and heptachlor) in women's breast adipose tissue which can be an indicator of body burden. A total of 67 samples of adipose breast tissue collected between 1997 and 2001 from non-cancer patients, aged from 15 to 74 years have been analyzed. The analytical procedure included extraction, clean-up and analysis by means of GC-ECD with GC-MS confirmation. In all the samples analyzed p,p'-DDE, p,p'-DDT and beta-HCH were present (mean values, expressed as mg/kg of fat: 0.7700, 0.0720, and 0.0635 respectively) with p,p'-DDE, found to be dominant analyte. The levels of the remaining compounds, were usually about or below the method quantification limits (from 0.0025 to 0.0060 mg/kg of fat). The results for DDTs and beta-HCH for the oldest group (above 50 years) were 2.1 to 3.6 times higher than the youngest group (below 39 years). The results obtained in this study are similar to those reported in analogous samples collected from women living in other European countries with similar climate and history or organochlorines usage as well as in the USA. The presence of some organo-chlorine insecticide residues in women's adipose tissue, even those, who were born even 10-15 years after most countries introduced severe restrictions or banned the use of these compounds may be cause for anxiety. That is due to the potential of these compounds to promote toxic effects, including disrupting the human endocrine system.     

Coexistence of diffuse large B-cell lymphoma within pontocerebellar angle schwannoma

We present an unusual case of diffuse large B-cell lymphoma within pontocerebellar angle schwannoma in 62-year-old woman. The patient suffered for 5 months with V, VII and VIII nerves paresis and with cerebellar ataxia. CT scan demonstrated large hyperdensive mass in cerebellopontine angle translocating cerebellar hemisphere and cerebral trunk. The patient was subjected to surgery and the tumour was removed totally by suboccipital retromastoidal right craniectomy approach. Histopathological examination revealed schwannoma infiltrated with high grade B-cell lymphoma. The patient did well following surgery without any other lymphoma manifestations, and she died from a heart attack 20 months later. Solitary lymphoma of pontocerebellar angle coexisting with schwannoma is an unusual finding, thus our case is the first report.     

Cystic meningioma: report of three cases

Meningioma with cystic component is not a commonly encountered tumor. We report three patients with cystic meningioma histologically confirmed. Tomographic images of these tumours resembled those of a glial or metastatic origin with cystic or necrotic changes and were easily confused. In a 2-year period (1997-1999) in our Department we had three patients with cystic meningioma who account for 5.4% of all patients with meningiomas we have.     

Lack of association between 141C Ins/Del promoter polymorphism of DRD2 gene and schizophrenia

Results of family studies show the importance of genetic factors in etiopathogenesis of schizophrenia. Susceptibility to the disease is probably due to an interaction of many genes. This association study was conducted to investigate frequencies of alleles and genotypes in a group of patients with schizophrenia and in healthy controls. We examined DRD2 gene promoter polymorphism--insertion or deletion of the cytosine in the position -141 of 5'-flanking region of this gene. No relationship between the polymorphism under study and schizophrenia has been found.     

Lack of association between VNTR polymorphism of DAT gene and schizophrenia

The substantial importance of genetic factors in the etiology of schizophrenia was demonstrated in many studies. The complex model of disease inheritance seems to be the most probable, involving epistatic interaction of many genes. Association studies are based on the analysis of the so-called candidate genes, which are coding for neurotransmitter receptors, neurotransmitter transporters and enzymes involved in their metabolism. In the present work the results of an association study of VNTR polymorphism of dopamine transporter gene (DAT) in schizophrenia are presented. This polymorphism is characterised by a different number of tandem repeats (VNTR) within the 3'-untranslated region of gene. In Caucasians the 40 base pair motif has 3 to 11 repeats, the most common (about 90%) are alleles containing 9 and 10 repeats. In the present study no association between the polymorphism studied and schizophrenia was found.