[DSM-5--what has changed in therapy for and research on substance-related and addictive disorders?]. / DSM-5--Was ändert sich für die Suchttherapie und -forschung?

The new edition of the DSM, which was published in May of 2013, has brought the following changes in the now called category "substance-related and addictive disorders". The terms dependency and misuse or abuse will be replaced by the terminus "substance use disorder". There is a moderate substance use disorder, if two or three criterias are fulfilled for a period of 12 months. To speak of a severe substance use disorder, it has to be four or more criteria for the duration of 12 months. Furthermore, pathological gambling will be a part of the DSM-5 as a non-substance use disorder, but rather an addictive disorder. It is possible, that internet addiction will be a part of a revised version in DSM-5 for addictive disorders. The now changed criteria will have consequences on diagnosis, therapy and research concerning substance-related and addictive disorders. The leading diagnosis standards DSM-5 and ICD-10 or the following ICD-11 will continue to drift further apart from each other.

Zooplankton communities and their relationship with water quality in eight reservoirs from the midwestern and southeastern regions of Brazil.

Zooplankton are widely recognised as being regulated primarily by predators and food availability. In reservoirs, the quantity and quality of food resources are generally affected by the characteristics of the water, which in turn are controlled by the flow pulse generated by operation of the dams. In this study, we investigated the relationship between zooplankton, water quality and food availability (phytoplankton) in eight hydroelectric reservoirs located in Brazil. Samples were collected during the rainy and dry periods between 2008 and 2009. In general, the reservoirs exhibited mesotrophic conditions and Cyanobacteria were the predominant phytoplankton. The results showed that the rotifers Kellicottia bostoniensis, Hexarthra mira, Keratella spp., and Polyarthra vulgaris were present, indicating nutrient-rich environments. In addition, the copepod Thermocyclops decipiens occurred in eutrophic environments. In contrast, the cladoceran Daphnia gessneri and copepod Notodiaptomus henseni were considered indicators of more desirable water quality, owing to their relationship with waters with lower levels of nutrients and suspended solids. The results support the use of these organisms as a useful tool for understanding changes in water quality and in the ecosystem processes involved.

Illusory contours and cortical neuron responses.

Figures in which human observers perceive "illusory contours" were found to evoke responses in cells of area 18 in the visual cortex of alert monkeys. The cells responded as if the contours were formed by real lines or edges. Modifications that weakened the perception of contours also reduced the neuronal responses. In contrast, cells in area 17 were apparently unable to "see" these contours.

Development of stereopsis and cortical binocularity in human infants: electrophysiological evidence.

Dynamic random-dot stereograms and correlograms were used to elicit visually evoked brain potentials from human infants, and these potentials were compared with potentials evoked by classical checkerboard pattern reversal. The results indicate that infants begin to produce stereoscopically evoked potentials at the age of 10 to 19 weeks, several weeks after showing classical checkerboard-evoked potentials, and suggest that the onset of cortical binocularity precedes stereopsis.

Coincidence of a ductal pancreatic cyst and a gastric duplication cyst: a case report.

We report a case of two abdominal cystic formations in an 18-month-old girl. Laparotomy was performed with surgical removal of both cysts. The cysts were connected by a fibrous bridge. Histology revealed a gastric duplication cyst and a ductal pancreatic cyst originating from an aberrant pancreatic lobe. No fistula was found either to the alimentary tract or in either of the cysts. The clinical picture and treatment are described and compared to findings in the literature.

Spatial and temporal variations in fish assemblage: testing the zonation concept in small reservoirs.

Large reservoirs usually present spatial gradients in fish assemblage, distinguishing three strata (littoral, pelagic, and bathypelagic) along the vertical and horizontal axes, and three zones (fluvial, transitional, and lacustrine) along the longitudinal axis. The main objective of this study was to assess if small reservoirs also present the spatial gradients in fish assemblage attributes and structure as already observed in large reservoirs. Fish surveys were conducted quarterly, from 2003 to 2008, in the Mourão Reservoir (Mourão River, Paraná, Brazil), using gillnets with different mesh sizes, arranged in all strata of all three zones. Community attributes (species richness and evenness) were calculated for each sample, and differences were tested using three-way ANOVA (factors: zone, strata, year). Community composition was summarized using Correspondence Analysis (CA) and differences were tested with three-way ANOVA for each axis, controlling the same three factors. Because of the high variability in reservoir water level through time, all analyses were made considering temporal variations. Species richness presented a decreasing trend from fluvial to lacustrine zones, and higher values in littoral strata, possibly because upper reaches and littoral regions provide better conditions for fish to feed and to reproduce. Evenness was considerably low, presenting high variability, and no evident pattern. The expected longitudinal gradient was not found in this study indicating longitudinal similarity, contrary to observed in large reservoirs. Vertical and horizontal gradients were observed in all sampling stations, indicating that abiotic and biotic conditions are influencing fish distributions within the reservoir.

Host-parasite relationships of monogeneans in gills of Astyanax altiparanae and Rhamdia quelen of the São Francisco Verdadeiro River, Brazil.

This study investigates the ecology of monogenean gill parasites of Aslyanax altiparanae Garutti & Britski, 2000 and Rhamdia quelen (Quoy & Gaimard, 1824) in a stretch of the Sao Francisco Verdadeiro River, Parana, Brazil. Statistical and ecological indices were used to examine observed levels of parasitism in relation to host and environmental characteristics. A. altiparance and R. quelen had infestation intensities of 2.8 and 23.1 parasites per fish, respectively. The only significant environmental influence was observed at the upstream station for R. quelen. For both host species, parasitized and non-parasitized individuals presented similar weight-ength relationships. Parasitized individuals had dispersed K,, values indicating abnormal conditions. The low levels of parasitism observed in this study suggest that the environment is relatively undisturbed. Additional studies should compare these two species and their respective parasites following completion of the hydroelectric headquarters planned for construction in this stretch of the Sao Francisco Verdoadeiro River.

Zooplankton communities and their relationship with water quality in eight reservoirs from the midwestern and southeastern regions of Brazil / Comunidades de zooplâncton e sua relação com a qualidade da água em oito reservatórios das regiões Centro-Oeste e Sudeste do Brasil

Abstract Zooplankton are widely recognised as being regulated primarily by predators and food availability. In reservoirs, the quantity and quality of food resources are generally affected by the characteristics of the water, which in turn are controlled by the flow pulse generated by operation of the dams. In this study, we investigated the relationship between zooplankton, water quality and food availability (phytoplankton) in eight hydroelectric reservoirs located in Brazil. Samples were collected during the rainy and dry periods between 2008 and 2009. In general, the reservoirs exhibited mesotrophic conditions and Cyanobacteria were the predominant phytoplankton. The results showed that the rotifers Kellicottia bostoniensis, Hexarthra mira, Keratella spp., and Polyarthra vulgaris were present, indicating nutrient-rich environments. In addition, the copepod Thermocyclops decipiens occurred in eutrophic environments. In contrast, the cladoceran Daphnia gessneri and copepod Notodiaptomus henseni were considered indicators of more desirable water quality, owing to their relationship with waters with lower levels of nutrients and suspended solids. The results support the use of these organisms as a useful tool for understanding changes in water quality and in the ecosystem processes involved.

Resumo O zooplâncton é amplamente reconhecido como sendo regulado principalmente por predadores e pela disponibilidade de alimento. Em reservatórios, a quantidade e a qualidade de recursos alimentares são afetadas pelas características da água que, por sua vez, são controladas pelo pulso de fluxo gerado pela operação das barragens. Neste estudo, investigamos a relação entre o zooplâncton, qualidade d'água e a disponibilidade de alimento (fitoplâncton) em oito reservatórios hidrelétricos localizados no Brasil. Amostras foram coletadas durante os períodos chuvoso e seco, entre os anos de 2008 e 2009. Em geral, os reservatórios exibiram condições mesotróficas e Cyanobacteria foi o fitoplâncton predominante. Os resultados mostraram que os rotíferos Kellicottia bostoniensis, Hexarthra mira, Keratella spp. e Polyarthra vulgaris foram indicadores de ambientes ricos em nutrientes. Além disso, o copépode Thermocyclops decipiens ocorreu em ambientes eutróficos. Por outro lado, o cladócero Daphnia gessneri e o copépode Notodiaptomus henseni foram considerados indicadores de melhor qualidade da água, devido a sua relação com águas com baixos níveis de nutrientes e sólidos em suspensão. Os resultados suportam o uso desses organismos como uma ferramenta útil para o entendimento das mudanças na qualidade d'água e nos processos ecossistêmicos envolvidos.

Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome.

To our knowledge, this is the first reported comparison of clonidine with benzodiazepine in the management of acute alcohol withdrawal syndrome. In a double-blind trial, 61 men experiencing acute alcohol withdrawal were randomly assigned to receive clonidine or chlordiazepoxide over a 60-hour treatment period. Clonidine was more effective than chlordiazepoxide at reducing alcohol withdrawal scale scores, systolic blood pressures, and heart rates over the entire study period. Clonidine was as good as chlordiazepoxide at improving Cognitive Capacity Screening Exam, Hamilton Anxiety Rating Scale, and Self-Rating Scale scores. Adverse drug reactions reported by each group were similar, though less nausea and vomiting were observed in the clonidine group. Clonidine may represent a new alternative agent for the management of acute alcohol withdrawal syndrome.

In situ identification of lymphoreticular cells in benign and malignant infiltrates by membrane receptor sites.

Immunologic membrane markers have been utilized for the in situ identification of lymphoreticular cells within lymphoreticular tissues and in inflammatory and neoplastic lymphoreticular infiltrates of the skin. Frozen sections were layered with untreated sheep red blood cells (SRBC) for the detection of the E receptor on T cells, SRBC coated with 7S antibody for the detection of the Fc receptor (IgGEA) and SRBC coated with 19S antibody and complement (IgMEAC) for the detection of the C3 receptor. In normal lymphoreticular tissue, IgGEA selectively bound to areas colonized by macrophages, IgMEAC to B-dependent areas, whereas E showed no adherence. In chronic lymphatic leukemia, a predominant and selective adherence of IgMEAC was found in lymphoreticular organs which supports the B-cell nature of the neoplastic cells; in leukemic reticuloendotheliosis a selective IgMEAC adherence was observed and this favors a monocytoid origin of the hairy cells. Adherence of any indicator cell was practically absent from skin infiltrates of mycosis fungoides, which represents an additional piece of evidence for the T-cell nature of this disease process. In psoriasis, a considerable binding of IgGEA was observed, whereas IgMEAC did not adhere at all. This result indicates that the lymphocytic part of the infiltrate in this disease consists mainly of T cells.

Parathyroid hormone-related protein and life expectancy in hypercalcemic cancer patients.

We determined the effect of raised serum levels of midregional (53-84) parathyroid hormone-related protein (PTHrP) on life expectancy in 59 cancer patients with first presentation of hypercalcemia. The patients were stratified according to the serum PTHrP levels measured on day 0 after fluid repletion prior to bisphosphonate therapy. Twenty-nine patients were assigned to group N (PTHrP < or = 21 pmol/L) and 30 to group E (PTHrP > 21 pmol/L). Breast cancers were more common in group N, squamous cell cancers predominated in group E (p < 0.02). More patients with normal PTHrP had skeletal metastases, whereas group E was characterized by a higher incidence of prognostically unfavorable visceral involvement (p < 0.001). Bisphosphonates (pamidronate or BM.210955) were administered on day 0. Within one week, normocalcemia (serum calcium < or = 2.6 mmol/L) was restored in 96% of patients in group N, compared to 70% of patients in group E (p < 0.01). On day 12, 7 patients with elevated PTHrP were still hypercalcemic. Although a comparable number of patients in the two groups received cytostatic treatment after day 12, objective tumor responses were seen only in group N (n = 6; p < 0.05). Calculated from the first occurrence of hypercalcemia, the median survival was 66 days in group N and 33 days in group E (log-rank test: p = 0.0456; Wilcoxon-Breslow test: p = 0.0475). We conclude that in hypercalcemia of malignancy raised serum levels of PTHrP indicate a reduced hypocalcemic response to bisphosphonates, a more advanced tumor state and, therefore, an extremely poor prognosis.

The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease.

Bone metastases strongly affect skeletal metabolism by both their growth and their paracrine activities. However, so far no specific laboratory marker has been found to signal the spread of neoplastic disease to bone. We performed a cross-sectional study of 153 cancer patients and an equal number of healthy controls matched for sex and age, in which we determined serum levels of calcium and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic validity of the biochemical parameters measured with regard to neoplastic bone involvement. In the cancer group, 98 patients had overt bone metastases, as judged from radiographic and radioisotopic bone imaging. The remaining 55 patients were also in an advanced stage of disease, but there was no evidence of malignant bone involvement. In comparison to healthy controls, patients both with and without metastatic bone disease had significantly higher levels of TAP, uPYD, and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the median serum calcium level higher than in the healthy controls (P < 0.02). uCa was the same in cancer patients and the control group. Within the collective of cancer patients, individuals with skeletal metastases had higher levels of serum calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than patients without evidence of malignant bone disease. uCa did not differ between the 2 groups of cancer patients. The cancer patients were then stratified into 4 subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the absence or evidence of bone metastases. This stratification revealed that in patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels significantly exceeded those in normocalcemic patients. When the efficacy of TAP, uCa, uPYD, and uDPD in discriminating between patients with and without bone metastases was evaluated by use of receiver-operating characteristic curves and stepwise multivariate regression analysis, uPYD was found to have the highest diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547-12.306).(ABSTRACT TRUNCATED AT 400 WORDS)

Brain tumors: detection of B-cell stimulatory factor-2/interleukin-6 in the absence of oligoclonal bands of immunoglobulins.

24 patients with neoplasia of the central nervous system (CNS-N) were investigated for the presence of B-cell stimulatory factor-2/interleukin-6 (IL-6) in the cerebrospinal fluid (CSF). Whereas IL-6 was detected in 21 (88%) of these CSF samples, only 6% of CSF from non-inflammatory brain diseases and 12% of the samples from multiple sclerosis patients were positive. IL-6 was found in both primary and secondary CNS-N. The presence of IL-6, a cytokine which activates B-lymphocytes to produce high-rate immunoglobulin (Ig) synthesis, is in contrast to the ineffective intrathecal B-cell activation as suggested by the failure to detect oligoclonal bands of Igs in CNS-N.

Effect of clodronate treatment on bone scintigraphy in metastatic breast cancer.

Because of their high affinity for bone, bisphosphonates are used both in the treatment of benign and malignant bone disease and in radiopharmaceutical bone imaging. A prospective study was undertaken to evaluate whether intravenous clodronate (dichloromethylene bisphosphonate) therapy might affect the results of bone scintigraphy with 99mTc-labeled methylene diphosphonate (MDP). In 11 female patients with breast cancer and metastatic bone disease, quantitative bone scans were obtained using a region of interest (ROI) method on Days 0 and 22. After intravenous clodronate therapy from Day 1 to Day 21, all metastatic bone lesions were still detectable, and median ROI ratios did not differ to a statistically significant extent from baseline values. Serum calcium levels decreased (p = 0.0449), whereas parathyroid hormone concentrations showed an increase (p = 0.0053). Mean serum levels of creatinine, inorganic phosphorus, osteocalcin, gamma glutaminyl-transpeptidase and alkaline phosphatase remained unchanged. However, a more than twofold rise in the serum activity of alkaline phosphatase was measured in three patients. We conclude that 3 wk of intravenous clodronate treatment did not impair the sensitivity of 99mTc-MDP bone scintigraphy in detecting bone lesions in patients with metastatic breast cancer.

Effects of chemotherapeutic agents on expression of somatostatin receptors in pancreatic tumor cells.

UNLABELLED: Specific tumors express high amounts of receptors for somatostatin (SST), providing the basis for imaging and treatment using radiolabeled SST analogs. However, little is known about the potential influence of cytotoxic drugs on SST receptor (SSTR) expression in malignant cells. METHODS: To study the interaction between cytotoxic drugs and SSTR expression, the pancreatic cancer-derived tumor cell lines BxPC-3, Panc-1, Capan-1, and ASPC-1 were exposed to a range of cytotoxic drugs in vitro: Gemcitabine, 5-fluorouracil, cisplatin (cis-diaminedichloroplatinum [II]), camptothecin, mitomycin C, and doxorubicin were checked for changes in binding characteristics of the SSTR ligand (111)In-1,4,7,10-tetraazacyclododecane- N,N',N",N"'-tetraacetic acid-lanreotide (DOTA-LAN). Chemosensitivity was quantitated by measurements of reduction in cell numbers, changes in cell cycle distribution, and appearance of apoptotic subG1 (subG1/0 cell DNA content) cells. RESULTS: Cells were treated with gemcitabine (1.0 or 2.0 microg/mL), 5-fluorouracil (65-520 microg/mL), camptothecin (1.5 or 3 microg/mL), mitomycin C (0.1 or 0.2 microg/mL), and doxorubicin (1.0 or 2.0 microg/mL). Each of the chemotherapeutic agents induced a loss of high-affinity receptors. In addition, gemcitabine caused a reduction of low-affinity receptors in BxPC-3, Panc-1, and ASPC-1 cells. Mitomycin C, camptothecin, and 5-fluorouracil also induced an overexpression of low-affinity receptors. In cells pretreated with cisplatin (2-10 microg/mL), binding of DOTA-LAN was increased. Excluding gemcitabine, the increase in low-affinity binding sites exhibits a weak correlation with apoptosis (r(2) = 0.62). For gemcitabine, these effects were reversed after 4 d of recovery of the cell lines, eventually revealing overexpression of low- and high-affinity sites for BxPC-3 and Panc-1 cells and low-affinity sites for ASPC-1 cells. CONCLUSION: Our results clearly show that the pancreatic tumor lines reduce the expression of high-affinity DOTA-LAN binding sites during application of chemotherapeutic drugs, which is accompanied by variable overexpression of low-affinity binding sites. In the case of gemcitabine, SSTRs are overexpressed during recovery from drug exposure within 4 d. These findings may have implications on the interpretation of scintigraphic results obtained by receptor ligands.

The impact of extracellular matrix on the chemoresistance of solid tumors--experimental and clinical results of hyaluronidase as additive to cytostatic chemotherapy.

Chemoresistance is of outstanding importance for the limited results of chemotherapy in solid tumors. Chemoresistance of multicellular tumor tissues is more pronounced than that of single cells in vivo and in vitro. The enzyme hyaluronidase is able to loosen the cell-cell contact and the interstitial connective tissue and as such, in a number of preclinical and clinical trials, was shown to enhance the efficacy of cytostatic agents. Although proven to be very effective as additive to local chemotherapy, the systemic efficacy is not documented as well. We present a randomized trial done in high-grade astrocytomas with combined chemotherapy and radiation therapy with and without hyaluronidase. After very promising pilot results with systemic hyaluronidase in various tumor entities and also astrocytomas, this randomized study failed to show synergy to chemotherapy and radiation therapy in high-grade astrocytomas concerning survival. The promising preclinical data and the rather well documented activity in therapeutic use as additive to local chemotherapy seem to be an adequate motive to further elucidate the complex manner in which hyaluronidase is active in the interstitial tumor matrix and to obtain more information concerning the optimal route of application, the optimal dosage and the spectrum of tumor entities where it is synergistic with cytostatic chemotherapy and perhaps even radiation therapy.

The differentiation inducers phenylacetate and phenylbutyrate modulate camptothecin sensitivity in colon carcinoma cells in vitro by intracellular acidification.

Aromatic fatty acids such as phenylbutyrate (PB) and its metabolite phenylacetate (PA) induce growth arrest, differentiation and apoptosis in solid tumor cells. Despite their antiproliferative action they were reported to exhibit a synergistic effect in combination with cytotoxic drugs like topotecan, and others. Since the activity of the camptothecines (CPTs) depends on local pH conditions, we investigated, whether PB/PA modulate CPT effects indirectly by affecting intracellular pH in SW620 and SW480 colon cancer cells. The results for the colon carcinoma cells show an antagonistic interaction for the combination of CPT and 0.25-5 mM PA in viability assays, resulting in an approximately 3-fold increase in IC50 (control: 20+/-7 nM). A synergistic effect with significantly increased numbers of late apoptotic/necrotic cancer cells (difference +21+/-4%) and 1.4-fold sensitization were detected upon inclusion of 2.5 mM PA during a 4-h CPT (10 micro;M) loading phase. In response to 0.25-1 mM PA/PB the cells exhibit a reversible decrease of pHi (0.1-0.31 pH units) in HEPES- or bicarbonate-buffered media. Dose-dependent acidification and pHi-recovery occurred following addition of PA and PB after an acid load and inhibition of the Na+/H+-antiporter and bicarbonate exchangers, pointing to a possible intracellular mechanism of cytoplasmic acidification. It is concluded that the synergistic modulation of CPT toxicity by short-term PA/PB treatment in colon carcinoma cells is caused by changes in intracellular pH, possibly affecting quantity and localization of the active closed lactone form of this drug.

In vitro antitumor activity of MIC2 protein-doxorubicin conjugates.

The pseudoautosomal encoded MIC2 glycoprotein is a tumor-associated antigen of Ewing's sarcoma (ES) and closely related tumors of unknown function. To investigate the use of this protein as selective drug carrier recombinant MIC2 was coupled to doxorubicin by a two step glutaraldehyde method (molar ratio DOX/MIC2 of 32 and 16). The conjugates showed dose-dependent cytostatic activity against the ES cell line SK-ES1, the peripheral neuroectodermal line KAL and the prostate cancer cell line PC-3 concurrent with reduced toxicity against normal lymphoblasts. In comparison to free doxorubicin the MIC2-doxorubicin conjugates exhibited highest activity against the PC-3 cell line. Confocal microscopy showed intracellular accumulation of MIC2 conjugates.

Resveratrol pretreatment desensitizes AHTO-7 human osteoblasts to growth stimulation in response to carcinoma cell supernatants.

Resveratrol, a natural phytoestrogen, has been reported to promote differentiation of murine MC3T3-E1 osteoblasts and to inhibit proliferation of prostate cancer cell lines. In the present study we tested the effects of resveratrol on the increased proliferation of human AHTO-7 osteoblastic cell line induced by conditioned media (CM) from a panel of carcinoma cell lines. This compound was found to modulate AHTO-7 proliferation in a tamoxifen-sensitive mechanism at lower concentrations, but failed to induce the osteoblast differentiation marker alkaline phosphatase (ALP) in contrast to vitamin D3. The proliferative response of AHTO-7 cells to conditioned media from carcinoma cell lines was diminished (30-71.4% inhibition) upon pretreatment with 0.5 microM resveratrol. Highest inhibition was demonstrated for pancreas (BxPC3, Panc-1), breast (ZR75-1) and renal (ACHN) carcinoma cell line supernatants whereas the effect on colon carcinoma (SW620, Colo320DM) cell CM and prostate cancer (PC3, DU145 and LNCaP) CM was less pronounced. Direct addition of resveratrol affected only supernatants of cell lines (<25% inhibition) exhibiting growth stimulatory activity for normal WI-38 lung fibroblasts. Resveratrol inhibited proliferation of DU145 and LNCaP cells in concentrations exceeding 5 microM, altered cell cycle distribution of all prostate cancer cell lines in concentrations as low as 0.5 microM, but did not inhibit the production of osteoblastic factors by these lines. In conclusion, resveratrol failed to induce ALP activity as marker of osteoblast differentiation in human osteoblastic AHTO-7 cells, however, inhibited their response to osteoblastic carcinoma-derived growth factors in concentrations significantly lower than those to reduce growth of cancer cells, thus effectively modulating tumor - osteoblast interaction.

Transitional cell carcinoma of ileal loop following cystectomy.

This is the second case reported in the literature involving transitional cell carcinoma in an ileal loop. The case is described and the literature reviewed.