We investigated whether prior exposure to chronic wheel running (WR) alters maladaptive patterns of excessive and escalating methamphetamine intake under extended access conditions, and intravenous methamphetamine self-administration-induced neurotoxicity. Adult rats were given access to WR or no wheel (sedentary) in their home cage for 6 weeks. A set of WR rats were injected with 5-bromo-2′-deoxyuridine (BrdU) to determine WR-induced changes in proliferation (2-h old) and survival (28-day old) of hippocampal progenitors. Another set of WR rats were withdrawn (WRw) or continued (WRc) to have access to running wheels in their home cages during self-administration days. Following self-administration [6 h/day], rats were tested on the progressive ratio (PR) schedule. Following PR, BrdU was injected to determine levels of proliferating progenitors (2-h old). WRc rats self-administered significantly less methamphetamine than sedentary rats during acquisition and escalation sessions, and demonstrated reduced motivation for methamphetamine seeking. Methamphetamine reduced daily running activity of WRc rats compared with that of pre-methamphetamine days. WRw rats self-administered significantly more methamphetamine than sedentary rats during acquisition, an effect that was not observed during escalation and PR sessions. WR-induced beneficial effects on methamphetamine self-administration were not attributable to neuroplasticity effects in the hippocampus and medial prefrontal cortex, but were attributable to WR-induced inhibition of methamphetamine-induced increases in the number of neuronal nitric oxide synthase expressing neurons and apoptosis in the nucleus accumbens shell. Our results demonstrate that WR prevents methamphetamine-induced damage to forebrain neurons to provide a beneficial effect on drug-taking behavior. Importantly, WR-induced neuroprotective effects are transient and continued WR activity is necessary to prevent compulsive methamphetamine intake.
Cerebral venous sinus thrombosis may present with transient aphasia and focal seizure-like activity mimicking a TIA or stroke. In this case, the patient's presentation was further complicated by non-diagnostic CT findings, which can be common in up to 27% of cases [1].An 86-year-old right-handed male with a history of colon adenocarcinoma status post resection and recent surgery for right sphenoid wing meningioma presented to the ED with transient episodes of fluent aphasia lasting approximately 10 minutes and one episode of involuntary right-hand clenching, both of which resolved spontaneously and were concerning for possible TIA. Non-contrast head CT, CTA head and neck, and CT perfusion studies showed non-opacification of the left transverse and sigmoid sinuses, but no perfusion defects. Subsequent MRI brain with gadolinium revealed a new left transverse sinus thrombus. EEG was without epileptiform features. For the 13-day remainder of his hospitalization the patient received low molecular weight heparin for anticoagulation, and he experienced no recurrence of his symptoms. He was discharged on apixiban and levetiracetam to followup for possible tumor recurrence.Cerebral venous sinus thrombosis can present with stroke-like symptoms, and CT perfusion studies can be normal. CT venography, MRI with gadolinium, and MR venography are sensitive imaging modalities for diagnosing dural sinus thrombosis and should be considered, especially for patients with hypercoagulable risk factors, MR venography being the most sensitive, preferred modality [2]. Additionally, it is important to recall the laterality of focal symptoms, as a history of cerebrovascular disease can be a confounding factor in diagnosis.
The effect on renal function of a combination of a beta 2 receptors stimulating tokolytic agent (Fenoterol) with a so-called cardioselective beta 1 blocker (Metoprolol) which is able to antagonise the cardiac side effects of beta 2 stimulation, was examined in femaLe rabbits in a 24-hour test. Infusing 31.5 ml/h isotonic solution, 20 micrograms/kg/min Fenoterol and 3.125 micrograms/kg/min Metoprolol, excretion, creatinine clearance, electrolyte elimination, the serum electrolyte levels, Hb, HK and the weight were determined. The combination of Fenoterol and Metoprolol antagonised almost completely the massive water retention occurring under Fenoterol alone. At the latest after 12 hours, normal values were obtained in respect of the creatinine clearance reduced under Fenoterol, the urine excretion rate and, consequently, the Hb concentration and haematocrit reading. The reduction of sodium elimination caused by Fenoterol was completely reversed under the combination, whereas the reduced excretion of potassium was not influenced. Water retention in tocolysis with beta 2 stimulants is one of the most important causes for the information of a pulmonary oedema. The danger of the occurrence of such pulmonary oedemas, especially in risk pregnancies (gestosis), is drastically reduced by antagonising water retention, and hence the combination of Fenoterol and Metoprolol seems to be very favourable from both the cardiac and renal viewpoints. In a group of 17 pregnant women, the drastic improvement of urine excretion under the combination could be confirmed.
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