Photoactive High Explosives: Substituents Effects on Tetrazine Photochemistry and Photophysics.

High explosives that are photoactive, i.e., can be initiated with light, offer significant advantages in reduced potential for accidental electrical initiation. We examined a series of structurally related tetrazine based photoactive high explosive materials to detail their photochemical and photophysical properties. Using photobleaching infrared absorption, we determined quantum yields of photochemistry for nanosecond pulsed excitation at 355 and 532 nm. Changes in mass spectrometry during laser irradiation in vacuum measured the evolution of gaseous products. Fluorescence spectra, quantum yields, and lifetimes were measured to observe radiative channels of energy decay that compete with photochemistry. For the 6 materials studied, quantum yields of photochemistry ranged from <10(-5) to 0.03 and quantum yield of fluorescence ranged from <10(-3) to 0.33. In all cases, the photoexcitation nonradiatively relaxed primarily to heat, appropriate for supporting photothermal initiation processes. The photochemistry observed was dominated by ring scission of the tetrazine, but there was evidence of more extensive multistep reactions as well.

Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators.

BACKGROUND AND PURPOSE: Medical and neurological complications after acute ischemic stroke may adversely impact outcome and in some cases may be preventable. Limited data exist regarding the frequency of such complications occurring in the first days after the ictus and the relationship of these complications to outcome. Our objective was to identify the types, severity, and frequency of medical and neurological complications following acute ischemic stroke and to determine their role in mortality and functional outcome. METHODS: Rates of serious (life-threatening) and nonserious medical and neurological complications and mortality were derived from the placebo limb of the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS) database (n=279). Complications were correlated with clinical outcome using logistic regression techniques. RESULTS: Of all patients, 95% had at least one complication. The most common serious medical complication was pneumonia (5%), and the most common serious neurological complication was new cerebral infarction or extension of the admission infarction (5%). The 3-month mortality was 14%; 51% of these deaths were attributed primarily to medical complications. Outcome was significantly worse in patients with serious medical complications, after adjustment for baseline imbalances, as measured by the Barthel Index (odds ratio [OR], 6.1; 95% confidence interval [CI], 2.5 to 15.1) and by the Glasgow Outcome Scale (OR, 11.6; 95% CI, 4.3 to 30.9). After death was discounted, serious medical complications were associated with severe disability at 3 months as determined by the Glasgow Outcome Scale (OR, 4.4; 95% CI, 1.3 to 14.8). CONCLUSIONS: Medical complications that follow ischemic stroke not only influence mortality but may influence functional outcome.

Calcium/calmodulin-dependent protein kinase II activity in focal ischemia with reperfusion in rats.

BACKGROUND AND PURPOSE: Evidence linking changes in calcium/calmodulin-dependent protein kinase II activity with ischemic cell death has been reported in animal models of global ischemia. The purpose of this study was to delineate the course of these changes after focal ischemia and to clarify the relation of changes in activity of calcium/calmodulin-dependent protein kinase II to the process of ischemic cell death. METHODS: Change in calcium/calmodulin-dependent protein kinase II activity was evaluated in a rat model of focal ischemia after 5 minutes, 30 minutes, and 1 hour of tandem middle cerebral artery and common carotid artery occlusion both with and without reperfusion. RESULTS: Calcium/calmodulin-dependent protein kinase II activity was significantly decreased after all three durations of ischemia followed by immediate decapitation compared with sham-operated animals, in both ischemic core and border-zone regions (P < .05 for all groups). Depression of activity occurred in a regionally graded fashion, with the most severe decrease in infarct core and progressively smaller decreases in samples moving out from the center, corresponding to the severity of histological injury later detected in infarct core and border-zone regions. There were only minor differences between the three durations of ischemia in the degree of enzyme depression noted in the more peripheral regions, indicating that the initial decrease in calcium/calmodulin-dependent protein kinase II activity is an early, sensitive marker for an ischemic insult. After reperfusion, the differences between the 5-minute group and longer periods of ischemia widened because of an increase toward baseline in the 5-minute group and a trend toward further decrease in the 30- and 60-minute groups. CONCLUSIONS: The extreme sensitivity of calcium/calmodulin-dependent protein kinase II to focal ischemia and the parallel temporal and regional changes in its activity to those of more delayed cell injury point to a potential role for this enzyme in the process of excitotoxic injury.

Value of single-photon emission-computed tomography in acute stroke therapeutic trials.

BACKGROUND AND PURPOSE: New therapeutic interventions for acute ischemic stroke are aimed at improving cerebral blood flow in the first 3 to 6 hours after symptom onset. Single-photon emission-computed tomography (SPECT) performed in the setting of clinical therapeutic trials may give us a better understanding of the physiological response to new forms of treatment and could impact acute management decisions. METHODS: We prospectively studied 15 patients with hemispheric ischemic stroke with SPECT within 6 hours of symptom onset and again at 24 hours. The ischemic defect was assessed in a semiquantitative manner that used computer-generated regions of interest (SPECT graded scale). This measure was correlated with clinical presentation (National Institutes of Health [NIH] Stroke Scale), initial clinical course (change in NIH Stroke Scale), long-term outcome (Barthel Index at 3 months), and complications of cerebral hemorrhage and edema. RESULTS: The severity of the SPECT graded scale on the admission scan correlated with the severity of neurological deficit (admission NIH Stroke Scale) (P < .05) and was positively associated with poor long-term outcome as measured with the Barthel Index (P < .001) and the complications of cerebral hemorrhage and massive cerebral edema (P < .005). In fact, there was a threshold value for the SPECT graded scale above which all patients suffered poor long-term outcome and the complications of cerebral hemorrhage and edema. CONCLUSIONS: The measurement of an ischemic defect using SPECT is a valid assessment of hemispheric stroke severity in the hyperacute setting and may be useful for selecting or stratifying patients in clinical therapeutic trials.

Neuropsychiatric manifestations of defect in mitochondrial beta oxidation response to riboflavin.

A 29 year old woman is described with severe hyperemesis gravidarum, atypical migraine, numerous admissions to hospital for psychiatric illness, non-epileptic seizures, and valproate-induced coma. Metabolic studies and measurement of [9,10(n)-3H]palmitate oxidation by cultured fibroblasts suggested a multiple acyl-CoA dehydrogenation disorder. Treatment with riboflavin abolished headaches and abnormal behaviour and normalised the plasma free carnitine level. Subtle defects in mitochondrial beta oxidation may be a treatable cause of disordered behaviour in adults.

Primary intracerebral Hodgkin's disease: a case report.

The authors report a case of primary intracerebral Hodgkin's disease in an 84-year-old woman who presented with a solitary intraparenchymal parieto-occipital lesion and absence of extracranial disease. The histologic diagnosis of Hodgkin's disease was further confirmed with positive immunohistochemical staining of Hodgkin's mononuclear cells and Reed-Sternberg cells and electron microscopy. Such an initial presentation of a solitary intracerebral tumor is extremely rare in Hodgkin's disease. This case helps establish primary intracerebral Hodgkin's disease as a true entity.

In vitro assessment of viral antigen content in inactivated aluminum hydroxide adjuvanted vaccines.

Antigen capture enzyme immunoassays (ELISA) were developed to assess the antigenic content of inactivated aluminum hydroxide (AH) adjuvanted porcine parvovirus, pseudorabies, and infectious bovine rhinotracheitis vaccines. Reference preparations of these viruses were constructed as a basis for comparison. Because AH-associated ELISA interference was largely circumvented, the need for isotopic or complex antigen-adjuvant desorption methods was eliminated. A 4-parameter logistic model related optical density to vaccine dilution. High correlation coefficients (r) were routinely achieved with commercial monovalent and polyvalent vaccines, and reference preparations. The procedure quantified antigen in both aqueous and AH-associated phases. The method may be generally applicable as a partial substitute for in vivo vaccine potency testing by allowing in vitro estimation of inactivated viral antigenic content in AH adjuvanted vaccines.

Competitive and blocking enzyme-linked immunoassay for detection of fetal bovine serum antibodies to bovine viral diarrhea virus.

A competitive blocking enzyme-linked immunoassay (CELIA) was developed to detect bovine viral diarrhea virus (BVDV) antibodies in undiluted fetal bovine serum (FBS). The CELIA was based on competition of serum BVDV antibodies with biotin-labelled anti-BVDV immunoglobulins (Ig) for a limited quantity of solid-phase BVDV antigen. Antigen preparation was simple, FBS could be tested undiluted, and detergent-containing washes were unnecessary. A series of dilutions of postnatal bovine BVDV antiserum prepared in FBS and a set of 147 undiluted abbatoir FBS samples were tested by both CELIA and serum neutralization tests (SNT). CELIA results on both sets of specimens correlated positively with SNT titers (r = 0.99 and r = 0.85). Relative to the SNT, CELIA sensitivity was 100%; specificity was 76%. CELIA detected a level of BVDV antibody below the 1:2-titer threshold detectable with the SNT. Advantages, limitations, and theoretical differences between the CELIA and SNT are discussed. A similar comparison of CELIA with non-competitive enzyme-linked immunoassay approaches to BVDV serodiagnosis is made. It is concluded that the CELIA is valuable in selecting only BVDV-seronegative FBS for use in virologic cell culture media.

Tolerance and dependence after chronic administration of clonidine to the rat.

Acute administration of clonidine (10-70 microgram/kg, IP) disrupted operant behavior maintained by a fixed ratio schedule of reinforcement [1]. When chronically administered (100 microgram/kg, IP and 3 microgram/ml in drinking water) tolerance to the behavioral depressant effect developed within a few days and was complete by 14 days. Abrupt termination of drug treatment in tolerant rats resulted in an abstinence reaction which was characterized by suppression of operant performance for as long as one week. These results demonstrated the development of tolerance to and dependence on clonidine in rats. These behavioral observations in rats may be related to rebound hypertension and irritability of patients given this alpha-adrenergic agonist for treatment of hypertension.

Transmissible gastroenteritis of swine. Efficacy assay of an intramammary use vaccine.

TGE seronegative pregnant gilts were vaccinated by intramammary inoculations with a chemically inactivated (betapropiolactone) cell culture virus vaccine and their nursing pigs were exposed to virus at three days of age. The pig morbidity and survival rates were compared with those of pigs nursing gilts exposed orally to virulent TGE virus during late gestation and also with pigs nursing non-vaccinated seronegative sows. The morbidity rates were 100%, 19% and 19%, while the survival rates were 33%, 100% and 17% respectively. The intramammary vaccine used to vaccinate pregnant gilts in this study did not stimulate sufficient antibody response to provide an acceptable level of protection to nursing pigs against experimental challenge with virulent TGE virus. The serum, colostrum and milk TGE neutralizing antibody responses are reported.