HIGH-SENSITIVITY C-REACTIVE PROTEIN, POSSIBLE BIOMARKER FOR DEPRESSION IN ELDERLY POPULATION.

CONTEXT: The immune system has an important role in the etiology of depression, through the pro-inflammatory cytokines and acute phase protein mechanisms. In elderly people, frequent association between depression and medical conditions leads to a difficult psychiatric diagnosis, becoming necessary to determine a specific biological marker for this category of population. C-Reactive Protein (CRP) did not prove to have a high level of validity, but higher levels of high-sensitivity C-Reactive Protein (hs-CRP) were found to be associated both with cardiovascular disease and depressive disorder, through a bidirectional relationship. OBJECTIVES: To investigate the possible association between a major depressive episode and levels of inflammatory markers among a population of elderly. SUBJECTS AND METHODS: A prospective study on a sample of 82 individuals aged over 65 years, who presented for laboratory evaluations in an outpatient setting. They were recorded socio-demographic and clinical data; depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. Blood samples were collected and analyzed according to the protocol of the study. RESULTS: Anxiety, identified in 57 persons, was not statistically significant correlated with the levels of inflammatory markers. For depressive disorder (37 subjects), both CRP and hs-CRP were significantly higher, with an almost medium effect size. CONCLUSIONS: The high levels of CRP and hs-CRP are associated with the presence of depression in elderly patients, but not with the anxiety. Further and complex studies need to validate these findings on this group of age.

PROLACTIN LEVEL IN PATIENTS WITH FIRST EPISODE SCHIZOPHRENIA TREATED FOR ONE YEAR WITH ATYPICAL ANTIPSYCHOTICS.

CONTEXT: Atypical antipsychotics (AAs) are the first-line treatments for schizophrenia, schizoaffective disorder and bipolar disorder. However, they are now extensively utilized as off label in a myriad of diseases despite their frequently serious metabolic side-effects and hyperprolactinemia. OBJECTIVE: The purpose of our study was to observe long-term (one year) prolactin level change in first episode schizophrenia patients treated with one of the four AAs: olanzapine, quetiapine, amisulpride, ziprasidone. DESIGN: This study is an analysis of the prolactin level associated with the atypical antipsychotics used in European First Episode Schizophrenia Trial (EUFEST) study. SUBJECTS AND METHODS: Seventy-three first episode schizophrenia patients from the 113 patients, randomized to one of the four AAs treatment arms. Prolactin level was obtained at baseline, 6 and 12 months for all the four AAs. Analyses have been done for each antipsychotic separately for each sex. RESULTS: For the male patients neither of the four antipsychotics have been associated with a statistically significant increase of prolactin level in the entire study (p>0.05). In case of the female patients, treatment with olanzapine (p=.021) and ziprasidone (p=.005) has been associated with a decrease of prolactin level in one year compared with baseline. CONCLUSIONS: In both men and women, the administration of these four AAs is not associated with the increase of prolactin levels, moreover, in women's case, there is a reduction of prolactin values at administration of Olanzapine and Ziprasidone. These results are optimistic, suggesting that long term administration of these antipsychotics is safe regarding prolactin level.

WEIGHT GAIN AND ANTIPSYCHOTICS. DATA FROM EUFEST STUDY.

CONTEXT: Schizophrenia is a chronic disease most frequently necessitating lifelong antipsychotic treatment. Selecting which antipsychotic is to be prescribed in an individual schizophrenia patient represents an important clinical decision that need to take into account efficacy and side effects. OBJECTIVE: Evaluating weight gain related with one year antipsychotic treatment in antipsychotic naive first-episode schizophrenia patients. DESIGN: This study is an analysis of weight gain associated with typical or atypical antipsychotics used in European First Episode Schizophrenia Trial (EUFEST) study. SUBJECTS AND METHODS: 113 first episode naïve antipsychotic schizophrenia patients included in EUFEST - Romanian cohort, who were randomized to one of the 5 treatment arms. Weight was obtained at baseline, 3, 6, 9 and 12 months for the 5 antipsychotics (typical-Haloperidol; atypical-Olanzapine, Amisulpride, Ziprasidone, Quetiapine). RESULTS: There are no statistically significant differences between groups treated with typical or atypical antipsychotics or between any individual antipsychotics concerning weight gain during the study. Weight gain was the highest in the first 3 months (57.49%) for all the studied neuroleptics. At the end of the study, the less increase was observed with ziprasidone (3.87 kg) and the highest with olanzapine (9.83 kg). CONCLUSION: Increase in weight has taken place for each individual neuroleptic, but also as a group (all neuroleptics) in the first three months (57.49%). Therefore, we should address the issue of weight gain with great care, especially in first period of antipsychotic administration, in order to fast deploy intervention tailored to maintain pre-treatment weight.

Vinorelbine-based chemotherapy in hormone-refractory prostate cancer.

BACKGROUND: No consensus exists regarding further therapy for the management of hormone-refractory prostate cancer. In this phase II study, the combination of Vinorelbine with 5-Fluorouracil and folinic acid (FLN regimen) was evaluated in patients with progressive or resistant disease after hormone therapy. PATIENTS AND METHODS: Thirty-four patients were treated with Vinorelbine at a dose of 20 mg/m2 intravenously (i.v.) on days 1 and 3, folinic acid (FA), 100 mg/m2 i.v. and 5-Fluorouracil (5-FU), 350 mg/m2 i.v. as a short infusion on days 1 to 3. The therapy was given in an out-patient setting, every 3 weeks. RESULTS: All of the 34 eligible patients were evaluable for toxicity and 30 for activity. A total of 127 cycles was administered (91% at full dose). Among thelS5 patients with measurable disease, four had a partial response (26.6%; C.I. 95%, 28.3% to 65.7%) and four achieved stable disease. In 14 patients (47%) a clinical benefit was documented. Six out of 15 patients with bone-only involvement had stable disease (40%). The median duration of stabilization and partial response was 16 weeks (range 4-24 weeks). The most common toxicity was hematological: Grade 4 (NCI-CTC scale) in five patients at re-cycle. Other toxicities were of low incidence and easy to manage. CONCLUSION: The encouraging results obtained with the FLN regimen in terms of clinical benefit and its predictable and manageable toxicity support the palliative role of this chemotherapeutic strategy in hormone-refractory prostate patients.

Near-infrared laser illumination transforms the fluorescence absorbing X-Gal reaction product BCI into a transparent, yet brightly fluorescent substance.

The beta-galactosidase protein generated by the bacterial LacZ gene is widely used to map gene expression patterns. The ease of its use is only rivaled by green fluorescent protein, which can be used in combination with various other procedures such as immunocytochemistry, flow cytometry, or tract tracing. The beta-galactosidase enzymatic reaction potentially provides a more sensitive assay of gene expression than green fluorescent protein. However, the virtual impermeability and tendency to absorb light over a wide range limit the use of the most frequently used beta-galactosidase substrate, X-Gal, in combination with other fluorescent labeling procedures. Here, we provide details on a simple photoactivation procedure that transforms the light-absorbing X-Gal product, 5-bromo-4-chloro-3-indolyl (BCI) precipitate, into an intensely fluorescent product excited by 488 and 633 nm light. Photoactivation is achieved through exposure to 730 nm near-infrared light emitted from a femtosecond titanium-doped Sapphire laser. Photoactivation of BCI occurs in tissue sections suspended in buffered saline, glycerol, or even embedded in epoxy resin. A protocol for the use of BCI photoactivation is here provided. Importantly, the BCI photoactivated product is photoswitchable, displaying bistable photochromism. This permits the use of the fluorescent product in a variety of co-localization studies in conjunction with other imaging modalities. As with other bistable and photoswitchable products, the BCI reaction product shows concentration quenching at high density and can be degraded by continuous exposure to intense 730 nm illumination. Therefore, care must be taken in developing imaging strategies. Our findings have implications for the use of X-Gal in gene and protein detection and provide a novel substrate for high density digital information storage.

Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit.

We investigated whether co-expression of Neurog 1 and Atoh 1 in common neurosensory precursors could explain the loss of hair cells in Neurog 1 null mice. Analysis of terminal mitosis, using BrdU, supports previous findings regarding timing of exit from cell cycle. Specifically, we show that cell cycle exit occurs in spiral sensory neurons in a base-to-apex progression followed by cell cycle exit of hair cells in the organ of Corti in an apex-to-base progression, with some overlap of cell cycle exit in the apex for both hair cells and spiral sensory neurons. Hair cells in Neurog 1 null mice show cell cycle exit in an apex-to-base progression about 1-2 days earlier. Atoh 1 is expressed in an apex-to-base progression rather then a base-to-apex progression as in wildtype littermates. We tested the possible expression of Atoh1 in neurosensory precursors using two Atoh 1-Cre lines. We show Atoh 1-Cre mediated beta-galactosidase expression in delaminating sensory neuron precursors as well as undifferentiated epithelial cells at E11 and E12.5. PCR analysis shows expression of Atoh 1 in the otocyst as early as E10.5, prior to any histology-based detection techniques. Combined, these data suggest that low levels of Atoh 1 exist much earlier in precursors of hair cells and sensory neurons, possibly including neurosensory precursors. Analysis of Atoh 1-Cre expression in E18.5 embryos and P31 mice reveal beta-galactosidase stain in all hair cells but also in vestibular and cochlear sensory neurons and some supporting cells. A similar expression of Atoh 1-LacZ exists in postnatal and adult vestibular and cochlear sensory neurons, and Atoh 1 expression in vestibular sensory neurons is confirmed with RT-PCR. We propose that the absence of NEUROG 1 protein leads to loss of sensory neuron formation through a phenotypic switch of cycling neurosensory precursors from sensory neuron to hair cell fate. Neurog 1 null mice show a truncation of clonal expansion of hair cell precursors through temporally altered terminal mitosis, thereby resulting in smaller sensory epithelia.

Atoh1 null mice show directed afferent fiber growth to undifferentiated ear sensory epithelia followed by incomplete fiber retention.

Inner ear hair cells have been suggested as attractors for growing afferent fibers, possibly through the release of the neurotrophin brain-derived neurotrophic factor (BDNF). Atoh1 null mice never fully differentiate hair cells and supporting cells and, therefore, may show aberrations in the growth and/or retention of their innervation. We investigated the distribution of cells positive for Atoh1- or Bdnf-mediated beta-galactosidase expression in Atoh1 null and Atoh1 heterozygotic mice and correlated the distribution of these cells with their innervation. Embryonic day (E) 18.5 Atoh1 null and heterozygotic littermates show Atoh1- and BDNF-beta-galactosidase-positive cells in comparable distributions in the canal cristae and the cochlea apex. Atoh1-beta-galactosidase-positive but only occasional Bdnf-beta-galactosidase-positive cells are found in the utricle, saccule, and cochlea base of Atoh1 null mutant mice. Absence of Bdnf-beta-galactosidase expression in the utricle and saccule of Atoh1 null mice is first noted at E12.5, a time when Atoh1-beta-galactosidase expression is also first detected in these epithelia. These data suggest that expression of Bdnf is dependent on ATOH1 protein in some but does not require ATOH1 protein in other inner ear cells. Overall, the undifferentiated Atoh1- and Bdnf-beta-galactosidase-positive cells show a distribution reminiscent of that in the six sensory epithelia in control mice, suggesting that ear patterning processes can form discrete patches of Atoh1 and Bdnf expression in the absence of ATOH1 protein. The almost normal growth of afferent and efferent fibers in younger embryos suggests that neither fully differentiated hair cells nor BDNF are necessary for the initial targeted growth of fibers. E18.5 Atoh1 null mice have many afferent fibers to the apex of the cochlea, the anterior and the posterior crista, all areas with numerous Bdnf-beta-galactosidase-positive cells. Few fibers remain to the saccule, utricle, and the base of the cochlea, all areas with few or no Bdnf-beta-galactosidase-positive cells. Thus, retention of fibers is possible with BDNF, even in the absence of differentiated hair cells.

Autopsy of an intradural haematoma case / Autosia de un caso de hematoma introdural

El autor describe la microscopia de la dura madre en un caso de hematoma intradural, y explica los criterios básicos de diagnóstico e un caso real de hematoma, con alcoholismo y trauma que produjo la muerte.

[The effect of cadmium on the gill structure in Tilapia]. / Vliianie kadmiia na strukturu zhabr tiliapii.

The effect of a long-term (2 months) exposure to cadmium (5 mg/l), with a subsequent recovery in clean water, upon gill structural organization of Mozambique tilapia was studied using scanning and light microscopy. Some of nonspecific components of the gill response on cadmium action were revealed: hypertrophy and fusion of respiratory lamellae, swelling and lifting of the epithelium from capillaries, vascular stasis. In addition, heavy metal-specific components of this reaction were found, which are involved in the development of epithelial necrosis and leucocyte infiltration into the tissue. The gill ultrastructure recovery was not achieved completely even after a 1.5 month exposure of fishes in clean water.

[Changes in the cellular ultrastructure of the gill epithelium in Tilapia under the action of cadmium on the fish]. / Izmenenie ul'trastruktury kletok zhabernogo épiteliia tiliapii pri deistvii na ryb kadmiia.

The ultrastructure of the Tilapia gill epithelium cells was studied under condition of a prolonged (2 months) treatment of these fishes with cadmium in a concentration of 5 mg/l. A decrease in the quantity of chloride cells in the primary gill epithelium, and of respiratory cells in the secondary epithelium was found. The chloride and mucous cells are, respectively, most sensitive and most resistant to the influence of cadmium. The accumulation of lysosomal structures in chloride and respiratory cells was observed, in addition to a reduced surface relief in these and some damage in mitochondria of the former being noticed. A slow development of reparation processes in the tilapia gill epithelium cells was followed after the cancellation of cadmium effect. No restoration of the original ultrastructural pattern of the gill epithelium cells was observed after a 1.5-month inhabitance of Tilapia in clean water.