Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.     

Glucosamine-induced insulin resistance in 3T3-L1 adipocytes is caused by depletion of intracellular ATP

Glucosamine, which enters the hexosamine pathway downstream of the rate-limiting step, has been routinely used to mimic the insulin resistance caused by high glucose and insulin. We investigated the effect of glucosamine on insulin-stimulated glucose transport in 3T3-L1 adipocytes. The Delta-insulin (insulin-stimulated minus basal) value for 2-deoxyglucose uptake was dramatically inhibited with increasing concentrations of glucosamine with an ED50 of 1.95 mM. Subcellular fractionation experiments demonstrated that reduction in insulin-stimulated 2-deoxyglucose uptake by glucosamine was due to an inhibition of translocation of both Glut 1 and Glut 4 from the low density microsomes (LDM) to the plasma membrane. Analysis of the insulin signaling cascade revealed that glucosamine impaired insulin receptor autophosphorylation, insulin receptor substrate (IRS-1) phosphorylation, IRS-1-associated PI 3-kinase activity in the LDM, and AKT-1 activation by insulin. Measurement of intracellular ATP demonstrated that the effects of glucosamine were highly correlated with its ability to reduce ATP levels. Reduction of intracellular ATP using azide inhibited Glut 1 and Glut 4 translocation from the LDM to the plasma membrane, insulin receptor autophosphorylation, and IRS-1 tyrosine phosphorylation. Additionally, both the reduction in intracellular ATP and the effects on insulin action caused by glucosamine could be prevented by the addition of inosine, which served as an alternative energy source in the medium. We conclude that direct administration of glucosamine can rapidly lower cellular ATP levels and affect insulin action in fat cells by mechanisms independent of increased intracellular UDP-N-acetylhexosamines and that increased metabolism of glucose via the hexosamine pathway may not represent the mechanism of glucose toxicity in fat cells.     

Infant affect and affect regulation during the still-face paradigm with mothers and fathers: the role of infant characteristics and parental sensitivity

This laboratory study examined mothers' and fathers' sensitivity during face-to-face interactions with their infants as well as infants' affective and regulatory responses during mother-infant versus father-infant still face (SF). The degree to which infant gender and temperament as well as parental sensitivity predicted SF responses was also examined. Participants included 94 healthy, primarily White, middle-class 4-month-olds and their parents. Results indicated that mothers and fathers were equally sensitive toward their infants. Infants' affect and regulatory behaviors were also significantly stable across mother- and father-infant SF situations, although several differences in mean levels of regulation emerged. Finally, the extent to which exogenous and endogenous variables predicted infant SF responses differed as a function of which affect or regulatory variable was being examined and with which parent the infant was experiencing SF.     

Pharmacologic therapy for prostatism

Although the general approach to management of a sufficient degree of benign prostatic hyperplasia in the past was surgical intervention (transurethral resection of the prostate), the current availability of effective pharmacologic therapy has changed the initial management strategy. At present, two types of drugs are available for treatment of prostatism: (1) selective alpha-adrenergic blocking agents (terazosin, doxazosin, and tamsulosin) and (2) an inhibitor of the 5 alpha-reductase enzyme (finasteride). Pharmacologic blockade of the alpha(1)-adrenoceptors is thought to result in relaxation of the smooth muscle in the prostate and bladder neck, which reduces urethral resistance, improves voiding function, and minimizes the symptoms of prostatism. These effects may be noted by the patient within several weeks after initiation of treatment. The mechanism of action of finasteride is a blocking of the conversion of testosterone to dihydrotestosterone and an associated volume shrinkage of the prostate. On the average, a 25% reduction in prostate volume can be achieved, but a period of 12 months or longer of finasteride therapy is needed for maximal shrinkage and maximal decrease in symptoms of prostatism. The expanding population of middle-aged and elderly men with prostatism of moderate severity will undoubtedly prompt the development of additional pharmacologic options for treatment of prostatism and benign prostatic hyperplasia.     

The direct activating effect of a nonapeptide neurohormone (vasotocin) on the thyroid and interrenal glands of sturgeons in in-vitro experiments

An in-vitro effect of nonapeptide neurohormone vasotocin on thyroid and interrenal glands was studied in hybrid of Siberian and Lena sturgeons [correction of salmons] at light microscopy level using morphometric method. At a concentration of 0.1 and 1 nmol/l vasotocin was shown to exert undirectional stimulating effect on the thyroid and interrenal gland functions. In the presence of vasotocin at a concentration of 1 nmol/l in culture media the activity of glands is even more pronounced than under the influence of adenohypophyseal hormones, adrenocorticotropic (8 x 10 ng/ml) and thyrotropic (5 ng/ml).     

Electrodynamic headphones and woofers for application in magnetic resonance imaging scanners

Electrodynamic speakers compatible with (functional) magnetic resonance imaging (MRI) are described. The speakers magnets are removed, their function is replaced by the scanner's magnetic field, resulting in an uncommon but efficient operation. The method can be used with headphones as well as woofers. Functional MRI is not associated with any known biological risks, but as a method for visualization of task-specific activation of brain regions it is undesirably noisy. Thus, it requires both noise protection and efficient sound transmission systems for delivering acoustic stimuli to subjects. Woofers could possibly be used in active noise-control systems. The speakers described in this paper can be used for either task.     

Methotrexate treatment of idiopathic granulomatous hepatitis

OBJECTIVE: To test the efficacy and safety of low-dose oral pulse methotrexate therapy in patients with idiopathic granulomatous hepatitis who had complications of, did not respond to, or refused glucocorticoid therapy. DESIGN: Prospective case study. SETTING: Academic medical center hospital. PATIENTS: Seven patients with biopsy-proven, idiopathic granulomatous hepatitis who could not tolerate or were unresponsive to glucocorticoid therapy. INTERVENTION: Low-dose oral pulse methotrexate, 15 mg/wk. MEASUREMENTS: Temperature, symptoms, dose of concurrent glucocorticoids, biochemical tests of liver function, side effects of methotrexate, and assessment of liver biopsy specimens. RESULTS: All six febrile patients became afebrile within 3 months of starting methotrexate. Fatigue and anorexia improved in all patients. Glucocorticoid therapy was successfully discontinued within 6 months of starting methotrexate in four patients receiving prednisone at entry. Liver biopsy specimens were obtained again after methotrexate therapy and showed absence of granulomas in four of four patients. The minimum effective dose of methotrexate was 0.20 mg/kg body weight per week. No serious adverse effects and no failures to respond to methotrexate therapy were noted in this group of patients. In three patients, methotrexate therapy has been successfully tapered without signs or symptoms of recurrent disease. CONCLUSIONS: Low-dose oral pulse methotrexate was effective in treating patients with granulomatous hepatitis.     

Creutzfeldt-Jakob disease: neurophysiologic visual impairments

OBJECTIVE: The predictive value of electrophysiologic visual testing in Creutzfeldt-Jakob disease (CJD) was investigated, and the retinal pathologic findings in three cases are reported. BACKGROUND: The fatal prognosis of CJD, its transmissibility, and the lack of treatment make early diagnosis essential in averting human-to-human transmission. Electroretinogram and visual evoked potentials have been studied in few cases of CJD. METHODS: A visual electrophysiologic examination was performed in 41 consecutive patients referred with suspected CJD. The disease had been diagnosed in 24 patients (CJD group; 15 were confirmed neuropathologically and 9 by clinicolaboratory methods in accordance with diagnostic criteria). The remaining 17 patients were diagnosed with other neurologic disorders, and served as a control group. RESULTS: Flash electroretinogram revealed a significant decrease in the amplitude of the B1 wave (<60 microV) and the B/A ratio (<2) in the CJD group compared with those in the control group. Flash visual evoked potentials revealed no significant difference in latency, but amplitude was increased (>10 microV) in the CJD group, especially in patients with myoclonus. CONCLUSIONS: The visual electrophysiologic abnormalities provide an interesting noninvasive diagnostic tool in idiopathic CJD. The B1-wave decrease is closely correlated with the outer plexiform layer abnormalities observed on neuropathologic examination.     

Reflections on the Michigan splint and other intraocclusal devices

It seems obvious in retrospect that the treatment of disorders by interocclusal devices followed two paths: stabilization splints and functional orthopedic appliances. The dividing line between them is not always clear. Both have some function related to the position of the mandible. They may not differ significantly in their control of occlusal stability (e.g., telescoping devices anchored to stabilization splints). The stabilization splint, as well as other conservative measures, will play an increasing role in accepted therapy for TMD. The use of anterior repositioning devices for TMD, including MPD syndrome, will decrease. Research may provide answers that allow them to be used more specifically and predictably. Perhaps there will be but little change in their use where there is an association of TMD and Class II malocclusion. There will be an increase in the use of interocclusal devices for the treatment of snoring and obstructive apnea. Some additional directions seem to have emerged in the late 1980s and early 1990s: In the absence of pain and significant debilitation, treatment for TMD, if any, is to be reversible. Prevention or aggravation of TMD should be practiced to the extent possible during dental procedures. One long-term, well-designed, prospective study indicated that the incidence and severity of TMD could be reduced by appropriate occlusal adjustment. There is a small, but nevertheless important minority of patients with TMD who progress to persistent pain and/or dysfunction. Initial management of the vast majority of patents with TMD should be use of noninvasive reversible therapies. Surgery is indicated in only a relatively small percentage of cases of TMD. Research on interocclusal devices should not terminate simply because they are in part dental devices (i.e., biomechanical forms of treatment). The diagnosis and treatment of TMD has been called a dilemma, especially for those patients with chronic pain for whom no treatment has been effective. However, it would be ill-advised to abandon what treatment is already known to be effective by allowing those few but psychosocially important patients with chronic pain to determine what should be done for the vast majority of patients with TMD: reversible forms of treatment, including physiotherapy, pharmacologicals, and the stabilization occlusal bite plane splint.