Lysophosphatidylcholine inhibits relaxation of rabbit abdominal aorta mediated by endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor independent of protein kinase C activation.

Hypercholesterolemia is associated with increased oxidized LDL and impaired endothelium-dependent relaxation (EDR). An inhibitory component of oxidized LDL is lysophosphatidylcholine (LPC). To determine the effect and mechanism(s) of action of LPC on EDR mediated by endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF), rabbit abdominal aortic rings were suspended for measurement of isometric tension and studied under three conditions: control; with 25 mmol/L K+ buffer to isolate relaxation mediated by EDNO; and in rings treated with N omega-nitro-L-arginine methyl ester (L-NAME, 30 mumol/L) to isolate relaxation mediated by EDHF. Incubation with LPC (10 and 30 mumol/L) for 30 minutes inhibited EDR in a concentration-dependent manner. LPC (30 mumol/L) significantly inhibited maximal relaxation to acetylcholine in control, 25 mmol/L K(+)-, and L-NAME-treated rings (77.1 +/- 7.8%, 42.1 +/- 8.9%, and 3.4 +/- 7.7%) compared with untreated rings (99.0 +/- 0.9%, 90.9 +/- 2.2%, and 54.7 +/- 4.7%, P < .05). Inhibition of relaxation was specific to endothelium-dependent responses in that relaxation to direct smooth muscle vasodilators (papaverine, 8-bromo-cGMP, and sodium nitroprusside) were unaltered by LPC. The inhibition by LPC (30 mumol/L) was not due to cytotoxicity, because EDR returned to normal levels after repeated washing with physiological salt solution containing 0.1% albumin. Co-incubation with protein kinase C inhibitors, staurosporine (20 nmol/L) or calphostin C (1 mumol/L), had no effect on the EDR inhibition by LPC (30 mumol/L). Furthermore, LPC continued to inhibit EDR in rings in which protein kinase C was down-regulated by incubation for 18 hours with 1 mumol/L phorbol 12-myristate 13-acetate (PMA).(ABSTRACT TRUNCATED AT 250 WORDS)

4-(Heteroarylthio)-2-biphenylyltetrazoles as nonpeptide angiotensin II antagonists.

A series of 4-(heteroarylthio)-2-biphenylyltetrazoles was prepared, and the compounds were examined for their ability to displace [3H]AII from angiotensin II receptors. Analogues that exhibited significant receptor binding affinities at less than 10 microM were investigated further for potential antagonism of angiotensin II-mediated contraction of rabbit isolated aortic rings. Three 4-(heteroarylthio)-2-biphenylyltetrazoles were identified that exhibited sub-micromolar angiotensin II receptor binding affinities. These compounds and two reference agents, saralasin and losartan (DUP-753), exhibited concentration-dependent reversal of angiotensin II contraction in isolated aortic rings parallel to their receptor binding affinities. Molecular modeling studies were conducted to examine the conformational effects of the novel sulfide bridging unit contained in these 4-(heteroarylthio)-2-biphenylyltetrazoles. The biological effects of the sulfide bridge as well as alterations in the heteroaromatic moiety were investigated, and the resulting structure--activity relationships are discussed.

Consumer product-related ocular trauma.

Leading causes of consumer product-related ocular trauma have not been well described. To delineate these causes in a nationally representative sample, data collected by the US Consumer Product Safety Commission (USCPSC) were reviewed. Data were obtained from the National Electronic Injury Surveillance System (NEISS), a national probability sample survey conducted by USCPSC that continuously monitors consumer product-related injuries treated in hospital emergency rooms across the United States. These data formulated the product summary report for the calendar year 1991. The sampling frame for the NEISS consisted of hospitals listed on the Center for Health Statistics Master Inventory File stratified geographically by size of hospital and number of emergency-room visits. During the calendar year 1991, there were a nationally estimated 298,852 consumer product-related eye injuries treated in hospital emergency rooms. Appoximately 500 different products were implicated in these injuries, with the leading cause being contact lenses (hard and soft), accounting for an estimated 26,490 emergency-room visits. This is followed by welding equipment (12,771 visits), hair curlers/curling irons (5946 visits), and workshop power grinders (5476 visits). Consumer products account for a sizable number of ocular injuries requiring treatment in hospital emergency rooms. Research on outcomes and prevention strategies of the injuries is warranted.

Diagnosis of reactive lymphoid hyperplasia by chorioretinal biopsy.

We treated a patient with reactive lymphoid hyperplasia in whom the diagnosis was made by chorioretinal biopsy. Histopathologic examination and culture of the biopsied specimen allowed us to rule out a neoplastic or infectious process. The biopsy result allowed us to treat him with systemic corticosteroid alone, thus avoiding the potential harmful side effects of other medications, including antituberculous drugs. There were no surgical or postoperative complications. This study confirms the usefulness of chorioretinal biopsy for establishing a diagnosis and formulating a rational treatment plan.

Enhanced role of potassium channels in relaxations to acetylcholine in hypercholesterolemic rabbit carotid artery.

The effect of hypercholesterolemia for 10 wk on endothelium-dependent relaxations to acetylcholine was studied in isolated rings of rabbit carotid artery and abdominal aorta contracted with phenylephrine or elevated potassium. In these arteries obtained from hypercholesterolemic rabbits, endothelium-dependent relaxations to acetylcholine were not significantly different from those of normal rabbits. In normal and hypercholesterolemic arteries, partial relaxation persisted in the presence of NG-nitro-L-arginine methyl ester (L-NAME), which blocked acetylcholine-induced increases in arterial guanosine 3',5'-cyclic monophosphate (cGMP). Combined treatment with L-NAME and the calcium-dependent potassium-channel inhibitor, charybdotoxin, blocked relaxations in both groups, suggesting that L-NAME-resistant relaxations are mediated by an endothelium-derived hyperpolarizing factor. Charybdotoxin alone or depolarizing potassium had no significant effect on normal carotid artery or normal and hypercholesterolemic abdominal aorta but significantly inhibited relaxations of the carotid artery from cholesterol-fed rabbits. The enhanced role of calcium-dependent potassium channels and the hyperpolarizing factor in relaxation of the hypercholesterolemic carotid artery suggested by these results was likely related to the fact that acetylcholine failed to stimulate cGMP only in that artery. These data suggest that endothelium-dependent relaxation in these rabbit arteries is mediated by nitric oxide-cGMP-dependent and -independent mechanisms. In hypercholesterolemia, the contribution of nitric oxide-cGMP in the carotid artery is reduced, but a hyperpolarizing factor and calcium-dependent potassium channels maintain normal acetylcholine-induced relaxation.

Potassium channel-mediated relaxation to acetylcholine in rabbit arteries.

Endothelium-dependent relaxation is associated with smooth muscle hyperpolarization in many arteries which may account for relaxation that persists in the presence of nitric oxide inhibitors such as NG-nitro-L-arginine methyl ester (L-NAME). Acetylcholine (ACh)-induced relaxations of the rabbit thoracic and abdominal aorta and iliac and carotid arteries were studied for the relative contribution of nitric oxide-dependent and -independent mechanisms in rings suspended for measurement of isometric tension. Although relaxation of the thoracic aorta to ACh (10(-6) M) was almost blocked completely by L-NAME (3 x 10(-5) M), the maximal relaxation in the abdominal aorta, carotid and iliac arteries was only reduced by 28, 26 and 62%, respectively. In rings of abdominal aorta, L-NAME blocked the ACh-stimulated (10(-6) M) rise in cyclic GMP verifying that relaxation which persists in L-NAME-treated rings is not mediated by nitric oxide. The L-NAME resistant response was nearly abolished by elevated external K+ in rings of abdominal aorta and carotid artery, suggesting this relaxation may be mediated by a membrane potential sensitive mechanism. Furthermore, tetraethylammonium (10(-3) M) partially and charybdotoxin (5 x 10(-8) M) completely inhibited the remaining L-NAME-resistant relaxation in both abdominal aorta and carotid artery, suggesting a role for Ca(++)-activated K(+)-channels. Blockers of ATP-sensitive K+ channels also inhibited the L-NAME resistant relaxation in the abdominal aorta only.(ABSTRACT TRUNCATED AT 250 WORDS)

Light hazards in the operating room.

The use of high-intensity illumination devices is routine for many ophthalmic diagnostic and therapeutic procedures. However, the exposure of patients to high-level photic energy may be damaging even in the absence of visible abnormalities. Devices such as the operating microscope, indirect ophthalmoscope, and endoilluminator are capable of irradiances sufficient to cause retinal damage and should be used with a degree of restraint that reflects a recognition of their potential for phototoxicity.

Different mechanisms of relaxation of pig coronary artery to bradykinin and cromakalim are distinguished by potassium channel blockers.

Bradykinin relaxes porcine coronary artery in an endothelium-dependent manner that is not dependent on release of nitric oxide or cyclic GMP accumulation. The mechanism of this relaxation was investigated in rings of porcine coronary artery by comparing bradykinin-induced relaxation with that induced by cromakalim, an agent know to cause hyperpolarization mediated by potassium channels. Relaxation to bradykinin was determined in rings treated with methylene blue, indomethacin and captopril to inhibit cyclic GMP accumulation, prostaglandin formation and bradykinin degradation, respectively. Relaxation to cromakalim was inhibited by the potassium channel blockers glybenclamide (10(-6) M), tetraethylammonium (10(-2) M), quinine (3 x 10(-5) M) and procaine (5 x 10(-3) M), whereas barium (10(-4) M) and 4-amino-pyridine (10(-3) M) were without effect. None of these potassium channel blockers had any effect on the relaxation to bradykinin. These results suggest that relaxation of pig coronary artery to cromakalim is mediated by a mechanism sensitive to potassium channel blockers. Also, the mechanism of nitric oxide-independent relaxation to bradykinin is distinct from that of cromakalim.

Two mechanisms mediate relaxation by bradykinin of pig coronary artery: NO-dependent and -independent responses.

The role of nitric oxide and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in the endothelium-dependent relaxation of the porcine coronary artery to bradykinin was investigated by comparing relaxation and cGMP accumulation in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) and methylene blue. Rings were treated with indomethacin to eliminate the effects of prostaglandins. Relaxation to bradykinin of rings contracted with the thromboxane A2 mimetic U-46619 was not affected by L-NMMA and was only minimally inhibited by methylene blue. Rings contracted with elevated potassium (25 mM) also relaxed completely to bradykinin. However, L-NMMA or methylene blue effectively inhibited relaxation to bradykinin in rings contracted with potassium. cGMP accumulation was stimulated by bradykinin and inhibited by L-NMMA or methylene blue in rings contracted with either U-46619 or potassium. These results suggest that in the absence of nitric oxide-induced cGMP accumulation, a nonprostanoid mechanism exists that is capable of completely relaxing U-46619-contracted coronary artery. This mechanism is either inhibited in or unable to relax potassium-contracted rings. These results also demonstrate that nitric oxide mediates the bradykinin-induced cGMP accumulation that is largely responsible for the relaxation during contraction with potassium.

Cholinergic regulation of resting coronary blood flow in domestic swine.

Cholinergic vasoconstriction in vivo and the influence of resting cholinergic activity on basal coronary tone were investigated by measuring coronary blood flow, cardiac function, and blood gases during either acetylcholine injection, muscarinic receptor blockade, or vagal ligation, in open-chest chloralose-urethan-anesthetized swine. Intracoronary injections of acetylcholine (0.5-3.0 micrograms) caused significant (P less than 0.05) dose-dependent reductions in coronary blood flow (19.0-75.5%) and conductance (14.3-78.2%). Atropine (200 micrograms) completely blocked these responses. Cholinergic mediation of basal coronary tone was initially evaluated by determining the effects of muscarinic blockade with intracoronary injection of atropine (200 micrograms). Intracoronary injection of atropine had no significant effects on coronary blood flow or conductance. Finally, to ensure that parasympathetically released acetylcholine was not overcoming the muscarinic blockade, vagal ligation was performed during pacing. Neither coronary blood flow nor conductance was significantly altered by vagal ligation. The present studies demonstrate that acetylcholine induces a muscarinic vasoconstriction of coronary arteries in the domestic swine. However, these studies do not support a role for parasympathetic mediation of basal coronary vascular tone.

National survey of the prevalence and risk factors of glaucoma in St. Lucia, West Indies. Part I. Prevalence findings.

Although blacks appear to be at higher risk for blindness from glaucoma, there is little information available on the epidemiology of this disease in this population. Using a cluster sampling technique with systematic allocation of clusters, the authors conducted a national survey of black individuals 30 years of age and older, in St. Lucia. A total of 1679 individuals underwent a screening examination that included visual acuity, intraocular pressure (IOP) measurement, and cup/disc (C/D) evaluation. Every third person had a screening field on the Humphrey field analyzer. Individuals with either elevated IOP, abnormal C/D ratio, or an abnormal screening visual field were referred for a definitive examination and threshold visual fields. A total of 520 people were referred. Identified by stringent criteria for the diagnosis of glaucoma, which required reliable threshold visual fields abnormal by the mirror image method, 147 individuals had glaucoma for a prevalence of 8.8% in the 30 years of age and older population.

Pasteurella multocida corneal ulcer following a baseball injury.

Pasteurella multocida is an ubiquitous organism that can be isolated from a variety of animals and birds. It is an infrequent ocular pathogen but can cause infection as a result of injury or animal exposure. This article reports a case of P multocida corneal ulcer following a baseball injury.

Endogenous Bacillus cereus panophthalmitis.

Over the past seven years we have treated three cases of drug abusers in whom endogenous Bacillus cereus endophthalmitis rapidly progressed to panophthalmitis. Ocular features of infection with this organism include severe pain, chemosis, proptosis, corneal infiltration and ring abscess, subretinal exudation, retinal hemorrhages, and perivasculitis. The process becomes fulminant in an explosive manner and may be accompanied by fever and leukocytosis. Ophthalmologists should be cognizant of the apparent susceptibility of drug abusers to Bacillus cereus infections and should consider this organism in any severe, rapidly evolving intraocular infectious process.

When should sarcoidosis be treated?

About 80 percent of sarcoidosis cases are benign and do not require treatment, but 20 percent will have chronic unremitting disease for which therapy is essential. It is important that the physician identify this group and begin therapy promptly. If the disease is active, treat. If it is inactive, do not treat. Activity depends upon three major tests: serum angiotensin converting enzyme, gallium 67 scan, and bronchoalveolar lavage. The other consideration is involvement of vital organ systems; ie, active ocular disease, progressive pulmonary involvement as evidenced by increasing symptoms, impaired and deteriorating pulmonary function, or radiographic changes; hypercalcemia or hypercalciuria; central nervous system involvement; disfiguring cutaneous lesions; and myocardial sarcoidosis. Following a therapeutic decision to treat, adrenocorticoids are the drugs of choice. Methylprednisolone, prednisone, and cortisol are listed in order of benefit. Alternate day and/or low-dose steroids are increasing in popularity. Chloroquine phosphate is beneficial for skin lesions, while oxyphenbutazone has been found to be at least as effective as prednisone. Immunosuppressives may be used also. Chlorambucil and azathioprine have shown variable results. Cyclosporine (Cyclosporin A) shows promise and is now undergoing therapeutic trials.

Ocular disturbances in vitiligo.

One hundred fifty-six patients with vitiligo were examined for ocular abnormalities. A 2:3 ratio of white to black patients allowed us to evaluate the role of race in the occurrence of ocular disturbances. A large percentage (40%) of all patients showed some degree of fundal pigment disturbance including pigment clumps, focal hypopigmented spots, and choroidal nevi. Although racial variations were found in the incidence of choroidal nevi (p = 0.001) and iris transillumination (p = 0.0012), these variations were believed to reflect normal differences found in patients without vitiligo.