Cocaine Augments Dopamine Mediated Inhibition of Neuronal Activity in the Dorsal Bed Nucleus of the Stria Terminalis.

The dorsal region of the bed nucleus of the stria terminalis (dBNST) receives substantial dopaminergic input which overlaps with norepinephrine input implicated in stress responses. Using ex vivo fast scan cyclic voltammetry in male C57BL6 mouse brain slices, we demonstrate that electrically stimulated dBNST catecholamine signals are of substantially lower magnitude and have slower uptake rates compared to caudate signals. Dopamine terminal autoreceptor activation inhibited roughly half of the catecholamine transient, and noradrenergic autoreceptor activation produced an ∼30% inhibition. Dopamine transporter blockade with either cocaine or GBR12909 significantly augmented catecholamine signal duration. We optogenetically targeted dopamine terminals in the dBNST of transgenic (TH:Cre) mice of either sex and, using ex vivo whole-cell electrophysiology, we demonstrate that optically stimulated dopamine release induces slow outward membrane currents and an associated hyperpolarization response in a subset of dBNST neurons. These cellular responses had a similar temporal profile to dopamine release, were significantly reduced by the D2/D3 receptor antagonist raclopride, and were potentiated by cocaine. Using in vivo fiber photometry in male C57BL6 mice during training sessions for cocaine conditioned place preference, we show that acute cocaine administration results in a significant inhibition of calcium transient activity in dBNST neurons compared to saline administration. These data provide evidence for a mechanism of dopamine-mediated cellular inhibition in the dBNST and demonstrate that cocaine augments this inhibition while also decreasing net activity in the dBNST in a drug reinforcement paradigm.SIGNIFICANCE STATEMENTThe dorsal bed nucleus of the stria terminalis (dBNST) is a region highly implicated in mediating stress responses, however, the dBNST also receives dopaminergic inputs from classically defined drug reward pathways. Here we used various techniques to demonstrate that dopamine signaling within the dorsal BNST region has inhibitory effects on population activity. We show that cocaine, an abused psychostimulant, augments both catecholamine release and dopamine-mediated cellular inhibition in this region. We also demonstrate that cocaine administration reduces population activity in the dBNST, in vivo Together these data support a mechanism of dopamine-mediated inhibition within the dBNST, providing a means by which drug-induced elevations in dopamine signaling may inhibit dBNST activity to promote drug reward.

Evaluation of 405-nm monochromatic light for inactivation of Tulane virus on blueberry surfaces.

AIM: The study aim was to evaluate the potential of 405-nm light as a virus intervention for blueberries. METHODS AND RESULTS: Tulane virus (TV)-inoculated blueberries were treated with 4·2 mW cm-2 of 405-nm light for 5-30 min. To mitigate thermal heating due to the intense light, a dry ice-chilled, nitrogen-based cooling system was utilized. Blueberries were rotated to ensure exposure of all surfaces to 405-nm light. Five-, 15- and 30-min treatments resulted in little or no inactivation of TV on blueberries (average log reductions of -0·18; -0·02; and +0·06 respectively). Since 405-nm light's inactivation mechanism may involve singlet oxygen, two singlet oxygen enhancers, riboflavin and rose bengal, were used to coat the blueberries prior to 405-nm light treatment. When 0·1% riboflavin or rose bengal was added, resulting in an average PFU reduction of -0·51 and -1·01 logs respectively. However, it was noted that the addition of riboflavin and rose bengal in the absence of 405-nm light treatment produced some inactivation. Average untreated log reductions for riboflavin and rose bengal were -0·13 and -0·66 respectively. Also, 60-30-s 405-nm light pulses with 2-min ambient cooling periods without the dry ice nitrogen cooling system did not inactivate TV, suggesting that oxygen limitation by the nitrogen CO2 mixture was not the cause of limited inactivation. CONCLUSIONS: Overall results indicate that 405-nm light has some potential to inactivate viruses if singlet oxygen enhancers are present. SIGNIFICANCE AND IMPACT OF THE STUDY: The potential of visible monochromatic violet/blue light (405 nm) as a nonthermal intervention for viruses on foods, such as berries that are prone to norovirus contamination, had not been previously evaluated. Use of food-grade singlet oxygen enhancer compounds in combination with visible spectra light may offer a means to inactivate foodborne viruses.

Aerodynamic implications of gull's drooped wing-tips.

When in gliding flight, gulls are observed to adopt a drooped wing-tip configuration. This paper investigates whether this configuration might represent an aerodynamic optimum or if it is the result of constraints imposed by the gull's anatomy. A computational model was developed for the aerodynamic performance of a gull in gliding flight. This model was used in conjunction with both global and local optimizers to determine the most aerodynamically optimal configuration for cases where the gull was constrained to move its wing within its natural flapping cycle as well as when the wing had full freedom of motion. The results of this analysis determined the best wing configuration for a gull in gliding flight and demonstrated that such a configuration not only had the highest lift-to-drag ratio but also could be achieved within the constraints of the kinematics of the gull wing. These results are of interest outside studies of gulls, since the drooped wing-tip configuration could be relevant for new designs of small air vehicles.

The physiologic role of alternative oxidase in Ustilago maydis.

Alternative oxidase (AOX) is a ubiquitous respiratory enzyme found in plants, fungi, protists and some bacterial species. One of the major questions about this enzyme is related to its metabolic role(s) in cellular physiology, due to its capacity to bypass the proton-pumping cytochrome pathway, and as a consequence it has great energy-wasting potential. In this study, the physiological role and regulatory mechanisms of AOX in the fungal phytopathogen Ustilago maydis were studied. We found evidence for at least two metabolic functions for AOX in this organism, as a major part of the oxidative stress-handling machinery, a well-described issue, and as part of the mechanisms that increase the metabolic plasticity of the cell, a role that might be valuable for organisms exposed to variations in temperature, nutrient source and availability, and biotic or abiotic factors that limit the activity of the cytochrome pathway. Experiments under different culture conditions of ecological significance for this organism revealed that AOX activity is modified by the growth stage of the culture, amino acid availability and growth temperature. In addition, nucleotide content, stimulation of AOX by AMP and respiratory rates obtained after inhibition of the cytochrome pathway showed that fungal/protist AOX is activated under low-energy conditions, in contrast to plant AOX, which is activated under high-energy conditions. An estimation of the contribution of AOX to cell respiration was performed by comparing the steady-state concentration of adenine nucleotides, the mitochondrial membrane potential, and the respiratory rate.

The effects of 5-HT on feeding behaviour in mianserin- or cyproheptadine-pretreated rats.

We examined the effects of 5-HT on the feeding behaviour patterns of rats pretreated with mianserin (5-HT(1B/2A/1D receptor antagonist) or cyproheptadine (a 5-HT(2c) receptor antagonist), injected into the pariventricular hypothalamus nucleus (PVN). The animals were kept at 21 +/- 1 degrees C with a 12 h light and 12 h dark cycle on a self-selected feeding paradigm, and provided with freely available and separate sources of proteins, carbohydrates, fats and water. The results indicate that the suppressive effect of 5-HT on carbohydrate intake can be blocked by mianserin and cyproheptadine even at the onset of the natural (dark) feeding period; however, this is a distinct blockade in the paradigm of feeding behavior. All of the meal patterns of fat intake and rest remained unaffected.

Effect of 5-HT in mianserin-pretreated rats on the structure of feeding behavior.

The present study examined the effects of intra-PVN serotonin injection in mianserin-pretreated rats at the onset of the dark phase of light cycle on the structure of feeding behavior. The drugs were injected into the paraventricular nucleus (PVN) of the hypothalamus. The animals were maintained in a self-selection feeding paradigm and provided with freely available and separate sources of protein, carbohydrate, fat and water. The suppressive effect of 5-HT on carbohydrate intake was attenuated by mianserin at the beginning of the active (dark) feeding period. Mianserin-pretreatment increased the duration of carbohydrate and protein intake, but it was unable to block the effect of 5-HT on meal frequency and local rate of carbohydrate consumption. The present data suggests that carbohydrate intake may be in part mediated by postsynaptic 5-HT(2A/2C) receptors. However, the temporal characteristics of carbohydrate ingestion are mediated by another subpopulation of 5-HT receptors in the PVN and indicates a possibly adrenergic influence.

Expression and localization of immunoreactive-sialomucin complex (Muc4) in salivary glands.

Sialomucin Complex (SMC; Muc4) is a heterodimeric glycoprotein consisting of two subunits, the mucin component ASGP-1 and the transmembrane subunit ASGP-2. Northern blot and immunoblot analyses demonstrated the presence of SMC/Muc4 in submaxillary, sublingual and parotid salivary glands of the rat. Immunocytochemical staining of SMC using monoclonal antisera raised against ASGP-2 and glycosylated ASGP-1 on paraffin-embedded sections of parotid, submaxillary and sublingual tissues was performed to examine the localization of the mucin in the major rat salivary glands. Histological and immunocytochemical staining of cell markers showed that the salivary glands consisted of varying numbers of serous and mucous acini which are drained by ducts. Parotid glands were composed almost entirely of serous acini, sublingual glands were mainly mucous in composition and a mixture of serous and mucous acini were present in submaxillary glands. Since immunoreactive (ir)-SMC was specifically localized to the serous cells, staining was most abundant in parotid glands, intermediate levels in submaxillary glands and least in sublingual glands. Ir-SMC in sublingual glands was localized to caps of cells around mucous acini, known as serous demilunes, which are also present in submaxillary glands. Immunocytochemical staining of SMC in human parotid glands was localized to epithelial cells of serous acini and ducts. However, the staining pattern of epithelial cells was heterogeneous, with ir-SMC present in some acinar and ductal epithelial cells but not in others. This report provides a map of normal ir-SMC/Muc4 distribution in parotid, submaxillary and sublingual glands which can be used for the study of SMC/Muc4 expression in salivary gland tumors.

Osteotomía periacetabular para el tratamiento de la displasia de cadera en adultos: resultados a corto plazo / Treatment of hip dysplasia in adults with periacetabular osteotomy

Entre agosto de 1997 y diciembre de 1998, se operaron 20 pacientes adultos con displasia acetabular residual sintomatica utilizando una osteotomia periacetabular tipo Oanz. El promedio de edad de los pacientes fue de 30.2 años (17-40 años) y el promedio de seguimiento fue de 11.6 meses (6-23 meses). El tiempo quirurgico promedio fue de 2.8 horas y el sangrado promedio fue de 873 cc. En todos los casos se obtuvo un cubrimiento acetabular anterior y lateral adecuado. En un paciente la corrección lograda se perdio en el postoperatorio debido a una fijaci6n insuriciente de la osteotomia y apoyo prematuro de la extremidad. En los 19 pacientes restantes se mantuvo corrección y los resultados clinicos utilizando la escala de Harris pre y postoperatorio fueron satisfactorios. Otras complicaciones importantes que se presentaron fueron: dolor neuropatico en dos pacientes y neuroapraxia del CPE en un paciente

Polyethylene wear and periprosthetic osteolysis in metal-backed acetabular components with cylindrical liners.

A retrospective clinical and radiographic analysis was performed in 27 hips (23 patients), in which a threaded, porous-coated acetabular component with cylindrical liner was implanted (Sintered T-Tab-ST cup, Biomet, Warsaw, IN). Sixteen hips had cemented stems; 11 had cementless, circumferentially porous-coated stems. The mean clinical and radiographic follow-up period was 68 months. The mean patient age was 49 years; the mean patient weight was 68 kg. The mean rates of linear and volumetric wear were 0.25 mm/y and 149 mm3/y, respectively. Osteolysis occurred in 51.8% (14 hips). Wear rate and young age correlated with osteolysis (P = .0002 and P = .01, respectively). There were no cases of distal femoral osteolysis.

Photodynamic therapy of rat endometrium sensitized with tin ethyl etiopurpurin.

STUDY OBJECTIVE: To evaluate endometrial ablation in the rat using photodynamic therapy and the photosensitizer tin ethyl etiopurpurin (SnET2). DESIGN: Laboratory research. SETTING: A pharmaceutical and device manufacturing company. MATERIALS: Forty-five healthy female rats (age 8-10 wks). INTERVENTIONS: Groups of three to five rats were given SnET2 by either intrauterine or intravenous administration. Light treatment was given at either 3 or 24 hours after SnET2 administration at a light dose of 75, 150, or 200 J/cm. MEASUREMENTS AND MAIN RESULTS: A fluorescence detection system was employed to determine relative drug uptake of SnET2 into uterine tissue. The highest levels of SnET2 were detected at 3 hours. After light treatment, responses of uterine tissues were evaluated histologically. The best endometrial ablation was seen when SnET2 was given by intrauterine administration with light treatment at 150 J/cm 24 hours later. A consistent transmural response was seen with this route of administration at 200 J/cm. Intravenous SnET2 gave inconsistent responses. In light-only controls, all light doses caused no tissue response. The depth of necrosis in tissues treated with photodynamic therapy were light-dose dependent. CONCLUSION: With either route of SnET2 administration, drug uptake was confirmed and a light-dose-dependent response in the walls of rat uterine horns was demonstrated.

Drosophila melanogaster syncytial nuclear divisions are patterned: time-lapse images, hypothesis and computational evidence.

Time-lapse microscopy of biological systems has provided new and exciting information about the dynamics of cellular and developmental events. However, these events are often complex and difficult to analyze. This paper describes a study in which computation was indispensable for formulating and evaluating a cellular/developmental hypothesis directly from observations of time-lapse fluorescence images. Previous analyses of time-lapse microscopy sequences of Drosophila melanogaster embryonic syncytial nuclear cycles 10-13, when the nuclei form an evenly spaced monolayer at the surface of the embryo, have failed to identify any pattern in these divisions. However, computational analysis of the data has provided evidence that the direction of syncytial nuclear mitosis is not random, but is clearly influenced by the relative positions of neighboring nuclei. An approximate law governing mitotic direction that is based on a scheme that compromises among "votes" made by neighboring nuclei is introduced.

[Massive paracentesis and administration of dextran 70 vs albumin in cirrhotic patients with tense ascites]. / Paracentesis masiva con reposición de dextran 70 vs albúmina en pacientes cirróticos con ascitis a tensión.

Some studies have demonstrated that paracentesis for large-volume extraction of ascites produces renal failure and hyponatremia, and intravenous infusion of plasma expanders can overcome this complications. We performed a survey where we compared effectiveness of dextran 70 vs albumin on prevention of adverse effects and cost differences. Two random groups were formed, 8 cirrhotic patients with tense ascites in each group. Paracentesis with extraction of more than 5 liters was performed. The group A received human albumin and group B dextran 70, both received 6 g per liter of extracted liquid. 24 hours before and 48 hours after of ascites extraction, we performed hepatic function test, blood chemistry with renin and aldosterone. Clinical results and biochemistry test were similar in both groups without statistical significance (p > 0.05). Amount of plasma expander was almost the same, but the cost in group A was $266 USD and in group B $20.8 USD. Azotemia was present in 12.5% in group A and hyponatremia in 12.5% in both groups, without symptoms. The results show that dextran 70 produces the same effect like albumin in the treatment of ascites after large-volume paracentesis with lower cost.

[The seroprevalence of antibodies against the hepatitis C virus in blood donors at the Hospital Central Militar]. / Seroprevalencia de anticuerpos contra el virus de la hepatitis C en donadores de sangre del Hospital Central Militar.

The main transmission mechanism for hepatitis C virus is through blood products. In order to know seroprevalence of antibodies in military personnel, 2,564 samples at the Central Military Hospital with a second generation Enzymatic Immunoassay (EIA-2) were studied. All participants were males; the mean age was 25 years (range 17-47). Positive results were found in 19 potential donors (0.74%); similar seroprevalences have been reported by others. Patient selection helps to improve the safety of transfusions.

[The transjugular intrahepatic portosystemic stent-shunt (TIPS) in the management of portal hypertension. A preliminary report]. / Fístula portosistémica con prótesis intrahepática por vía transyugular (TIPS) en el manejo de la hipertensión porta. Communicación preliminar.

Transjugular intrahepatic portosystemic shunt-stent (TIPS) was performed in 5 patients with cirrhosis and portal hypertension. Bleeding varices occurred in 4 patients and refractory ascites in one. We used 2 Wallstents and 3 Strecker stents. Shunt patency, recurrent variceal hemorrhage and ascites were evaluated. The shunts were created from a transjugular approach between the hepatic and portal vein, with diameters of 10 mm. Portal pressure was adequately decreased in all cases. The hospital stay, following TIPS was 3 days. Complete variceal decompression was identified endoscopically in 3 patients, and partial in one. Four shunts were patent by ultrasound and color Doppler at 1 to 6 months of follow up. One patient presented encephalopathy and one died at third day after TIPS. Initial results suggest that TIPS is an effective method of portal decompression for treatment of variceal hemorrhage and refractory ascites. The main complication was encephalopathy and only one patient died.

Primary antiphospholipid syndrome with multiorgan arterial and venous thromboses.

A 57-year-old man with no evidence of infection, vasculitis or connective tissue disease died with multiple organ thromboses after an acute illness. He was found to have lupus anticoagulant, IgG anticardiolipin antibody, false positive rapid plasma reagin, prolonged partial thromboplastin time, and thrombocytopenia. Venous and arterial thrombi leading to necrosis were found in his scrotum, testicles, upper and lower extremities, adrenals, kidneys, lungs, and brain. No other explanation could be found for his fatal illness, thus suggesting the primary antiphospholipid syndrome (APS). This is a documented case of primary APS associated with multiorgan arterial and venous thromboses of large and small vessels, presenting as a fulminant and fatal acute illness.

Pseudallescheria boydii brain abscess. Complication of an intravenous catheter.

An adult patient survived a brain abscess with Pseudallescheria boydii. She received intraventricular miconazole, 20 mg every 72 hours (minimal inhibitory concentration = 0.4 microgram/ml), and surgery. The abscess resulted from an infected central venous catheter (Port-A-Cath) and steroid therapy. Miconazole caused a ventriculitis. There are 12 reported cases of P. boydii brain abscesses from 1965 to 1985 with only two survivors.

Hepatitis B in obstetric patients in the community hospital: the need for screening.

A prospective survey was conducted in a 200-bed community hospital that averages approximately 250 deliveries per month. One hundred consenting obstetric patients were screened for hepatitis B surface antigen (HBsAg). Additionally, hospital physicians were encouraged to order an entire hepatitis serological profile on high-risk obstetric patients, as defined by the Centers for Disease Control; six additional patients were screened by these physicians. Of the 106 patients screened, two (1.9%) were found to have HBsAg. Both were among the six high-risk patients, indicating a 33% prevalence of HBsAg among high-risk obstetric patients and a zero prevalence among low-risk patients. The results appear to support the need for screening of high-risk obstetric patients for hepatitis B. Moreover, vaccination against hepatitis B is advisable for obstetric health-care personnel, who are frequently exposed to blood and extravascular fluids.

Endocarditis with Moraxella-like M-6 after cardiac catheterization.

A patient developed bacteremia with CDC group M-6, a Moraxella-like bacterium, after a complicated heart catheterization. He was treated with tobramycin and ampicillin. The aortic valve was later replaced and did not show any signs of infection. The slow growth of M-6 can delay diagnosis and give misleading antibiotic susceptibility results. Penicillin is not always active against this organism.

Defective monocyte chemotaxis in mycosis fungoides: lack of essential helper lymphocytes.

The effect of lymphocytes on monocytes chemotaxis in vitro was studied using lymphocyte fractions prepared by glass bead column separation and mononuclear cell fractions prepared by Ficoll-Hypaque separation. The diminished monocyte chemotaxis in ten patients with mycosis fungoides was corrected in vitro by the addition of normal lymphocytes. This helper effect was not mediated by soluble factors. Lymphocytes from mycosis fungoides patients did not inhibit chemotaxis by monocytes from mycosis fungoides patients did not inhibit chemotaxis by monocytes from normal donors. No cell directed chemotactic inhibitor, differences in LDCF production in vitro or differences in circulating chemattractants were found. These data support the conclusion that the abnormal monocyte chemotaxis seen in mycosis fungoides is due to lack of essential helper lymphocyte function and represents an abnormal mononuclear cell interaction which may be important in the establishment of the mononuclear cell infiltrate in mycosis fungoides.