Endogenous brain Na pumps, brain ouabain-like substance and the alpha2 isoform in salt-dependent hypertension.

An endogenous ouabain-like substance (OLS) plays a critical role in the etiology of experimental models of human hypertension induced by a high salt diet. Early on, evidence for a role of this Na, K-ATPase inhibitor in blood pressure regulation was provided mainly by correlations of blood pressure with the levels of circulating Na, K-ATPase inhibitor. However, over the past decade, numerous studies have shown that endogenous Na pump inhibitors in the brain mediate salt-dependent hypertension in a variety of experimental models, including Dahl salt-sensitive (Dahl-S) and spontaneously hypertensive (SHR) rats on a high-salt diet. Other forms of hypertension that are known to be mediated by endogenous ouabain-like substances include steroid/salt- (e.g., DOCA-salt) and ACTH-induced hypertension. Even when exogenous ouabain is peripherally administered and/or the plasma ouabain/OLS level is increased in rats, the resulting hypertension is of CNS origin. After peripheral ouabain administration, ouabain levels increase in the plasma and the inhibitor subsequently accumulates in the brain. The ensuing hypertension is abolished by the intracerebroventricular (icv) administration of an anti-ouabain antibody (but not by the same antibody dose given iv), by discrete excitotoxic lesions in the brain or by ganglionic blockade, demonstrating that the response is neurally mediated. The pressor response to stimuli that increase the brain OLS (high salt diet, icv sodium) or to icv ouabain is abolished by icv losartan, demonstrating that the brain OLS activates the brain renin-angiotensin system (RAS) downstream. There are three isoforms of the catalytic alpha subunit of the Na, K-ATPase in the brain and cardiovascular system (alpha1, alpha2 and alpha3), but it is not known which brain isoform(s) mediate the hypertensive effects of circulating/CNS ouabain. Preliminary studies in gene-targeted mice suggest that the alpha2 isoform plays a critical role.     

Tight nuchal cord and neonatal hypovolaemic shock.

Two neonates who went into acute hypovolaemic shock due to a tight nuchal cord were successfully resuscitated. The occurrence of this life threatening complication in two low risk pregnancies emphasises the importance of having staff trained in resuscitation immediately available in the delivery unit.     

Haemophilus ducreyi infection in south Florida: a rare disease on the rise?

Increased numbers of patients with genital ulcers sought medical attention in the Palm Beach County, Florida, Sexually Transmitted Disease clinics from Aug 1, 1982 to Aug 31, 1983. We established that a small proportion of subsequent cases of genital ulcers were caused by Haemophilus ducreyi, the etiologic agent associated with chancroid. We also set up a surveillance system to monitor this sexually transmitted infection, and have illuminated several recent cases of chancroid occurring in that area. This outbreak of chancroid suggest that clinicians practicing in south Florida consider chancroid (generally a rare disease in the United States) in their differential diagnoses of genital ulcers.     

Local cerebral glucose utilization during intracerebral pH changes

The effect of ventriculocisternal perfusion with mock CSF with alkaline or acidic pH on the local CMRglu (LCMRglu) in the caudatoputamen was studied in artificially ventilated and relaxed rats. In control rats both lateral cerebral ventricles were perfused with mock CSF at pH 7.4. In the experimental series one cerebral ventricle was infused with normal mock CSF while the other was infused with mock CSF in which the pH was decreased or increased by changing [HCO-3]. LCMRglu was depressed in acidotic brain tissue while it was strongly increased in alkalotic brain tissue. The importance of these alterations in brain glucose metabolism for the homeostatic regulation of brain pH is discussed.     

In vitro modulation of cisplatin cytotoxicity by sparsomycin inhibition of protein synthesis

Inhibition of protein synthesis can alter cellular responsiveness to the classical anticancer drugs. The in vitro response of Chinese hamster ovary (CHO) cells to cisplatin with or without sparsomycin (Sm) was studied with the use of [3H]leucine and [methyl-3H]thymidine incorporation and clonogenic assay. Pretreatment of exponentially growing CHO cells with 1 microgram Sm/ml for 3 or 5 hours decreased [3H]leucine incorporation by 20% and resulted in significant resistance to cisplatin (P = .005). Sm in a concentration of 10 micrograms/ml reduced [3H]leucine and [methyl-3H]thymidine incorporation after 3 hours by 92 and 84%, respectively, and resulted in potentiation of the cisplatin cytotoxicity (P = .004). This effect was the same in the case of nonproliferating cells (P = .005), while protection due to Sm (1 microgram/ml) was seen only during cell proliferation. Simultaneous incubation and postincubation with Sm proved to have much less or no potentiating effect on cisplatin. The mechanisms of both protection and potentiation are still not clear, but our data indicate that Sm is a promising drug for further studies on the modulation of the cancer cell response to classical anticancer drugs.