Metallic taste in cancer patients treated with chemotherapy.

BACKGROUND: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic taste in chemotherapy treated cancer patients. METHODS: Literature search for metallic taste and chemotherapy was performed in PubMed up to September 2014, resulting in 184 articles of which 13 articles fulfilled the inclusion criteria: English publications addressing metallic taste in cancer patients treated with FDA-approved chemotherapy. An additional search in Google Scholar, in related articles of both search engines, and subsequent in the reference lists, resulted in 13 additional articles included in this review. Cancer patient forums were visited to explore management strategies. FINDINGS: Prevalence of metallic taste ranged from 9.7% to 78% among patients with various cancers, chemotherapy treatments, and treatment phases. No studies have been performed to investigate the influence of metallic taste on dietary intake, body weight, and quality of life. Several management strategies can be recommended for cancer patients: using plastic utensils, eating cold or frozen foods, adding strong herbs, spices, sweetener or acid to foods, eating sweet and sour foods, using 'miracle fruit' supplements, and rinsing with chelating agents. INTERPRETATION: Although metallic taste is a frequent side effect of chemotherapy and a much discussed topic on cancer patient forums, literature regarding metallic taste among chemotherapy treated cancer patients is scarce. More awareness for this side effect can improve the support for these patients.

Methylazoxymethanol acetate-induced abnormalities in the entorhinal cortex of the rat; parallels with morphological findings in schizophrenia.

It has been suggested repeatedly that the non-heritable factors in the pathogenesis of schizophrenia involve abnormalities of prenatal neurodevelopment. Furthermore, post-mortem studies show neuropathology of apparently developmental origin in the entorhinal cortex and other brain regions of schizophrenic subjects. In an attempt to model a developmental defect of the entorhinal region in the rat, cerebrocortical proliferation was briefly interrupted during its earliest stages, when the entorhinal area is thought to undergo major cell division. Specifically, the experimental set-up involved the administration of methylazoxymethanol acetate (MAM) on 1 of 4 consecutive days of embryonal development, from E9 to E12. Analysis of the forebrain in adult animals shows reduction of the entorhinal cortex in rats treated on each of these days. This effect shifts from lateral to medial divisions of the entorhinal cortex with later administration of MAM, following a known developmental gradient. Morphological consequences of MAM administration appear to be largely confined to the entorhinal cortex in the groups treated on E9 to E11, although slight reductions of the frontal and occipital neocortex were also observed in these animals. MAM treatment on E12 produces relatively more widespread damage, as reflected among other in a small reduction of brain weight. The described brain abnormalities are not accompanied by obvious phenotypical changes in any, but the E12-treated group. They, moreover, involve cortical thinning, disorganised cortical layering, and abnormal temporal asymmetries. These finding bare some similarity to observations in brains of schizophrenic subjects. The possible relevance of this approach in modeling neurodevelopmental aspects of schizophrenia is discussed.

Angina pectoris refractory for conventional therapy--is neurostimulation a possible alternative treatment?

The treatment of angina pectoris as a symptom of coronary artery disease usually is focused on restoring the balance between oxygen demand and supply of the myocardium by administration of drugs interfering in heart rate, cardiac pre- and afterload, and coronary vascular tone. For nonresponders to drug therapy or for those with jeopardized myocardium, revascularization procedures such as coronary bypass surgery and percutaneous transluminal coronary angioplasty are at hand. However, the atherosclerotic process is not stopped by these therapies and, at longer terms, angina may recur. It is not always possible to revascularize all the patients who do not positively react to medical treatment. Those with angina, not responding to adequate medication and who are not suitable anymore for revascularization, are considered to suffer from refractory angina pectoris. This group of patients has a poor quality of life, for their exercise tolerance is severely afflicted. For these patients, neurostimulation has been described repeatedly as an effective and safe therapy. The mechanism of action of neurostimulation is not completely known, but recent studies suggest an anti-ischemic effect, exerted through changes in myocardial blood flow. As soon as its safety is sufficiently established, it may become a useful alternative in the treatment of refractory angina pectoris.

L-deprenyl reduces brain damage in rats exposed to transient hypoxia-ischemia.

BACKGROUND AND PURPOSE: L-Deprenyl (Selegiline) protects animal brains against toxic substances such as 1-methyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine. Experiments were conducted to test whether L-deprenyl prevents or reduces cerebral damage in a transient hypoxia/ischemia rat model. METHODS: Rats were treated for 14 days with 2 mg/kg and 10 mg/kg L-deprenyl or saline. After surgery a 20-minute hypoxia/ischemia period was induced by simultaneous occlusion of the left common carotid artery and reduction of the percentage of oxygen in the gas mixture to 10%. Rats were killed 24 hours later. Silver staining was used to reveal damage in several brain regions. RESULTS: In the brain, both L-deprenyl dosages reduced damage up to 78% compared with the controls. Total brain damage was decreased from 23%-31% to 5%-9% with the L-deprenyl treatment (2 mg/kg: F1.13 = 6.956, P < .05; 10 mg/kg: F1.13 = 5.731, P < .05). In the striatum, significant treatment effects were found between both the L-deprenyl groups (2 mg/kg and 10 mg/kg, respectively) and the saline group (F1.13 = 14.870, P < .005; and F1.13 = 8.937, P = .01; respectively). In the thalamus, significant treatment effects were seen in the 2-mg/kg L-deprenyl group (F1.13 = 11.638, P < .005) and the 10-mg/kg group (F1.13 = 8.347, P < .05) compared with the control group. No significant damage decrease was seen in the hippocampus and the cortex. CONCLUSIONS: The results show that L-deprenyl is effective as a prophylactic treatment for brain tissue when it is administered before hypoxia/ischemia. Mechanisms responsible for the observed protection remain unclear. The regional differences in damage, however, are in accordance with the reported regional increase in superoxide dismutase and catalase activities after L-deprenyl treatment, suggesting the involvement of free radicals and scavenger enzymes.

Neurochemical lesioning in the rat brain with iontophoretic injection of the 1-methyl-4-phenylpyridinium ion (MPP+).

Iontophoretic injections of the 1-methyl-4-phenylpyridinium ion (MPP+) were made in the dopaminergic part of the substantia nigra to see whether this injection technique could be used for inducing localized neurochemical lesions in dopaminergic cell groups and to assess the effects of MPP+ on non-dopaminergic neurons. Three days after the iontophoretic injection of MPP+, a gliosis or necrotic hole was found in the dopaminergic and non-dopaminergic target areas. This effect depended on the injection parameters that were used; iontophoretic injections of short duration (less than or equal to 3 minutes) and low current strength (1.5 microA) caused the gliosis, higher injection parameters gave lesions. The estimated injected amount of MPP+ was between 0.5 and 10.8 nmol. Control injections, with sodium iodide, sodium chloride or N-methylpyridinium iodide showed that the neurodegeneration is not a side-effect of the iontophoretic injection procedure. It is concluded that iontophoretically injected MPP+ is toxic for all neurons, irrespective of the neurotransmitter used, and also for glia cells and fibers of passage. Excessive formation of free radicals, causing induction of lipid peroxidation, may be involved in the neurodegenerative process observed.

Ascending projections from the solitary tract nucleus to the hypothalamus. A Phaseolus vulgaris lectin tracing study in the rat.

The course of the ascending pathways originating from the anterior gustatory and posterior visceral sensory part of the solitary tract nucleus and the topographic organization of the projections to the hypothalamus in the rat were studied with anterogradely transported Phaseolus vulgaris lectin. In general, the posterior visceral sensory part of the solitary tract nucleus has ascending projections as far as the septum-diagonal band complex and gives rise to heavy input to the bed nucleus of the stria terminals, and to the dorsomedial and paraventricular hypothalamic nuclei. A more moderate projection is aimed at a variety of other hypothalamic nuclei, to the medial and central amygdaloid nuclei and to the paraventricular nucleus of the thalamus. The ventromedial hypothalamic nucleus is strikingly missing an afferent input from the nucleus of the solitary tract. Furthermore, it was shown that whereas the caudal solitary tract nucleus has predominant long ascending connections, the projections from the anterior taste related region of the nucleus of the solitary tract have only limited forebrain projections which do not reach beyond the level of the anterior dorsal hypothalamic nucleus.

Phaseolus vulgaris leuco-agglutinin tracing of intrahypothalamic connections of the lateral, ventromedial, dorsomedial and paraventricular hypothalamic nuclei in the rat.

Intrahypothalamic connections of the lateral (LHA), ventromedial (VMH), dorsomedial (DMH) and paraventricular (PVN) hypothalamic nuclei were studied with anterograde transport of iontophoretically injected Phaseolus vulgaris leuco-agglutinin and the immunocytochemical detection of labeled structures. The LHA was found to give rise to a minor projection in the VMH, whereas the VMH in reverse maintains few connections with the ventromedial part of the tuberal LHA. Tracer deposits in both the LHA and VMH resulted in anterograde terminal labeling in the DMH. The DMH, in turn, donates a small number of projections to the LHA and VMH. The main projection of the DMH is aimed at the parvocellular paraventricular nucleus. Direct outflow pathways from the VMH to the PVN were not found, but lectin injections in the LHA on the other hand gave rise to terminal labeling in both the parvocellular and magnocellular divisions of the PVN. The PVN in turn was found to give only minor reciprocal projections to the LHA, DMH and VMH. These findings indicate that the main stream of connections in the hypothalamus runs from the LHA and VMH to the DMH, and from the DMH to the PVN. The identified circuitry patterns were discussed with respect to the role of the hypothalamus in the control of homeostasis and metabolic regulation, and more specifically in relation to the modulation of the hormone release from the pancreas and adrenal glands.

The projections of the dorsomedial hypothalamic nucleus in the rat.

The dorsomedial hypothalamic nucleus (DMH) output pathways are revealed by using autoradiographic tracing of tritium labeled Leucine and by the recently introduced Phaseolus vulgaris leuco-agglutinin immunocytochemical method. Terminal labeling appears in the dorsal motor nucleus of the vagus, nucleus ambiguus and in the parvocellular reticular formation at the lower medullary level. Mesencephalic labeling is found in the periaqueductal gray at the level of the oculomotor nucleus. In the hypothalamus labeled terminal boutons are identified in the lateral and ventromedial hypothalamic nuclei but also in the parvocellular paraventricular nucleus. Furthermore, the circumventricular organs are found to receive a dense DMH input, particularly the organum vasculosum of the lamina terminalis and the subfornical organ. These findings are discussed in relation to the dorsomedial nucleus involvement in the control of feeding and pancreatic hormone release. It appears that the DMH participates in this control via descending pathways to the preganglionic pancreas innervating neurons but also via a neuroendocrine route. The latter connection is indicated by terminal labeling in the parvocellular paraventricular nucleus in the area that contains the corticotropin-releasing factor positive cells.

Descending pathways from hypothalamus to dorsal motor vagus and ambiguus nuclei in the rat.

The anatomical pathways between the hypothalamus and cell groups of the lower medulla that are involved in the neural control of endocrine pancreas activity were investigated. As part of this control system the descending pathways originating from lateral, dorsomedial and ventromedial hypothalamic nuclei towards the dorsal motor vagus and ambiguus nuclei, were studied by retrograde transport of horseradish peroxidase. Very small injections of the tracer, by means of the iontophoretic delivery method, were placed in the dorsal motor vagus, ambiguus and solitary tract nucleus as well as in the various nuclei of the medullary reticular formation. Subsequent retrograde labeling was studied in the hypothalamus and the brainstem. The appearance of considerable retrograde labeling in mesencephalic periventricular grey and rostral mesencephalic reticular formation indicated a possible role for these structures as intermediates in an indirect hypothalamo-medullary control circuitry. This led us to extend the peroxidase injections to these mesencephalic areas after which the hypothalamus was investigated for retrograde labeling. All data combined indicated the existence of three descending pathways, direct and indirect, between hypothalamus and the parasympathetic motor nuclei of the lower medulla.