ABSTRACT
Evidence, even if not univocal, of increase of systolic and diastolic blood pressure for Pb doses lower than 30 microg/dl stimulated studies in the last years and opened a discussion on a possible relapse in morbility and mortality, since hypertension is an important factor of cardiovascular risk. In this study, it was possible to investigate the relationship between lead and blood pressure of 303 subjects occupationally exposed to this metal with blood-Pb between 10 and 80 microg/dl and 206 subjects belonging to the general population with blood-Pb between 0.5 and 9 microg/dl. In both groups it resulted a positive and statistically significant correlation between blood-Pb values and systolic and diastolic blood pressure values, in detail in hypertensive subjects, belonging to the not-occupationally exposed group, this effect is proportionally higher. The effect of lead on blood pressure appears therefore proved, as confirmed by previous literature, but taking into consideration three specific information. It presents itself in a large range of doses, it is quantitatively very modest, it appears more evident at low doses, thus we could hypothesize different mechanisms for different doses.
Subject(s)
Blood Pressure/drug effects , Lead/pharmacology , Occupational Exposure , Adult , Humans , Lead/metabolism , MaleABSTRACT
UNLABELLED: Neuropathic pain is a significant clinical problem. Currently, there are no drugs that produce complete amelioration of this type of pain. We have previously shown that KRN5500, a derivative of the antibiotic spicamycin, produces a prolonged (7-day), and significant reduction in neuropathic pain, but not nociceptive pain. Herein, we provide further evidence for the efficacy of this drug in inhibiting pain after IV injection in a spared nerve injury model of neuropathic pain. A single IV dose of the drug produces an increase in pain thresholds to punctuate mechanical stimuli and to cold stimuli over a period of 7 days, whereas IV injection of the vehicle is without any effect. No change in pain threshold was observed in the contralateral foot. In addition, a significant antiallodynic effect to mechanical stimuli was observed at 1, 2, 4, and 6 wk. The drug may be a potential candidate for cancer-related neuropathic pain as well as a marker for discovery of effective analgesics for neuropathic pain. IMPLICATIONS: We examined the effect of a novel drug (KRN5500) on nerve damage pain. After the successful effects of this drug in a single human, we have shown that the drug infused as a single application at different doses in a rat model of nerve damage pain produces pain relief in this model for many weeks.
Subject(s)
Neurons, Afferent/drug effects , Pain/drug therapy , Peripheral Nervous System Diseases/drug therapy , Purine Nucleosides/pharmacology , Animals , Cold Temperature , Hyperalgesia/physiopathology , Male , Neurons, Afferent/pathology , Pain/pathology , Pain Threshold/drug effects , Peripheral Nervous System Diseases/pathology , Physical Stimulation , Rats , Rats, Sprague-Dawley , Weight Gain/drug effectsABSTRACT
The goal of this study was to examine the effects of synthetic spicamycin derivative, SAN-Gly, on mechanical allodynia in a spared nerve injury animal model of neuropathic pain. Adult male rats underwent surgical ligation and cutting of the common peroneal and tibial nerves, which produced a mechanical allodynia within 2-4 days. One week after the surgery, SAN-Gly was administered via intravenous injection. Mechanical allodynia was measured using von-Frey hairs. Spicamycin produced a significant reduction in mechanical allodynia for up to 6 weeks. This study demonstrates that SAN-Gly may be of potential use in treating patients with neuropathic pain.
