1 In vitro and in vivo studies have demonstrated a dysfunctional nitrergic system in diabetes mellitus, thus explaining the origin of diabetic impotence. However, the mechanism of this nitrergic defect is not understood. 2 In the penises of streptozotocin (STZ)-induced diabetic rats, here, we show by immunohistochemistry that nitrergic nerves undergo selective degeneration since the noradrenergic nerves which have an anti-erectile function in the penis remained intact. 3 Nitrergic relaxation responses in vitro and erectile responses to cavernous nerve stimulation in vivo were attenuated in these animals, whereas noradrenergic responses were enhanced. 4 Activity and protein amount of neuronal nitric oxide synthase (nNOS) were also reduced in the penile tissue of diabetic rats. 5 We, thus, hypothesized that NO in the nitrergic nerves may be involved in the nitrergic nerve damage, since only the nerves which contain neuronal NO synthase underwent degeneration. 6 We administered an inhibitor of NO synthase, N G -nitro-L-arginine methyl ester (L-NAME), in the drinking water of rats for up to 12 weeks following the establishment of diabetes with STZ. 7 Here we demonstrate that this compound protected the nitrergic nerves from morphological and functional impairment. Our results show that selective nitrergic degeneration in diabetes is NOdependent and suggest that inhibition of NO synthase is neuroprotective in this condition.
Onchocerciasis (river blindness) is a serious health problem and a severe obstacle to social and economic development, especially in Africa. A complementary DNA fragment coding for an Onchocerca volvulus antigen (OV-16) was cloned and expressed in the plasmid vector pCG808fx. Immune responses to this O. volvulus-specific recombinant antigen were detectable in patients with documented onchocerciasis; the antibody response was also detectable at 3 months and at more than 1 year before infection could otherwise be detected in humans and in chimpanzees experimentally infected with O. volvulus third-stage larvae.
Improved methods are needed for field diagnosis of onchocerciasis, to support efforts aimed at elimination of the disease. A rapid-format card test was evaluated that detects IgG4 antibodies to recombinant Onchocerca volvulus antigen Ov16 with serum samples from patients with onchocerciasis and with various types of control serum samples. The sensitivity of the test with serum samples from 106 microfilariae-positive subjects was 90.6%. The test was equally sensitive with serum samples obtained from patients in Africa and Latin America. Specificity was excellent; positive tests were observed for 2 of 38 serum samples from patients with other filarial infections and for 1 of 23 serum samples from patients with nonfilarial helminth infections. The 3 "false-positive" serum samples were from West Africans who could have been coinfected with onchocerciasis. No positive tests were observed with nonendemic serum samples from normal adults, patients with autoimmune disorders, or patients with the hyper-IgE syndrome. This new test holds great promise as a simple tool for diagnosis of onchocerciasis.
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