Distribution of N- and O-linked oligosaccharides on surface of spermatozoa from normal and infertile subjects

Sperm glycocalyx modifications are very important for gamete recognition and fertilisation in mammals. These processes may be associated with specific changes in the content and distribution of surface carbohydrates. The purpose of this study was to determine the distribution of surface carbohydrates in human spermatozoa from normal and oligospermic subjects. Fifteen ejaculates each from normal fertile and oligospermic individuals were analysed. N-linked and O-linked surface carbohydrates were detected by fluorescence microscopy using fluorescein isothiocynate-conjugated lectins. Triticum vulgaris agglutinin (WGA)-binding sites were found to be decreased on acrosomal domain in spermatozoa from oligospermic individuals, while no changes were observed in the binding sites of Concanavalin ensiformis, Peanut agglutinin and Lens clunaris agglutinin. A reduction in binding sites for soybean agglutinin and Ricinus communis agglutinin was observed on the acrosomal domains in spermatozoa from oligospermic individuals. Changes in sperm glycocalyx observed in this study provide new insights into molecular rearrangement of sperm membrane in infertility.     

Do coronary artery bypass grafts using cephalic veins have a satisfactory patency?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether using the cephalic vein from the arm for coronary artery bypass grafts achieves an adequate patency rate. Only 219 papers were identified on Medline using the reported search and hand-searching of reference lists. Fourteen papers represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. The patency rate seems to be in the order of 50% at around three years for cephalic veins used for coronary bypass grafting, and this was variable. In addition, we identified only 181 cephalic veins used for coronary bypass grafting in the literature from seven papers. In lower extremity bypass procedures over 900 uses of the cephalic vein have been documented but again patency seems to be around 50% at three to five years. Arterialisation of the vein using an arteriovenous fistula, or angioscopy, have both been used as an attempt to improve patency. In addition, a large proportion of the reported cephalic veins for coronary grafting were used for sequential bypass grafting which may have affected patency rates. Thus, in summary, the patency of the cephalic vein used for coronary artery bypass grafting is around 50% at three years.     

The role of the amino acid residue at alpha1:189 in the binding of neuromuscular blocking agents to mouse and human muscle nicotinic acetylcholine receptors

BACKGROUND AND PURPOSE: Nicotinic acetylcholine receptors (AChRs) are valuable therapeutic targets. To exploit them fully requires rapid assays for the evaluation of potentially therapeutic ligands and improved understanding of the interaction of such ligands with their receptor binding sites. EXPERIMENTAL APPROACH: A variety of neuromuscular blocking agents (NMBAs) were tested for their ability to inhibit the binding of [(125)I]alpha-bungarotoxin to TE671 cells expressing human muscle AChRs. Association and dissociation rate constants for vecuronium inhibition of functional agonist responses were then estimated by electrophysiological studies on mouse muscle AChRs expressed in Xenopus oocytes containing either wild type or mutant alpha1 subunits. KEY RESULTS: The TE671 inhibition binding assay allowed for the rapid detection of competitive nicotinic AChR ligands and the relative IC(50) results obtained for NMBAs agreed well with clinical data. Electrophysiological studies revealed that acetylcholine EC(50) values of muscle AChRs were not substantially altered by non-conservative mutagenesis of phenylalanine at alpha1:189 and proline at alpha1:194 to serine. However the alpha1:Phe189Ser mutation did result in a 3-4 fold increase in the rate of dissociation of vecuronium from mouse muscle AChRs. CONCLUSIONS AND IMPLICATIONS: The TE671 binding assay is a useful tool for the evaluation of potential therapeutic agents. The alpha1:Phe189Ser substitution, but not alpha1:Pro194Ser, significantly increases the rate of dissociation of vecuronium from mouse muscle AChRs. In contrast, these non-conservative mutations had little effect on EC(50) values. This suggests that the AChR agonist binding site has a robust functional architecture, possibly as a result of evolutionary 'reinforcement'.     

Development of an in vitro model to study clot lysis activity of thrombolytic drugs

Background

Thrombolytic drugs are widely used for the management of cerebral venous sinus thrombosis patients. Several in vitro models have been developed to study clot lytic activity of thrombolytic drugs, but all of these have certain limitations. There is need of an appropriate model to check the clot lytic efficacy of thrombolytic drugs. In the present study, an attempt has been made to design and develop a new model system to study clot lysis in a simplified and easy way using a thrombolytic drug, streptokinase.

Methods

Whole blood from healthy individuals (n = 20) was allowed to form clots in a pre-weighed sterile microcentrifuge tubes; serum was removed and clot was weighed. After lysis by streptokinase fluid was removed and remnants of clot were again weighed along with the tube. Percentage of Clot lysis was calculated on the basis of the weight difference of microcentrifuge tubes obtained before and after clot lysis.

Results

There was a significant percentage of clot lysis observed when streptokinase was used. On the other hand with water (negative control), minimal (2.5%) clot lysis was observed. There was a significant difference between clot lysis done by streptokinase and water.

Conclusion

Our study could be a rapid and effective methodology to study clot-lytic effect of newly developed drugs as well as known drugs.

     

Correlation between Abetax-40-, Abetax-42-, and Abetax-43-containing amyloid plaques and cognitive decline.

CONTEXT: Accumulation of senile plaques containing amyloid beta (Abeta)-protein is a pathologic hallmark of Alzheimer disease. Amyloid beta-peptide is heterogeneous, with carboxyterminal variants ending at residues Val40 (Abetax-40), Ala42 (Abetax-42), or Thr43 (Abetax-43). The relative importance of each of these variants in dementia or cognitive decline remains unclear. OBJECTIVE: To study whether Abeta deposition correlates with dementia and occurs at the earliest signs of cognitive decline. DESIGN, SETTING, AND PATIENTS: Postmortem cross-sectional study comparing the deposition of Abeta variants in the prefrontal cortex of 79 nursing home residents having no, questionable, mild, moderate, or severe dementia. MAIN OUTCOME MEASURES: Levels of staining of Abeta-peptides ending at amino acid 40, 42, or 43 in the frontal cortex, as a function of Clinical Dementia Rating score. RESULTS: There were significant deposits of all 3 Abeta species that strongly correlated with cognitive decline. Furthermore, deposition of Abetax-42 and Abetax-43 occurred very early in the disease process before there could be a diagnosis of Alzheimer disease. Levels of deposited Abetax-43 appeared surprisingly high given the low amounts synthesized. CONCLUSIONS: These data indicate that Abetax-42 and Abetax-43 are important species associated with early disease progression and suggest that the physiochemical properties of the Abeta species may be a major determinant in amyloid deposition. The results support an important role for Abeta in mediating initial pathogenic events in Alzheimer disease dementia and reinforce that treatment strategies targeting the formation, accumulation, or cytotoxic effects of Abeta should be pursued.     

Bitter sweet tympani

During cholesteatoma surgery, the chorda tympani nerve must often be divided. We present an interesting case of a patient whose severe dysgeusia due to cholesteatoma resolved following section of the chorda tympani nerve.     

Atherosclerotic risk factors in adolescents

Methods We studied 200 school going children age ranging 12–18 yr with regard to their nutritional intake, family history, anthropometric measurements, blood pressure and lipid profile. Results It was observered that adolescents received less energy from carbohydrates and more from fats in comparison to the recommended standard. Sodium intake was found to be very high whereas fibre intake was low. The prevalence of hypertension was 1.5% and hypercholesterolemia 50%. The high prevalence of hypercholesterolemia was related mainly to dietary habits of these children. Thus our study shows that for the prevention of adult atherosclerotic cardiovascular disease in Indian population measures are urgently needed towards behavioral and life style modification including change in dietary habits.     

Apolipoprotein E-η4 allele and familial risk in Alzheimer's disease

Recent studies have found an association between presence of apolipoprotein E (APOE) η4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the η4 allele with the relatives of AD probands not carrying η4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying η4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age ≥ 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the η4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the η4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without η4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with η4 (3.1-fold increase) was found compared to relatives of probands without η4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-η4 allele relative to controls suggests that familial factors in addition to APOE-η4 are risk factors for AD. Differential censorship from increased mortality of heart diseases may have prevented a higher incidence of PPD among the relatives of probands with η4. © 1996 Wiley-Liss, Inc.