The revolution that wasn't: a new interpretation of the origin of modern human behavior.

Background Cardiac troponin T is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. We used a newly developed enzyme immunoassay for troponin T to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. Methods We screened 109 patients with unstable angina (25 with accelerated or subacute angina and 84 with acute angina at rest) for serum creatine kinase activity, creatine kinase isoenzyme MB activity, and troponin T every eight hours for two days after admission to the hospital. The outcomes of interest during the hospitalization were death and myocardial infarction. Results Troponin T was detected (range, 0.20 to 3.64 micrograms per liter; mean, 0.78; median, 0.50) in the serum of 33 of the 84 patients (39 percent) with acute angina at rest. Only three of these patients had elevated creatine kinase MB activity (two were positive for troponin T, and one was negative). Of the 33 patients who were positive for troponin T, 10 (30 percent) had myocardial infarction (3 after coronary-artery bypass surgery), and 5 of these died during hospitalization. In contrast, only 1 of the 51 patients with angina at rest who were negative for troponin T had an acute myocardial infarction (P less than 0.001), and this patient died (P = 0.03). Thus, 10 of the 11 patients with myocardial infarctions had detectable levels of troponin T; only 1 had elevated creatine kinase MB activity. Troponin T was not detected in any of the 25 patients with accelerated or subacute angina, and none of these patients died. Conclusions Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial-cell injury than serum creatine kinase MB activity, and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina.

https://www.nejm.org/doi/pdf/10.1056/NEJM199207163270302

The prognostic value of serum troponin T in unstable angina.

Isozymes of the Na+/K+-ATPase.

Histochemical studies from our (Williams & Felten 1981, Williams et al. 1981, D. Felten et al. 1981, 1984, 1985, 1987a, 1987b, Livnat et al. 1985, Ackerman et al. 1986, S. Felten et al. 1987) and other laboratories (Giron et al. 1980, Bulloch & Pomeranz, 1984, Singh 1984, Walcott & MacLean 1985) have shown the presence of autonomic nerve fibers in specific compartments of both primary and secondary lymphoid organs. These nerve fibers are associated not only with blood vessels but also with lymphocytes and macrophages. We have demonstrated that the neurotransmitter norepinephrine (NE), present in the postganglionic sympathetic fibers that richly innervate lymphoid organs, acts in the spleen as both a paracrine secretion, available to receptors on cells in the white pulp, and a localized neurotransmitter in nerve terminals that directly contact T lymphocytes in the periarteriolar lymphatic sheath (PALS) (S. Felten et al. 1986, S. Felten & Olschowka 1987). We propose that NE in lymphoid organs fulfills the criteria for neurotransmission, estabUshed in more traditional efTector tissues such as the heart, and plays a role in the modulation of immune responses. This review summarizes evidence for neurotransmission, including presence and compartmentation of NE, transmitter release, post-synaptic receptors on cells of the immune system, and functional consequences of denervation and pharmacological manipulation of NE. We also review aspects of development, aging, and plasticity of noradrenergic (NA) fibers that enhance our understanding of their role in organs of the immune system.

Noradrenergic sympathetic neural interactions with the immune system: structure and function.

Vanadium compounds exert preventive effects against chemical carcinogenesis on animals, by modifying, mainly, various xenobiotic enzymes, inhibiting, thus, carcinogen-derived active metabolites. Studies on various cell lines reveal that vanadium exerts its antitumor effects through inhibition of cellular tyrosine phosphatases and/or activation of tyrosine phosphorylases. Both effects activate signal transduction pathways leading either to apoptosis and/or to activation of tumor suppressor genes. Furthermore, vanadium compounds may induce cell-cycle arrest and/or cytotoxic effects through DNA cleavage and fragmentation and plasma membrane lipoperoxidation. Reactive oxygen species generated by Fenton-like reactions and/or during the intracellular reduction of V(V) to V(IV) by, mainly, NADPH, participate to the majority of the vanadium-induced intracellular events. Vanadium may also exert inhibitory effects on cancer cell metastatic potential through modulation of cellular adhesive molecules, and reverse antineoplastic drug resistance. It also possesses low toxicity that, in combination with the synthesis of new, more potent and better tolerated complexes, may establish vanadium as an effective non-platinum, metal antitumor agent.

/pdf/vanadium-in-cancer-treatment-2tbgtbwiwz.pdf

Vanadium in cancer treatment.

MANY samples hf ‘Sigma grade’ ATP from Sigma Chemical Co. reportedly contained an impurity which induces anomalous kinetics of (Na, K)-ATPase activity1–3. This impurity has recently been identified as vanadate4, and shown to inhibit (Na, K)–ATPase from kidney4 and red blood cells5. These findings have received considerable interest because of a possible physiological role of vanadate as an endogenous regulator of (Na, K)–ATPase activity3–5. We now report that vanadate is capable of producing positive inotropic effects in electrically driven papillary muscles isolated from cats.

Positive inotropism of vanadate in cat papillary muscle.

Vanadate and its significance in biochemistry and pharmacology

Vanadium compounds have been reported to inhibit the (Na+ + K+)ATPase activity of several cell membrane preparations1–3, to have a positive inotropic effect on ventricular cardiac muscle4, slightly increase myocardial cyclic AMP levels5, stimulate fat cell adenylate cyclase6, and cause natriuresis in rats7. Recently we have reported that vanadate produces a transient, initial stimulation of (Na+ + K+) ATPase activity in a cat heart cell membrane preparation, in addition to its well known inhibitory action on this enzyme system8. The transient stimulation occurred at the same concentration range as did the inotropic effects. There was, however, a serious discrepancy between the time courses of the two events. The former lasted only a few minutes, whereas the latter remained virtually stable for at least 30 min. The supposed stimulatory action of vanadate on (Na+ + K+)ATPase was deduced from an initial rapid loss of NADH in the ATPase assay used (optical coupled assay with an ATP regenerating system9). The oxidation of NADH was followed photometrically by continuous recording8. We now report that the rapid loss of NADH and hence the claimed transient stimulatory action of high concentrations of vanadate on the (Na+ + K+)ATPase activity is caused rather by an oxidation of NADH as a result of a NADH-dependent reduction of vanadate.

Purified cardiac cell membranes with high (Na + + K + ) ATPase activity contain significant NADH-vanadate reductase activity

The occurrence of unstable angina pectoris, despite medical treatment, is generally regarded as an ominous prognostic sign and an indication for invasive diagnosis and revascularization. We investigated 38 consecutive patients with severe unstable angina with a mean of 2.5 days of continuous two-channel, frequency modulated Holter monitoring for ST segment analysis. In 16 patients, transient ischaemic episodes (more than 0.1 mV lasting more than 1 min) occurred despite maximal medical treatment: 82% of the episodes were silent. Compared to the 22 patients without ischaemic episodes there were no significant differences in prevalence of risk factors, numbers of vessels diseased (69% vs. 74% triple-vessel disease) or ejection fraction (54±15% vs. 53±16%). The 30-day prognosis, however, varied: of 16 patients with ischaemic episodes, 14 (88%) had a subsequent cardiac event (death, AMI, PTCA or CABG) compared to only 10 of 22 patients (45%) without ischaemic episodes (P < 0.02 for all events, P <0.1 for death/ AMI only).

Transient ischaemic episodes, predominantly silent, are frequent in patients with severe unstable angina. Objective evidence of ongoing ischaemia despite medical treatment has a guarded short-term prognosis. ‘Stabilization’ of unstable angina may be incomplete as long as transient ischaemia at rest can still be detected.

Prognostic implications of transient — predominantly silent — ischaemia in patients with unstable angina pectoris

Effects of vanadate in cultured rat heart muscle cells. Vanadate transport, intracellular binding and vanadate-induced changes in beating and in active cation flux

W. Krawietz

Papers

Positive inotropism of vanadate in cat papillary muscle.

Vanadate and its significance in biochemistry and pharmacology

Purified cardiac cell membranes with high (Na + + K + ) ATPase activity contain significant NADH-vanadate reductase activity

Prognostic implications of transient — predominantly silent — ischaemia in patients with unstable angina pectoris

Effects of vanadate in cultured rat heart muscle cells. Vanadate transport, intracellular binding and vanadate-induced changes in beating and in active cation flux