Effect of Sar1-Ileu8-angiotensin on renal prostaglandin E2 biosynthesis and excretion

To test the hypothesis that renal prostaglandin (PG) biosynthesis is regulated by angiotensin (AII), rabbits were given prolonged treatment with the AII analogue, Sar1-Ileu8AII (200 micrograms/kg/4 hr, subcutaneously), for 2 days during a low, normal, and high sodium intake. Sodium restriction augmented plasma renin activity (PRA), which was associated with a rise in basal renal PGE2 synthesis and urinary excretion, whereas sodium supplementation attenuated PRA with a decrease in renal PGE2 synthesis and urinary excretion. Sar1-Ileu8AII administration, with either a low, normal, or high salt intake, suppressed PRA. Sar1-Ileu8AII injection with a low sodium intake also suppressed renal PGE2 synthesis and excretion that was associated with a fall in blood pressure, suggesting an antagonistic action of this agent on vascular beds and renal PGE2 synthesis. On the other hand, with a high sodium intake Sar1-Ileu8-AII increased renal PGE2 synthesis and excretion as well as blood pressure, revealing an agonistic action of this compound under these conditions. The results suggest that exogenous AII analogue may act as an antagonist or agonist depending on sodium intake and endogenous AII levels, renal PGE2 synthesis is dependent on AII levels, either endogenously produced or exogenously administered (as an AII agonist), and the action of AII analogue on vascular beds and renal PGE2 synthesis does not appear to parallel its action on renin-AII feedback regulation at the juxtaglomerular cell especially under conditions of high sodium intake.     

Case study: survey of patient satisfaction with prosthesis quality and design among below-knee prosthetic leg socket users

The aim of this case study was to explore patient satisfaction with the quality of prosthetic leg sockets intended for persons with lower limb amputations. A qualitative study based on in-depth interviews, preceded by a questionnaire session, was carried out with patients from the Rehabilitation Center and Hospital in Malaysia. Twelve out-patient and in-patient amputees with lower limb amputations, specifically below-knee amputations, were chosen randomly. The analysis of patients’ narratives aimed to identify the functional and esthetic characteristics of currently used prosthetic leg sockets and any problems related to them. The obtained results indicated that out of the 12 participants, 41.7% and 25% were satisfied and somewhat satisfied with their current prosthetic sockets. Durability and comfort were rated by the participants as the most important characteristics of prosthetic sockets, with 83.3%. As regards the esthetic appearance of the socket, 66.7% of the respondents considered that the most important feature was the material from which the socket was fabricated. Thus, we conclude that current satisfaction levels with the quality of prosthetic sockets among amputees in Malaysia are suitable, prosthesis being preferred by many amputees. The results can be used to direct future research on cosmesis and functionality of prosthetic socket design.

• Implications for Rehabilitation

• Case study will help participants to get cost effective prosthetic leg socket.

• Develop prosthetic leg socket comfortable as comparative to existing one.

• Help Malaysian government to make policy to develop local prosthetic leg socket at affordable price.

     

Kinetics and molecular docking of dihydroxanthyletin-type coumarins from <Emphasis Type="Italic">Angelica decursiva</Emphasis> that inhibit cholinesterase and BACE1

In the present study, we investigated the anti-Alzheimer’s disease (AD) potential of six dihydroxanthyletin-type coumarins, 4′-hydroxy Pd–C-III (1), decursidin (2), Pd–C-I (3), 4′-methoxy Pd–C-I (4), Pd–C-II (5), and Pd–C-III (6) from Angelica decursiva by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Coumarins 1–6 exhibited dose-dependent inhibition of AChE, BChE, and BACE1. IC₅₀ values were 1.0–4.01 µM for AChE, 5.78–13.91 µM for BChE, and 1.99–17.34 µM for BACE1. Kinetic studies revealed that 1 was noncompetitive inhibitor for AChE, while 2–6 were mixed-type inhibitors of AChE. Compounds 1, 5 and 6 had mixed-type inhibitory effects against BChE; 2 was a competitive inhibitor; and 3 and 4 were noncompetitive inhibitors. Against BACE1, compounds 1, 2, 3, 5 showed mixed-type inhibition and 4, 6 were noncompetitive inhibitors. Molecular docking simulation of the compounds demonstrated negative-binding energies indicating high proximity to the active site and tight binding to the enzyme. These data suggested that the compounds inhibited AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for AD treatment.     

Treatment of pterygium with conjunctival limbal autograft and mitomycin C--a comparative study

A total of 60 eyes with primary progressive pterygium were selected. They were randomly divided into two groups ie, group A and group B each consisting of 30 eyes. Group A patients were treated with pteryglum excision with ipsilateral conjunctival-limbal autografting. Group B patients were treated with pterygium excision followed by mitomycin C 0.02% for two minutes. Both groups were followed up for one year postoperatively to document recurrence rates and postoperative complications. In group A recurrence rate was 3.0% with minimal ocular complication after one year follow-up. But in group B recurrence rate was high as 10.0% and ocular complications were significant after the same period of postoperative follow-up. Both conjunctival-limbal autograft and intra-operative mitomycin use are effective method of surgical treatment of pterygium but considering the rate of recurrence and other postoperative ocular morbidity conjunctival-limbal autografting seems to be the best method of pterygium treatment.     

ACTH producing pulmonary carcinoid and pituitary macroadenoma: a fortuitous association?

We report a case of a 45 year-old man who presented initially with a non-functioning pituitary macroadenoma. A routine chest radiography done preoperatively revealed a right lung nodule which was confirmed by computed tomography (CT) of the thorax. Transfrontal hypophysectomy was performed while a conservative approach was taken for the lung nodule. Four years later, he presented acutely with adrenocorticotrophic hormone (ACTH) dependent Cushing's syndrome which resolved following a right lobectomy. Histological examination revealed an atypical carcinoid. To our knowledge, this is the first reported case of an ectopic ACTH secreting pulmonary carcinoid found in association with a non-functioning pituitary macroadenoma.     

Waterborne Phenanthrene Modulates Immune,Biochemical, and Antioxidant Parameters in the Bloods of Juvenile Olive Flounder

Objective

The current study aimed to evaluate potential effect of waterborne phenanthrene (Phe) on immune, biochemical, and antioxidant parameters in the blood of juvenile olive flounder (Paralichthys olivaceus).

Methods

Juvenile olive flounder were exposed to different concentrations (control, 0.1, 0.5, and 1.0 μg L^-1) of Phe for 14 days and bloods were sampled at day 7 and 14. Hematological (alternative complement activity, ACH50; lysozyme; total immunoglobulin, Ig; cortisol; Hemoglobin, Hb; red blood cell, RBC; white blood cell, WBC), biochemical (glucose; albumin; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline aminotransferase, ALP), lipid peroxidation marker malondialdehyde (MDA), and antioxidant (glutathione, GSH; catalase, CAT; superoxide dismutase, SOD) parameters were evaluated in the blood samples.

Results

ACH50, lysozyme, Ig, and WBC values were significantly decreased by 1.0 μg L^-1 of Phe at day 14, while cortisol level was significantly increased by 0.5 and 1 μg L^-1 of Phe at day 14. Total protein concentration was significantly decreased in the 1.0 μg L^-1 Phe-exposed blood sample at day 7 and 14. Values for ALT, AST, and ALP were significantly increased in response to 0.5 and 1.0 μg L^-1 of Phe at day 14. There was no significant change in Hb, RBC, albumin, and glucose upon Phe. MDA content was significantly increased by 1.0 μg L^-1 of Phe at day 14. GSH content was significantly elevated upon 1.0 μg L^-1 of Phe at day 7, while the content was significantly depleted at day 14. The enzymatic activities of CAT and SOD were significantly increased by 0.5 and 1.0 μg L^-1 of Phe at day 14.

Conclusion

The results indicate significant modulatory effects of waterborne Phe on immune, biochemical, and antioxidant parameters in the economically important fish. The modulations can be used as potential biomarkers in Phe-contaminated aquatic environment.

     

Hereditary Tyrosinemia and the Heme Biosynthetic Pathway. PROFOUND INHIBITION OF δ-AMINOLEVULINIC ACID DEHYDRATASE ACTIVITY BY SUCCINYLACETONE

Succinylacetone (4,6-dioxoheptanoic acid) is an abnormal metabolite produced in patients with hereditary tyrosinemia as a consequence of an inherited deficiency of fumarylacetoacetate hydrolase. It is known that patients with this hereditary disease excrete excessive amounts of δ-aminolevulinic acid (ALA) in urine and that certain patients have an accompanying clinical syndrome resembling that of acute intermittent porphyria (AIP). In order to elucidate the relation of succinylacetone to the heme biosynthetic pathway, we have examined the effects of this metabolite on the cellular heme content of cultured avian hepatocytes and on the activity of purified ALA dehydratase from normal human erythrocytes and from mouse and bovine liver. Our data indicate that succinylacetone is an extremely potent competitive inhibitor of ALA dehydratase in human as well as in animal tissues. By using purified preparations of the enzyme from human erythrocytes and mouse and bovine liver, an inhibitor constant ranging from 2 × 10^-7 M to 3 × 10^-7 M was obtained. In cultured hepatocytes, succinylacetone also inhibited ALA dehydratase activity, decreased the cellular content of heme and cytochrome P-450, and greatly potentiated the induction response of ALA synthase to drugs such as phenobarbital, chemicals such as allylisopropylacetamide and 3,5-dicarbethoxy-1,4-dihydrocollidine, and natural steroids such as etiocholanolone. Four patients with hereditary tyrosinemia have been studied and all were found to have greatly depressed levels of erythrocyte ALA dehydratase activity and elevated concentrations of this inhibitor in urine. These findings indicate that tyrosinemia is a disorder of special pharmacogenetic interest because succinylacetone, an abnormal product of the tyrosine metabolic pathway, resulting from the primary gene defect of the disease, profoundly inhibits heme biosynthesis in normal cells through a blockade at the ALA dehydratase level, leading to clinical and metabolic consequences that mimic another genetic disease, AIP.