Aqueous extract of Emblica officinalis was found to be a potent inhibitor of lipid peroxide formation and scavenger of hydroxyl and superoxide radicals in vitro. The amount of the fresh pulp needed to inhibit 50% of lipid peroxidation was 1, 000μg/ml in the Fe2+/ascorbate system and 640μg/ml in the Fe3+/ADP-ascorbate one. The concentration needed for 50% inhibition of superoxide-scavenging activity was 107μg/ml in the method involving photoreduction of riboflavin and 232μg/ml in the xanthine-xanthine oxidase method, and that for hydroxyl radical scavenging (deoxyribose degradation method) was 3, 400μg/ml. An indigenous drug preparation containing Emblica officinalis, used in India as a health tonic, was also found to have a potent antioxidant activity. The antioxidants present in Emblica officinalis were aqueous soluble, but partially extractable with ether, and were heat stable.
When bovine aortic endothelial cells were incubated in Dulbecco's modified Eagle's medium containing 5% fetal bovine serum and 5nmol/ml (in terms of malondialdehyde) of linoleic acid hydroperoxide, release of lactate dehydrogenase (LDH) from the cells into the medium increased over a 2-4h incubation period, reaching a maximum level of about 80% of the total activity of LDH. In the presence of 17β-estradiol (E2) or 2-hydroxyestradiol (2-OHE2), the LDH release was inhibited depending on their concentration. The IC50 values of the inhibition were approximately 5 and 1μM, respectively. The lipid peroxide level in the cultured endothelial cells increased upon incubation with the hydroperoxide, which increase was suppressed markedly by 2-OHE2 and slightly by E2. Lipid peroxidation of low-density lipoprotein was inhibited markedly by 2-OHE2 and slightly by E2.
The effect of pretreatment with Ocimum sanctum, an herbal drug, on HCl-ethanol-induced gastric lesions in rats was investigated with respect to acid/pepsin, lipid peroxidation, antioxidant status, and glycoproteins in the gastric mucosa. The increase in volume and acidity of the gastric juice and the decrease in peptic activity in HCl-ethanol-exposed mucosa were maintained at near normalcy in O. sanctum-pretreated mucosa. The increase in lipid peroxidation, decrease in activity of antioxidants in the ulcerated rats were maintained at normalcy in the pretreated rats. Decrease in protein and glycoprotein of the ulcerated mucosa were found to be maintained to near normal in O. sanctum-treated mucosa. These results suggest that by virtue of its ability to decrease acidity and increase the mucosal defense, the use of O. sanctum as an antiulcerogenic agent is justified.
In order to investigate mucin production in various pathological states, we generated murine monoclonal antibodies (4H6, 2D11) against mucins from bronchio-alveolar lavage fluids (BALE) of hamsters with bronchitis caused by sulfur dioxide exposure. In the immunohistochemical studies, the antibodies recognized the mucins secreted into the tracheal lumen, but not the mucins stored in goblet cells or in submucosal gland mucous cells. ELISA showed that the antibodies react with mucins from hamster intestine and swine stomach, and with BALF of rats, guinea pigs, dogs, and humans. However, the antibodies recognized neither bovine submaxillary gland mucins nor proteoglycans. In conclusion, the ELISA using the monoclonal antibodies is available to quantify airway mucin production.
In different stages of carcinoma of the uterine cervix, the activities of serum 5′-nucleotidase, lactate dehydrogenase (LDH), phosphohexose isomerase (PHI), γ-glutamyl transpeptidase (GGT), transaminases, and phosphatases were studied before and after radiation treatment. Glycolytic enzymes (LDH, PHI) were found to be increased from stage I onwards, whereas GGT, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and acid and alkaline phosphatases increased only in the advanced stages (stages III, IV), when compared with normal values. 5′-Nucleotidase was found to be increased significantly from stage II onwards when compared with the normal. The increased levels of these enzymes were reversed to near normal levels after radiotherapy. The increased levels of serum transaminases, phosphatases, and GGT in the advanced stages of carcinoma of uterine cervix may be explained on the basis of liver involvement and bone metastasis. The degree of increase in the activities of PHI and LDH may reflect the status of the cancer. The activity of 5′-nucleotidase in serum may be used as an additional marker to assess the status of carcinoma of uterine cervix under circumstances when other markers fail to provide clear indications.
Measurement of urinary neopterin, a pteridine derivative, is specially useful for identification of all disease states involving an activated cellular immune system, as is present, for example, during cancer growth and allograft rejections, and in patients infected with intracellular microbes or viruses like human immunodeficiency virus type 1 (HIV-1). The urinary level of total pteridines also has a significant correlation with the incidence of all kinds of cancer. This report presents a direct comparison between the concentrations of neopterin and total pteridines in urine samples from a representative group of normal healthy subjects and cancer patients with acute lymphoblastic leukemia. A close relationship between the excretory levels of both neopterin and total pteridines was observed. The data presented indicate that measurement of neopterin or total pteridines is of equal potential for clinical applications. However, as specific measurement of neopterin by high-performance liquid chromatography or radioimmunoassay techniques being more expensive and time consuming, the rapid measurement of total pteridines should be preferred for routine monitoring of patients under therapy as well as for single-step screening of a population for all disease states associated with an activated cellular immune system.
To compare the efficacy and safety of pravastatin alone and a combination of it and cholestyramine in low doses for the treatment of primary hypercholesterolemia, we conducted a randomized, parallel group study. A total of 30 patients with a mean age of 55 years were enrolled in the study. They were randomized into two groups. One group (n=15) received pravastatin (20mg/day) while the other group (n=15) received pravastatin (10mg/day) plus cholestyramine (8g/day) for 24 weeks. At 12 weeks, results showed that pravastatin alone led to a 21% reduction in total plasma cholesterol and a 24% reduction in low-density lipoprotein (LDL) cholesterol concentrations. There was no significant change in high-density lipoprotein cholesterol and total triglyceride concentrations. In the pravastatin-cholestyramine group, there was similar reduction in total cholesterol concentration (24%). However, the reduction in the LDL cholesterol concentration was higher (32%); and the plasma triglyceride concentration was increased by 13%. No significant side effects occurred in either group during the study period. Similar results were observed at 24 weeks. In conclusion, pravastatin was demonstrated to be an effective, well-tolerated drug for treating hypercholesterolemia. A low dose combination of pravastatin and cholestyramine was significantly more effective than pravastatin alone in higher doses in terms of LDL cholesterol reduction. By use of a lower dose of cholestyramine, the side effects of cholestyramine are much reduced and the patient's compliance is improved.