Characterization of prostaglandin production in tissue culture of rat renal medullary cells

The purpose of our studies was to examine the role of the nervous system in arrhythmias produced by digitalis overdose and coronary artery occlusion in the cat. This was done by observing the effect of these arrhythmogenic procedures on cardiac efferent neural activity and then determining whether any observed alteration in neural activity contributed to the cardiac rhythm disturbances evoked by digitalis and coronary artery occlusion. Our data indicate that both procedures used to evoke arrhythmias activate each division of the autonomic nervous system. Activation of the sympathetic nervous system resulted in a deleterious effect on cardiac rhythm whereas activation of the parasympathetic nervous system, in general, resulted in a beneficial effect on cardiac rhythm. With coronary occlusion, the role exerted by the nervous system depended on the anatomic location of the involved myocardium. Studies directed at elucidating the mechanisms whereby the nervous system caused cardiac rhythm disturbances indicated that there may be an important difference between the antiarrhythmic efficacy of beta-adrenergic blockade and bilateral stellate ganglionectomy. The latter procedure proved to be a more effective way of removing deleterious sympathetic neural effects on the heart. In conclusion, our findings suggest that the development of new drugs for treating arrhythmias resulting from digitalis and coronary occlusion should be aimed at finding drugs that act to either depress central sympathetic outflow or enhance parasympathetic effects on the ventricle.     

Methamphetamine impairs sexual motivation but not sexual performance in male Japanese quail.

The present study investigated the effects of chronic pre-exposure to methamphetamine on sexual motivation and performance in male Japanese quail. Quail were pre-exposed to methamphetamine (1.0 or 3.0 mg/kg ip) or saline (ip) once daily for 10 days and locomotor activity was measured. After a 10 day washout period, sexual motivation was measured in a straight-arm runway with visual access to a female at one end. Three to 5 hr after sexual motivation tests, males were allowed to copulate with a receptive female quail and copulatory behavior was assessed. Tests were conducted once per day for 10 days. Results showed that males pre-exposed to methamphetamine had decreased locomotor activity compared to saline controls. Males pre-exposed to METH later ran slower toward a female in the runway and spent less time near her. In contrast, methamphetamine pre-exposed males showed similar copulatory behavior as saline pre-exposed males. The findings suggest that chronic pre-exposure to methamphetamine may impair sexual motivation but not sexual performance. The findings are discussed from a comparative perspective and with regard to their clinical relevance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DNA vaccination against Theiler''s murine encephalomyelitis virus leads to alterations in demyelinating disease

Using glycerinated spasmoneme of giant Zoothamnium sp., the physical properties of spasmoneme before and after Ca2+-induced contraction (pCa 4.5) were investigated. The volume change of spasmoneme contraction was measured under zero tension. The length and diameter decreased by about 50% of their initial value as a result of contraction, which means that contraction is nearly isotropic. Thus the volume of spasmoneme decreased drastically by 86% of its original value. The swollen ratio of extended and contracted spasmoneme were 0.07 and 0.37, respectively. Tension-extension relationships of extended and contracted spasmonemes were measured. By applying the theory of rubber elasticity, the number of segments of a chain in originally extended spasmoneme was only 3.3, i.e., the chain was almost a straight one. On the other hand, the number of segments of a chain in contracted spasmoneme was more than 100, i.e., the chain was essentially a random one. Furthermore, the total number of chains in single spasmoneme was the same in extended and contracted spasmoneme. This means that the interchain cross-links of chains were not influenced by addition or removal of Ca2+. Moreover, the molecular weight of a chain is estimated to be at most about 50 kd. By considering all these results, it is concluded that the contractile mechanism of spasmoneme originates in the intramolecular folding and unfolding induced by Ca2+ binding and detaching.     

Outcome of long-term enteral feeding

In the past two decades, many technical advances have made tube enteral feeding much more comfortable and acceptable to patients and their families. This has greatly expanded the use of this therapy, both in clinical conditions where it was traditionally prescribed and in many other diagnoses. This expanded use raises important questions about how much enteral nutrition is being used, the medical outcome in different clinical conditions, and the quality of life experienced by long-term therapy users. This article addresses these outcome issues for patients in the nonhospital setting.     

Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues

The stereoelectronic requirements for interaction of the southern aliphatic hydroxyl of cannabimimetic pharmacophores with the CB1 and CB2 receptors are explored. The stereoselective syntheses of three series of classical/nonclassical hybrid cannabinoids are described. These compounds were designed to investigate the importance of the southern aliphatic hydroxyl (SAH) pharmacophore for cannabimimetic activity. Variation in the chain length of the SAH moiety in these 6beta-(hydroxyalkyl)dihydrobenzopyran analogues, from 6beta-hydroxymethyl to 6beta-(omega-hydroxyethyl) and 6beta-(omega-hydroxypropyl), and the effects of replacing the hydroxyl functionality by hydride and iodide are reported. Our results indicate that the SAH pharmacophore has less pronounced effects than the C-3 aliphatic chain on cannabinoid activity. Furthermore, it appears that this southern molecular component is capable of interacting with two different subsites on the receptor and that the nature of this interaction is determined by the terminal substituent on the C-6beta alkyl group. One of the subsites can accommodate the relatively polar SAH pharmacophore, while the second subsite interacts with more hydrophobic C-6beta substituents and can accommodate large spherical pharmacophores separated by three methylene carbons from the tricyclic cannabinoid template.     

Diabetic ketoacidosis and rhabdomyolysis following excessive intake of a weight reducing diet

We describe two unusual cases in sheep of subclinical mastitis caused by Streptococcus parasanguinis. This bacterium has been associated with the development of experimental endocarditis; its presence at relatively high concentrations in apparently healthy sheep milk may pose a health risk in persons with predisposing heart lesions.     

A preventive registry for hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic disorder characterized by a strong family history of colorectal and extracolonic cancers, usually at a young age. This article presents a new provincial service for families with HNPCC. The Steve Atanas Stavro Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital is accruing patients that meet a set of criteria establishing a putative diagnosis of HNPCC. The objectives of the Registry are to develop and assess patient pedigrees, to coordinate screening procedures for at-risk persons, to maintain a prospective database of patient information, to provide education and support for families and to contribute to research. To date, surgeons and patients are the most common referral sources, while oncologists and geneticists are the least common. The ultimate goal of the HNPCC service is the secondary prevention of cancer and a corresponding decrease in mortality for HNPCC family members.     

Coronal and sagittal clefts in skeletal dysplasias

Objective. To assess the role of coronal and sagittal vertebral clefts in diagnosing skeletal dysplasias. Material and Methods. A search in the database at the International Skeletal Dysplasia Registry revealed 40 different diagnoses in which coronal or sagittal clefts were present, the major groups being: atelosteogenesis, chondrodysplasia punctata, dyssegmental dysplasia, Kniest dysplasia and short rib polydactyly syndrome. We reviewed all firm cases with both AP and lateral films of the spine in these major groups (n = 143), with patients' ages ranging from 20 weeks of gestation up to 26 years of age. Results. Ninety-four percent of all clefts were found in children less than 1 year of age, mainly located in the thoracolumbar region. Fifty-six percent of the clefts were observed in boys. Coronal clefts were more common than sagittal clefts. Clefts were most frequently observed in atelosteogenesis (88%), followed by chondrodysplasia punctata (79%), dyssegmental dysplasia (73%), Kniest dysplasia (63%) and short rib polydactyly syndrome (53%). Conclusion. Vertebral clefts are of major diagnostic value in the groups mentioned above, especially before 1 year of age. The search did not come up with new entities in which vertebral clefts are of major diagnostic value.     

Time-resolved FTIR studies of the GTPase reaction of H-ras p21 reveal a key role for the beta-phosphate

FTIR difference spectroscopy has been established as a new tool to study the GTPase reaction of H-ras p21 (Ras) in a time-resolved mode at atomic resolution without crystallization. The phosphate vibrations were analyzed using site specifically 18O-labeled caged GTP isotopomers. One nonbridging oxygen per nucleotide was replaced for an 18O isotope in the alpha-, beta-, or gamma-position of the phosphate chain. In photolysis experiments with free caged GTP, strong vibrational coupling was observed among all phosphate groups. The investigation of Ras*caged GTP photolysis and the subsequent hydrolysis reaction of Ras*GTP showed that the phosphate vibrations are largely decoupled by interaction with the protein in contrast to free GTP. The characteristic isotope shifts allow band assignments to isolated alpha-, beta-, and gamma-phosphate vibrations of caged GTP, GTP, and the liberated inorganic phosphate. The unusually low frequency of the beta (PO2-) vibration of Ras-bound GTP, as compared to free GTP, indicates a large decrease in the P-O bond order. The bond order decrease reveals that the oxygen atoms of the beta (PO2-) group interact much more strongly with the protein environment than the gamma-oxygen atoms. Thereby, electrons are withdrawn from the beta-phosphorus, and thus also from the beta/gamma-bridging oxygen. This leads to partial bond breakage or at least weakening of the bond between the beta/gamma-bridging oxygen and the gamma-phosphorus atom as a putative early step of the GTP hydrolysis. Based on these results, we propose a key role of the beta-phosphate for GTP hydrolysis. The assignments of phosphate bands provide a crucial marker for further time-resolved FTIR studies of the GTPase reaction of Ras.