Role of the water-drinking test in medically treated primary open angle glaucoma patients.

PURPOSE: The water-drinking test (WDT) has recently re-emerged as a possible way to determine the competency of the trabecular meshwork. We performed a prospective interventional study to test the hypothesis that the WDT could be useful in assessing fluctuations in patients undergoing treatment for primary open angle glaucoma (POAG). METHODS: We included 122 patients; 62 on medical treatment for POAG (n=123 eyes) and 60 controls (n=120 eyes). The study group had been on intraocular pressures (IOP) lowering treatment continuously for at least 3months with stable IOP. The WDT was performed during fasting and was considered positive if it fluctuated ≥6mmHg. RESULTS: The patients on medical treatment had a mean age of 50.56±18.45 years vs. 51.35±11.22 for the controls (P=0.34); with 71% being female in the study group and 77% in the control group. In the study group; 52% were on beta blockers (n=64), 27% combination of two or more medications (n=33), 19% prostaglandin analogues (n=24) and 2% alpha agonists (n=2). The WDT was positive in 17.07% (n=21) in the study group and 2.5% (n=3) in the control group (P=0.0001). The mean fluctuation was 7.14±2.15mmHg in the study group and 6.00±0mmHg in the controls (P=0.33). A positive WDT was found in 33.33% (n=11) of those on combination therapy; 12.5% (n=3) prostaglandin analogues and 10.94% (n=7) beta blockers (P=0.03). Combination therapy had the highest positive WDT fluctuation (7.54±2.87) followed by prostaglandin analogues (7.00±1.00) and beta blockers (6.57±0.78) with a P value of 0.44. CONCLUSIONS: The WDT can identify significant fluctuations in eyes with POAG that are medically treated.

The role of prostaglandin and antioxidant availability in recovery from forearm ischemia-reperfusion injury in humans.

BACKGROUND: Endothelial dysfunction, manifesting as attenuated flow-mediated dilation (FMD), is clinically important. Antioxidants may prevent this dysfunction; however, the acute effects of oral administration in humans are unknown. Low flow-mediated constriction (L-FMC), a further parameter of endothelial health, is largely unstudied and the mechanisms for this response unclear. METHODS: Twelve healthy participants (five women and seven men) completed three test conditions: control; antioxidant cocktail (α-lipoic acid, vitamins C and E); and prostaglandin inhibitor ingestion (ibuprofen). Ultrasound measurements of brachial artery responses were assessed throughout 5 min of forearm ischemia and 3 min after. Subsequently, an ischemia-reperfusion injury was induced by a 20-min upper arm occlusion. Further, vascular function protocols were completed at 15, 30, and 45 min of recovery. RESULTS: Endothelial dysfunction was evident in all conditions. FMD was attenuated at 15 min after ischemia-reperfusion injury (Pre: 6.24 ± 0.58%; Post15: 0.24 ± 0.75%; mean ± SD, P < 0.05), but recovered by 45 min. Antioxidant administration did not preserve FMD compared with control (P > 0.05). The magnitude of L-FMC was augmented at 15 min (Pre: 1.44 ± 0.27%; Post15: 3.75 ± 1.73%; P < 0.05) and recovered by 45 min. Ibuprofen administration produced the largest constrictive response (Pre: -1.13 ± 1.71%; Post15: -5.57 ± 3.82%; time × condition interaction: P < 0.05). CONCLUSION: Results demonstrate ischemia-reperfusion injury causes endothelial dysfunction and acute oral antioxidant supplementation fails to reduce its magnitude. Our results also suggest that a lack of shear stress during occlusion combined with suppression of prostaglandin synthesis magnifies L-FMC, possibly due to augmented endothelin-1 expression.

Dual effect of saikogenin D: in vitro inhibition of prostaglandin E2 production and elevation of intracellular free Ca2+ concentration in C6 rat glioma cells.

To clarify the pharmacological profile of saikogenin D, we examined the effect of saikogenin D on prostaglandin E2 (PGE2) production and intracellular free Ca2+ concentration ([Ca2+]i) in C6 rat glioma cells. Saikogenin D (1-20 microM) inhibited PGE2 production induced by the Ca2+ ionophore A23187 in a concentration-dependent manner with the IC50 of about 3 microM. Saikogenin D did not affect the conversion of arachidonic acid into PGE2 in microsomal preparations. On the other hand, saikogenin D elevated [Ca2+]i in a concentration-dependent manner (10-100 microM) with the EC50 value of about 35 microM in the presence or absence of extracellular Ca2+. These results suggest that saikogenin D possesses a dual effect: an inhibition of A23187-induced PGE2 production without a direct inhibition of cyclooxygenase activity; and an elevation of [Ca2+]i that is attributed to Ca2+ release from intracellular stores.

Failure of dietary bentonite clay, Silent Herder mineral supplement, or parenteral Banamine to alleviate locoweed toxicosis in rats.

To evaluate treatments purportedly beneficial for livestock grazing locoweeds (LW), growing rats were fed diets containing 10 or 20% whole-plant Oxytropis sericea (LW) with and without Silent Herder mineral mix (1.5% of diet) or bentonite clay (1.5% of diet). Pregnant female rats fed 10% LW were treated i.m. with Banamine (a prostaglandins suppressor) or saline. The LW contained swainsonine (430 micrograms/g DM) and elicited toxicosis within 10 d at intake of 2 mg/kg BW. In Trial 1, 96 immature male Sprague-Dawley rats (BW approximately 100 g) were fed commercial rat feed (CRF) with and without LW, as follows: 100% CRF, free choice; 100% CRF, restricted intake to equal average intake of rats consuming 10 and 20% LW; 90% CRF+10% LW free choice; and 80% CRF+20% LW free choice. Diets with LW contained either no supplement or supplemental mineral mixture (Silent Herder, 1.5% of diet) or added bentonite clay (1.5% of diet). Twelve rats received each of eight dietary regimens through 28 d. Locoweed depressed (P < .05) feed intake and BW gain, increased (P < .05) relative size of liver, kidneys, heart, spleen, and testes, and altered blood serum components (P < .05) indicating toxicosis. Dietary provision of Silent Herder or bentonite failed to benefit rats that ingested approximately 4 or 8 mg of swainsonine/kg BW daily through 28 d. In Trial 2, 68 young adult female Sprague-Dawley rats (approximately 230 g BW) were mated and directly assigned to three diets (100% CRF, free choice, 100% CRF, intake restricted slightly below average intake of diet by rats consuming LW, or 90% CRF+10% LW free choice) and two treatments (i.m. saline or i.m. Banamine at .25 mg/kg BW daily for 10 d) in a 3 x 2 factorial arrangement. Approximately half (31 of 68) of the impregnated rats were killed at d 10, when Banamine was discontinued, but diets were continued until the remaining females gave birth. Ingested LW provided approximately 2 mg swainsonine/kg BW daily and elicited toxicosis in 10 d, but LW failed to affect numbers of live concepti at d 10 (P > .5) or numbers of offspring at parturition (P > .10). Banamine did not alleviate LW toxicosis of dams (P > .10). Provision of Silent Herder or bentonite in the diet or Banamine i.m. had no benefit for rats fed toxic locoweed.

Nonsteroidal anti-inflammatory drugs as adjuncts in the management of periodontal diseases and peri-implantitis.

For the past three decades, prostaglandin E2 and other arachidonic acid metabolites have been recognized as important proinflammatory mediators in bone resorption and various forms of periodontal disease. Nonsteroidal anti-inflammatory drugs are chemical compounds that selectively inhibit the synthesis of metabolites of the cyclooxygenase pathway, thereby blocking the production of prostaglandins, thromboxane, and prostacyclin. Inhibiting prostaglandin E2 synthesis with nonsteroidal anti-inflammatory drugs has been unequivocally shown in both animal and human studies to be of primary therapeutic efficacy. Recent lines of nonsteroidal anti-inflammatory drugs research have focused on the development of daily topical administration forms such as gels, toothpastes, and rinses. Furthermore, new studies have implicated prostaglandin E2 in the peri-implantitis process, opening the possibility to manage failing implants with topical nonsteroidal anti-inflammatory drug delivery systems.

Evaluation of anti-inflammatory and analgesic properties of L-glutamine.

It was established that L-glutamine, an aminoacid, has marked anti-inflammatory activity and moderate analgesic activity. The drug was effective orally in suppressing various experimentally induced inflammatory reactions and did not show any gastric irritation in anti-inflammatory doses. It is observed that the anti-inflammatory effect of L-glutamine is not due to counter irritant action. It is suggested that it may partially mediate its anti-inflammatory activity by interfering with the action and/or synthesis of prostaglandins. Its anti-inflammatory activity is comparable to that of phenylbutazone and merits further study.