A case report: Pavlovian conditioning as a risk factor of heroin 'overdose' death

BACKGROUND: The authors present a case illustrating a mechanism leading directly to death which is not rare but has received little attention. CASE PRESENTATION: The case was evaluated by autopsy, investigation of morphine concentration in the blood, and clinical data. The heroin dose causing the 'overdose' death of a young man who had previously been treated a number of times for heroin addiction did not differ from his dose of the previous day taken in the accustomed circumstances. The accustomed dose taken in a strange environment caused fatal complications because the conditioned tolerance failed to operate. The concentration of morphine in the blood did not exceed the level measured during earlier treatment. CONCLUSION: These results are in line with the data in the literature indicating that morphine concentrations measured in cases of drug-related death do not differ substantially from those measured in cases where the outcome is not fatal. A knowledge of the conditioning mechanism can contribute to prevention of fatal cases of a similar type. The harm reduction approach places great stress on preventive intervention based on data related to drug-related death

Association study of the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia

BACKGROUND: Brahma (BRM) is a key component of the multisubunit SWI/SNF complex, a complex which uses the energy of ATP hydrolysis to remodel chromatin. BRM contains an N-terminal polyglutamine domain, encoded by a polymorphic trinucleotide (CAA/CAG) repeat, the only known polymorphism in the coding region of the gene (SMARCA2). We have examined the association of this polymorphism with schizophrenia in a family-based and case/control study. SMARCA2 was chosen as a candidate gene because of its specific role in developmental pathways, its high expression level in the brain and some evidence of its association with schizophrenia spectrum disorder from genome-wide linkage analysis. RESULTS: Family-based analysis with 281 complete and incomplete triads showed that there is no significant preferential transmission of any of the alleles to the affected offspring. Also, in the case/control analysis, similar allele and genotype distributions were observed between affected cases (n = 289) and unaffected controls (n = 273) in each of three Caucasian populations studied: French Canadian, Tunisian and other Caucasians of European origin. CONCLUSION: Results from our family-based and case-control association study suggest that there is no association between the trinucleotide repeat polymorphism within SMARCA2 and schizophrenia

Triptofán és bizonyos metabolitjainak koncentrációjának meghatározása Creutzfeldt-Jakob betegeknél = The assessment of concentrations of certain tryptophan metabolites in Creutzfeldt-Jakob disease

The kynurenine (KYN) pathway (KP), also known as the route where more than 95% of the tryptophan (TRP) is metabolized, in its steps of catabolism forms different metabolites which contribute to the neuroprotective–neurodegenerative changes in central nervous system. For this reason, TRP metabolism is extensively studied in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease), where the neurologically active metabolite concentration changes are followed. Kynurenic acid (KYNA), which is an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist, is considered to be a neuroprotective agent. In the present study TRP, KYN and KYNA were determined from human serum and cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD) and age- and gender-matched controls, using high performance liquid chromatography (HPLC) applying UV and fluorescent detectors. The developed method was optimized and validated according to the International Congress Harmonization Guidelines. The precision and recovery values ranged between 1.60-4.36%, 81.61-101.09%, respectively. There were no differences between the groups with regard all the measured metabolites. The application of the developed validated method enabled the simultaneous determination of certain metabolites of the KP of TRP metabolism, but no evident alterations were found in patients with CJD

Plasma and cerebrospinal fluid tau and neurofilament concentrations in rapidly progressive neurological syndromes: a neuropathology-based cohort

Background and purpose: Cerebrospinal fluid (CSF) tau and neurofilament light chain (NF‐L) proteins have proved to be reliable biomarkers for neuronal damage; however, there is a strong need for blood‐based tests. Methods: The present study included 132 autopsy cases with rapidly progressive neurological syndromes, including Alzheimer disease (AD) (21), sporadic (65) and genetic (21) Creutzfeldt–Jakob disease (CJD), 25 cases with vascular, neoplastic and inflammatory alterations, and additionally 18 healthy control individuals. CSF tau and NF‐L concentrations were measured by enzyme‐linked immunosorbent assay. Plasma tau and NF‐L concentrations were measured using ultra‐sensitive single molecule array technology. Results: Plasma and CSF tau (R = 0.59, P < 0.001) and NF‐L (R = 0.69, P < 0.001) levels correlated significantly (Spearman test). Plasma tau and NF‐L levels were significantly higher in all disease groups compared to healthy controls (P < 0.001). Receiver operating characteristic curves were used and area under the curve values for comparisons with controls were 0.82 (AD), 0.94 (sporadic CJD), 0.92 (genetic CJD) and 0.83 (other neurological disorders) for plasma tau and 0.99, 0.99, 1.00 and 0.96 for plasma NF‐L, respectively. Molecular subtyping of sporadic CJD showed a strong effect (linear logistic regression) on plasma tau (P < 0.001) but not NF‐L levels (P = 0.19). Conclusion: Plasma tau and NF‐L concentrations are strongly increased in CJD and show similar diagnostic performance to the corresponding CSF measure. Molecular subtypes of sporadic CJD show different levels of plasma tau. Although not disease‐specific, these findings support the use of plasma tau and NF‐L as tools to identify, or to rule out, neurodegeneratio

Desensitization of Capsaicin-Sensitive Afferents Accelerates Early Tumor Growth via Increased Vascular Leakage in a Murine Model of Triple Negative Breast Cancer

There is growing interest in the role of nerve-driven mechanisms in tumorigenesis and tumor growth. Capsaicin-sensitive afferents have been previously shown to possess antitumoral and immune-regulatory properties, the mechanism of which is currently poorly understood. In this study, we have assessed the role of these terminals in the triple negative 4T1 orthotopic mouse model of breast cancer. The ultrapotent capsaicin-analogue resiniferatoxin (RTX) was used for the selective, systemic desensitization of capsaicin-sensitive afferents. Growth and viability of orthotopically implanted 4T1 tumors were measured by caliper, in vivo MRI, and bioluminescence imaging, while tumor vascularity and protease enzyme activity were assessed using fluorescent in vivo imaging. The levels of the neuropeptides Calcitonin Gene-Related Peptide (CGRP), Substance P (SP), and somatostatin were measured from tumor tissue homogenates using radioimmunoassay, while tumor structure and peritumoral inflammation were evaluated by conventional use of CD31, CD45 and CD3 immunohistology. RTX-pretreated mice demonstrated facilitated tumor growth in the early phase measured using a caliper, which was coupled with increased tumor vascular leakage demonstrated using fluorescent vascular imaging. The tumor size difference dissipated by day seven. The MRI tumor volume was similar, while the intratumoral protease enzyme activity measured by fluorescence imaging was also comparable in RTX-pretreated and non-pretreated animals. Tumor viability or immunohistopathological profile was measured using CD3, CD31, and CD45 stains and did not differ significantly from the non-pretreated control group. Intratumoral somatostatin, CGRP, and SP levels were similar in both groups. Our results underscore the beneficial, antitumoral properties of capsaicin sensitive nerve terminals in this aggressive model of breast cancer, which is presumed to be due to the inhibition of tumor vascular bed disruption. The absence of any difference in intratumoral neuropeptide levels indicates non-neural sources playing a substantial part in their expression

Nők a seregben : katonanők helyzete a Magyar Honvédségben

A diplomamunkám témája A nők a seregben – Katonanők helyzete a Magyar Honvédségben. A kutatásom célja: egy általam kiválasztott intézmény női állományának helyzetének elemzése és összefoglalása, a szervezet jellemzőinek megfogalmazása