Potentiation of cholinergic activity with pyridino[1,2-a]imidazo[5,4-b]indole: in vitro studies

1. Effects of a novel imidazoindole derivative on cholinergic function were studied in isolated tissue preparations. 2. The compound demonstrated a dose-dependent (10(-11)-10(-9) potentiation (20-60%) of acetylcholine induced tension in guinea pig ileal tissue. 3. Increases in the size of end-plate potentials and nerve evoked muscle twitches were observed in frog nerve-skeletal muscle preparations. 4. Cholinesterase activity was not inhibited. 5. The results suggest that the compound has actions at the post-synaptic muscarinic receptor complex in smooth muscle and causes pre-synaptic increases in ACh release at the neuromuscular junction.     

Carbon dioxide recruitment threshold as a predictor of successful weaning in chronic obstructive pulmonary disease patients: A pilot study

Abstract Several methods have been used to predict successful weaning and extubation among chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to determine whether carbon dioxide recruitment threshold (PCO₂RT) can be used as adjunct to conventional weaning parameters to predict early weaning and successful extubation. Twelve COPD patients who were ready to be extubated based on conventional weaning parameters were divided into group A ( n = 7) and group B ( n = 5). Group A were those patients with better weaning parameters and hence a higher probability of successful extubation as compared to group B. Carbon dioxide apnoeic threshold (PCO₂AT) was obtained by hyperventilating the patient using an increment of two breaths per min until apnoea occurs. At this point, the PCO₂AT or the PaCO₂ during said apnoeic period was recorded. A dead space of 150 cc is then added to the circuit until the patient starts to breathe as evidenced by the sensitivity trigger indicator. The PCO₂ obtained at this period is termed PCO₂RT. After weaning for 30 min on a T-tube, another arterial blood gas is determined and this is called the PCO₂SB or the CO₂ level after 30 min on spontaneous breathing. If the PCO₂SB-PCO₂RT difference is high with a sensitivity of 85.71% and specificity of 100% vs sensitivity of 57.14% and specificity of 60% using the conventional weaning parameters. Thus an increase in PCO₂SB at 30 min T-tube is indicative of impending respiratory pump failure and that other causes of failure to wean must be investigated.     

Additive effects of CD59 expression in Gal knockout mice in vitro but not in an ex vivo model

Abstract: Transgenic expression of the human complement regulatory molecule CD59 in mice and genetic deletion of the major xenoantigen galactose α 1,3 galactose (Gal KO) each resulted in partial protection of spleen cells from lysis by human serum. These protective effects were additive when the two genetic modifications were combined. However, when the effects of these genetic modifications were examined in an ex vivo model in which mouse hearts were perfused with human plasma, it was Gal KO which was the modification which determined protection. CD59 expression alone was not protective and CD59 expression in combination with Gal knockout did not result in a significant additional increase in protection over and above that provided by Gal knockout alone. The likely explanation for this discrepancy between the in vitro and ex vivo data is that the H2-K^b promoter used to drive CD59 expression results I in substantially less expression on endothelium than on spleen cells.     

Automatic discrimination of myoelectric signals via parallel cascade identification

It has recently been shown that it is possible to discriminate accurately among myoelectric signals underlying different muscle contraction types, specifically elbow flexion and extension and forearm pronation and supination. It was reported that once a number of distinctive features had been extracted from the myoelectric signals, a neural network could be trained to distinguish the contraction types with an impressively high accuracy. In the present paper, we show that a technique known as parallel cascade identification can be used to construct classifiers that can also accurately, differentiate the contraction types. The use of parallel cascades has the benefit of dispensing with the need for feature extraction, so that raw myoelectric signal data can be used directly. In addition, very little data are required to train the parallel cascades to distinguish accurately novel incoming myoelectric signals. Results of using parallel cascades to distinguish foream pronation, supination, and elbow flexion are presented.     

Josephine Goldmark (1877–1950): A Biographic Sketch

Josephine Goldmark was one of those remarkable early-twentieth-century American women who, while seeking independence and fulfillment in their own lives, devoted themselves to humanitarian causes and social reform. She was deeply involved in efforts to improve working conditions for women and children. Her work led her into the arena of nursing, especially public health nursing, where she contributed significantly to the development of the profession.     

Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

Acquired and innate resistance to the haemoflagellate cryptobia salmositica in sockeye salmon (Oncorhynchus nerka)

Juvenile sockeye salmon (Oncorhynchus nerka, Fulton River stock) were protected from otherwise lethal challenges with the haemoflagellate Cryptobia salmositica by acclimation to elevated water temperatures (20 degrees C). Fish treated in this manner displayed increased immunity to C. salmositica and yielded plasma showing enhanced lytic activity against the parasite. The acquired lytic activity was antibody- and complement-mediated. In contrast, a stock of naive O. nerka from Weaver Creek, previously identified as having a high innate resistance to the lethal effects of C. salmositica, also had plasma factors that destroyed the parasite in vitro. This anti-Cryptobia activity also involved complement because 1) it resulted in lysis of the parasite, 2) it was heat-labile (40 degrees C for 20 min), and 3) it was largely removed from the plasma by substances capable of activating (binding) complement by the classical pathway (an antigen:antibody complex of Renibacterium salmoninarum and its specific antibody) and the alternate pathway (Escherichia coli lipopolyssacharide). The complement-mediated lysis associated with innate resistance was apparently the result of activation by the alternate pathway because it occurred in fish lacking antibodies against the parasite. The reaction was unusual in that a long incubation period (about 2 days) was required for maximum lysis of the parasite. At least one component of the innate lytic system depended on disulphide bonds because lytic activity was destroyed by 2-mercaptoethanol.