Synthesis of 3-Amino-2-(3-indolyl)propanol and Propanoate Derivatives and Preliminary Cardiovascular Evaluation in Rats

A series of tryptamine analogues has been prepared and tested for their 5-HT₁ receptor agonist properties. The incorporation of an alkoxy group at the C-5 position of the indole nucleus resulted in a short-lived and dose-dependent immediate antihypertensive and bradycardic response in anaesthetized spontaneously hypertensive rats (SHR). In addition, a carbomethoxy function at the β-position of the side-chain of the tryptamines significantly increased the mean resting arterial blood pressure (MAP) in pithed rats and also produced contraction of the canine basilar artery in a dose-dependent fashion. Structure-activity relationships (SAR) suggest that the 5-alkoxy group is an important pharmacophore in the production of the antihypertensive effect and that the introduction of a hydroxymethylene group on the side-chain, instead of the carbomethoxy group, changed the receptor affinity profile.     

Removal of Infected Dual Chambered Transvenous Pacemaker and Implantation of a New Epicardial Dual Chambered Device with Cardiopulmonary Bypass: Experience with Seven Cases

ABAD, C., et.al .: Removal of Infected Dual Chambered Transvenous Pacemaker and Implantation of a New Epicardial Dual Chambered Device with Cardiopulmonary Bypass: Experience with Seven Cases . Seven patients with infected transvenous dual chambered pacemakers have undergone removal of the device using cardiopulmonary bypass. There were four women and three men with a mean age of 58 years. Six patients had localized infection in the generator pocket (mean of 4.6 previous unsuccessful operations for surgical sterilization). Four infections were due to Staphylococcus epidermidis, two to Staphylococcus aureus, and one patient presented septicemia caused by Staphylococcus epidermidis and Pseudomonas aeruginosa. The atrial and ventricular transvenous electrodes were removed under direct vision using cardiopulmonary bypass. A new dual chambered epicardial pacemaker was implanted. The procedure was well-tolerated, and all patients are infection free with working pacemakers after a mean follow-up of 25.4 months.     

Calcitriol administration in end-stage renal disease: intravenous or oral?

1,25-Dihydroxyvitamin D deficiency plays an important role in the pathogenesis of secondary hyperparathyroidism, and adequate replacement of this hormone is considered essential to normalize parathyroid gland function and restore bone homeostasis in patients with advanced renal failure. Although initial uncontrolled clinical trials suggested the superiority of intravenous calcitriol treatment, more recent controlled investigations show that different routes (oral versus intravenous), frequency (daily versus intermittent), and dosing (physiological versus pharmacological) of calcitriol administration are clinically equivalent. Overall, the response to calcitriol treatment depends more on the severity of secondary hyperparathyroidism and the presence of confounding variables, such as hyperphosphatemia and acquired abnormalities of parathyroid cell function, than the method of calcitriol administration.     

Hypoglycaemic activity of commelina africana and ageratum conyzoides in relation to their mineral composition

Background

Many plants with antidiabetic properties probably act in part through their content of fibre, vitamins, bioactive or mineral content

Objectives

This study investigated the mineral, proximate, phytochemical compositions and hypoglycaemic effect of Commelina africana and Ageratum conyzoides extracts in diabetic rats, and the likely relationship between this property and the mineral, proximate and phytochemical compositions of the plants.

Methods

The plants were subjected to mineral, proximate composition and phytochemical analysis. Attempt was made to see (if any) the relationship between the hypoglycaemic effect and the mineral, proximate compositions and phytochemistry of the plants. Alloxan-induced diabetic animals were administered 500mg/kg body weight aqueous extracts of the plants and glibenclamide as the reference hypoglycaemic agent.

Results

Aqueous extract of Ageratum conyzoides reduced fasting blood glucose of experimental animals by 39.1% while Commelina africana reduced the same by 78.0%. Alkaloids, cardenolides, saponins, and tannins were detected in both plants. Anthraquinones was absent in C. africana but a trace of it was detected in A. conyzoides. The hypoglycaemic effect of Commelina africana was comparable with the reference hypoglycaemic agent. Ageratum conyzoides showed comparably weaker hypoglycaemic effect than exhibited by reference hypoglycaemic agent. Comparatively, Commelina africana had higher mineral concentrations (except Na) than Ageratum conyzoides.

Conclusions

Plants'' extracts minerals (magnesium, potassium and iron) and bioactive components (alkaloids and cardenolides) seemingly enhanced their hypoglycaemic effect. Furthermore, these minerals, alkaloids and cardenolides could be helpful in ameliorating complications of diabetes like hypertension and cardiovascular disease.     

Contribution of SNRNP200 sequence variations to retinitis pigmentosa

Purpose

Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients.

Methods

Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12–16, 22–32, and 38–45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses.

Results

Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study.

Conclusions

Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP.     

Sickle reticulocytes adhere to VCAM-1

Adherence of sickle (SS) erythrocytes to endothelial cells represents interactions between red blood cell (RBC) and endothelial cell surface molecules. To enhance our understanding of the ligands involved, we transfected COS cells with the cDNAs of two endothelial cell adhesion molecules, VCAM-1 and E-selectin, and measured the binding of normal and sickle RBCs after static incubation. The percentage of COS cells with rosettes (five or more adherent RBCs) was determined. Normal RBCs did not adhere to VCAM-1-transfected COS cells. Unfractionated SS RBCs formed rosettes on the VCAM-1-transfected COS cells (mean +/- SD, 5.85% +/- 4.98%). Low-density SS RBCs were more adherent than high-density SS RBCs (P < .005). The adherent SS RBCs were a young reticulocyte population, staining positively for transferrin receptor. Another measure of reticulocyte age, RNA content, also correlated with adherence. SS RBC binding was specific--inhibitable by antibodies to either VCAM-1 or the alpha 4 integrin chain of VLA-4. In contrast, there was no significant adherence of normal or SS RBCs to E-selectin- transfected COS cells. These results suggest that young reticulocytes bind to endothelial cell VCAM-1 via VLA-4 integrin.