In vivo changes in the intestinal lipid peroxidation and the crypt response to whole-body gamma irradiation in diethylnitrosamine-treated mice

Studies were carried out to elucidate lipid peroxidation and crypt survival in the small intestinal mucosa of mice pretreated per os with diethylnitrosamine (DENA) and whole-body gamma irradiated. Results show that DENA lowered the total value of mean lethal radiation dose for crypt cells, and the agent was enable to sensitize crypts to gamma-rays. Present data suggest that gamma radiation- and/or DENA-induced pro-oxidant shift(s) is a risk factor for crypt survival.     

Chosen environmental factors and their effect on the incidence of overweight and obesity in the population of Podlasie Region

The study was conducted to evaluate chosen environmental factors that may contribute to overweight or obesity among the population of Podlasie. Socio-economic status, physical activity and the use of condiments and medications were assessed. The investigations, treated as preliminary, used questionnaire technique and involved 150 volunteers (132 women and 18 men), aged 18-69 years (women; mean 37.4 +/- 12.50) and 18-62 (men; mean 30.0 +/- 11.03). In the majority of subjects the first symptoms of obesity appeared in childhood and puberty. Overweight was familial in 69.6% of women and in 77.7% of men (statistically significant risk factor), which could reflect genetic load or similar lifestyle. Frequency and type of recreational and sports activity were evaluated. Over 77% of the subjects examined declared little and inadequately matched physical activity. The knowledge of health state was unsatisfactory and obesity was considered only in cosmetic terms. Prophylactic actions should intend to educate the whole society, propagate healthy lifestyle and to increase physical activity. People with overweight and obesity should tend to normalise body mass and thus to improve metabolic parameters and general feeling.     

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.     

Discrete glioneuronal malformative lesions in the foetal and infantile cerebral cortex

Microdysgenesis is a term describing microscopic cortical cytoarchitectural abnormalities. Histologically this change shows an irregular glioneuronal tissue combination forming an abnormal structure of the cortex. The pathological features of this malformation are subtle and less well defined than other more distinctive cortical malformations. The clinical significance of these discrete glioneuronal malformations is controversial. Microscopic dysgenetic changes have been reported in cases with intractable epilepsy but similar changes may be seen in neurologically normal adults. The purpose of our study was the investigation of microdysgenetic lesions in the developing nervous system with regard to normal neuronal migration, differentiation and maturation. The post-mortem routine investigated foetal and infantile brains which were analysed histologically for the presence of discrete cortical malformations. A wide spectrum of cytoarchitectural glioneuronal malformations was found in the investigated material. We observed leptomeningeal glioneuronal heterotopias, subpial bands of heterotopic neurones, nests of ectopic neurones in the first cortical layer, neuronal and glial clusters, small foci with irregularity of laminar structure of the cortex. Microdysgenetic changes arose from an insult occurring in the later stages of cortical development and influencing the normal fate of neuroglial cells. Various types of focal morphological and cytoarchitectonial developmental abnormalities have been associated with behavioural and neuropsychological deficits in older infants.     

A case of pseudo-aprosencephaly

We present a case of rare, severe brain malformations. In a microcephalic premature newborn only a small structure found in the base of the cranium corresponded to the prosencephalic part of the brain. The basal ganglia were lacking and the cortico-subcortical area changed into empty vesicles with only small fragments of cortical stripe. This picture authorises us to speak on the probably complex pathomechanism of anomalies: genetically caused malformations including underdevelopment of telencephalic nuclei and additional occurrence of extrinsic lesions leading to pseudo-aprosencephaly formation.     

N-methyl-d-aspartate receptor-mediated processing of beta-amyloid precursor protein in rat hippocampal slices: in vitro--superfusion study

Abnormal proteolytic degradation of the beta amyloid precursor protein (beta-APP) may result in accumulation of potentially neurotoxic beta amyloid (betaA). The role of various receptors in the regulation of beta-APP processing has been suggested. This study aimed to determine how NMDA receptors and Ca2+ ions regulate proteolysis of beta-APP in rat hippocampus in vitro. Adult rat hippocampal slices were superfused with NMDA-containing media, and immunoreactivity of soluble beta-APP derivatives was detected in dialysates. Application of 100 microM and 250 microM NMDA for 20 min in Ca2+-containing medium induced dose-dependent release of aminoterminal beta-APP derivatives, and a fragment of Abeta sequence, whereas carboxy-terminal fragments of beta-APP were only slightly detected. This indicates activation of beta-APP processing, and release of its soluble cleavage products. This effect was inhibited by NMDA receptor antagonist 1 microM MK-801 and 100 microM CPP in Ca2+-free medium, thus indicating that NMDA receptors and calcium ions mediate proteolytic non-amyloidogenic degradation of the beta-APP.     

Priming effects of GM-CSF, IFN-gamma and TNF-alpha on human neutrophil inflammatory cytokine production

Identifying and evaluating the priming agents for cytokine release by neutrophils might be helpful in controlling the innate immune response of the host. In the present study we examined the role of granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) as priming agents for interleukin (IL)-1beta, IL-6 and TNF-alpha production by stimulated neutrophils from control subjects and malignant melanoma patients. When the cells from controls and patients were preincubated with primer agents, opsonized zymosan-stimulated inflammatory cytokine production was enhanced. The major neutrophil-priming factor for IL-6 secretion by polymorphonuclear leukocytes (PMNs) in the control and patient groups was TNF-alpha. However, GM-CSF and IFN-gamma are also significant primers. GM-CSF priming was critical for the release of TNF-alpha from PMNs in control and melanoma patients. The ability of GM-CSF, IFN-gamma and TNF-alpha to serve as effective priming agents for inflammatory mediator production by PMNs revealed a new role for these cytokines in the innate immune response of the melanoma-bearing host.     

The search for optimal treatment in relapsed and refractory acute myeloid leukemia

Despite the significant progress in the treatment of AML during the last 5-10 years, 20-40% of patients still do not achieve remission with standard induction therapy. In addition, 50-70% of patients in CR are likely to relapse. A major limitation of successful AML therapy is intrinsic or acquired drug resistance. Several pharmacological inhibitors of mechanisms inducing chemoresistance in leukemic cells have been investigated. New cytotoxic drugs, agents with novel mechanisms of action, and new treatment strategies are currently being investigated. The management of refractory or relapsed AML patients is reviewed in this study.     

Serum arginase activity in postsurgical monitoring of patients with colorectal carcinoma

BACKGROUND: Colorectal carcinoma (CRC) is one of the most common malignancies. In the current work, the role of arginase as a diagnostic marker in patients with recurrent CRC and colorectal liver metastases (CRCLM) was studied. METHODS: Arginase activity was monitored in serum from 40 patients with primary CRC and from 100 patients with CRCLM. Blood was taken before and after patients underwent tumor resection. Studies were conducted for 3 years. RESULTS: Preoperative arginase activity in serum from patients with CRC and CRCLM was much greater compared with the arginase activity in serum from healthy control blood donors. One and two cut-off levels of increased arginase activity were observed in patients with CRC and CRCLM, respectively. After patients underwent tumor resection, the arginase activity decreased to normal values in both patients with CRC and patients with CRCLM. Activity levels remained low in patients who did not develop recurrent CRC or CRCLM (first or second). In patients who developed subsequent recurrences or metastases that appeared after surgery, during 3 years of surveillance, a significant rise in serum arginase activity was observed. The clinical prognosis for patients was worst when the postoperative serum arginase activity was very high, because those patients more often developed second liver metastases or died. CONCLUSIONS: The authors conclude that the determination of serum arginase activity may be a complementary test to confirm the occurrence of CRC and may be useful for the early diagnosis of patients who develop recurrent CRC and/or CRCLM.     

Tic syndrome

A tic is an involuntary, sudden, rapid, recurrent, nonrrhythmic, stereotyped, motor movement or vocalization. This paper reviews clinical, pathophysiological, epidemiological and treatment issues of tic disorders. The clinical presentation of tic disorders with simple and complex motor or vocal tics is reviewed in detail. The most common psychiatric comorbid conditions, such as personality disorder (PD), Obsessive-Compulsive Disorder (OCD), Self-Destructive Behavior (SDB) and Attention Deficit Hyperactivity Disorder (ADHD) are presented too. All forms of tics may be exacerbated by anger or stress, but they are usually markedly diminished during sleep. Premonitory feelings or "sensory experiences", which are distinct from the actual motor or phonic tics and precede the tics, occur in over 80% of tic-patients and in 95% of patients with Gilles de la Tourette Syndrome (GTS). The American Psychiatric Association recognizes three types of tic disorders on the basis of clinical criteria: Transient Tic Disorder, Chronic Motor or Vocal Tic Disorder and GTS. The diagnostic criteria for these types are described. According to epidemiological data, up to 10% of children have at least somewhere a transient tic disorder. The onset of tics, whether simple or multiple, occurs at approximately 7 years of age. The accepted prevalence figure for GTS is 0.05-3%. Although tics can appear as the result of brain injury, Huntington chorea or encephalitis, they are most commonly idiopathic. Genetic factors appear to be present in many but not in all cases of tic disorders. Autosomal dominant, sex-linked models or semirecessive-semidominant-oligogenic models have been considered. Based on the review of the literature we believe that tic disorders are related to altered neurotransmitter function within the CNS, especially that the functional abnormality is somehow related to dopaminergic mechanism. Several authors have recently investigated the possible role of autoimmune response to streptococcal infection in the pathogenesis of tics. The differential diagnosis of tics is reviewed in detail. Above all tics represent a social disability. The ability to tolerate tics varies greatly from one individual to another, and the need for treatment is better defined by the patient than by the physician. Mild cases do not need be treated. Ideally, management should be multidisciplinary and can range from educative to supportive means or to intricate pharmacological interventions. The major form of treatment of the motor or vocal symptoms continues to be based on high-potency "typical" neuroleptics (tiaprid, pimozide, haloperidol), which induce a wide range of potentially serious side effects. In everyday practice we prefer to start with an "atypical" neuroleptic drug--for example, olanzapin (5-10 mg/day), risperidone or clozapine. Other drugs, such as clonidin or pergolid are widely used but their efficiency is still questionable. SSRIs (sertaline, citalopram, fluoxetin, fluvoxamine) or other antidepressants (clomipramine) have been used in treatment of psychiatric comorbid conditions, too. Botulinum toxin injections have proved useful in tics, targeting at the symptoms of blepharospasm, in neck and facial muscles.