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.     

Pharmacological effects of lavandulifolioside from Leonurus cardiaca

Lavandulifolioside was detected for the first time in Leonurus cardiaca var. vulgaris [Moench] Briquet (Lamiaceae). The isolation was performed from the butanolic extract of the aerial parts and the identification by NMR and MS. The pharmacological properties of lavandulifolioside consist of significant negative chronotropism, prolongation of the P-Q, Q-T intervals and QRS complex, and decrease of blood pressure. Contrary to the butanolic extract lavandulifolioside did not reduce the spontaneous locomotor activity. In conclusion, the pharmacological pattern of lavandulifolioside did not explain the pharmacological effects of L. cardiaca L. alone.     

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.     

Projections from the amygdaloid complex to the claustrum and the endopiriform nucleus: a Phaseolus vulgaris leucoagglutinin study in the rat

The claustrum and the endopiriform nucleus contribute to the spread of epileptiform activity from the amygdala to other brain areas. Data of the distribution of pathways underlying the information flow between these regions are, however, incomplete and controversial. To investigate the projections from the amygdala to the claustrum and the endopiriform nucleus, we injected the anterograde tracer Phaseolus vulgaris leucoagglutinin into various divisions of the amygdaloid complex, including the lateral, basal, accessory basal, central, anterior cortical and posterior cortical nuclei, the periamygdaloid cortex, and the amygdalohippocampal area in the rat. Analysis of immunohistochemically processed sections reveal that the heaviest projections to the claustrum originate in the magnocellular division of the basal nucleus. The projection is moderate in density and mainly terminates in the dorsal aspect of the anterior part of the claustrum. Light projections from the parvicellular and intermediate divisions of the basal nucleus terminate in the same region, whereas light projections from the accessory basal nucleus and the lateral division of the amygdalohippocampal area innervate the caudal part of the claustrum. The most substantial projections from the amygdala to the endopiriform nucleus originate in the lateral division of the amygdalohippocampal area. These projections terminate in the central and caudal parts of the endopiriform nucleus. Lighter projections originate in the anterior and posterior cortical nuclei, the periamygdaloid cortex, the medial division of the amygdalohippocampal area, and the accessory basal nucleus. These data provide an anatomic basis for recent functional studies demonstrating that the claustrum and the endopiriform nucleus are strategically located to synchronize and spread epileptiform activity from the amygdala to the other brain regions. These topographically organized pathways also provide a route by means of which the claustrum and the endopiriform nucleus have access to inputs from the amygdaloid networks that process emotionally significant information.     

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.     

Percutaneous transluminal angioplasty of extracranial vertebral artery stenosis--a case report

Due to improvement in intravascular therapeutic procedures significant stenoses of vertebral and basilar arteries can presently be treated by means of percutaneous transluminal angioplasty (PTA). The reported case was a 34-year-old man with symptomatic stenosis of the distal left vertebral artery and hypoplastic right vertebral artery. The patient underwent PTA and the lesion was sufficiently dilated. No complications occurred during or after the procedure. After a year duplex Doppler follow-up examination showed normal blood flow and patency of both vertebral arteries. PTA may prove to be a useful therapeutic option in patients with symptoms of vertebro-basilar insufficiency.     

Evaluation of blood flow velocity and cerebrovascular reactivity in patient with posterior circulation stroke

The aim of our study was to determine the type of blood flow disturbances and cerebrovascular reactivity of major anterior and posterior circulation cerebral vessels in patients with posterior stroke (POCI). The examined group consisted of 17 patients, mean age 57 +/- 12 yr, with posterior circulation infarct. Neurological examination, brain CT and Doppler examination including evaluation of BFV and CVR of MCA, PCA and VA was performed in each patient. Doppler examination was done using Pioneer TC 2020 and capnograph Tidal Wave sp Novametrix. RESULTS: BFV of ICA's, MCA's, ACA's and PCA's were diminished while BFV of VA's were significantly diminished in the examined patients compared to healthy controls. CVR of MCA in posterior circulation stroke patients was significantly lower compared to controls. CVR of PCA and VA was significantly lower compared to CVR of MCA in patients with posterior circulation stroke. CONCLUSION: Impairment of CVR, especially in posterior circulation, plays an important role in posterior circulation stroke pathogenesis.