Receptor changes in brain tissue of rats treated as neonates with capsaicin

Capsaicin, the hot chemical in chillies, administered to neonatal rats, causes destruction of polymodal nociceptive primary afferent neurons by acting on TRPV1 receptors causing intrinsic somatosensory deprivation. Although the effects of neonatal capsaicin treatment in the periphery have been extensively investigated, less is known about the brain networks to which the capsaicin sensory neurons are relayed. In the present study the effect of neonatal capsaicin treatment on brain receptors that have been shown to interact with TRPV1 was examined. Wistar rats were treated on neonatal day 2 with capsaicin and at 15–16 weeks of age, brains were processed to measure levels of muscarinic M₁/M₂ and M₂/M₄, serotonin 5HT₂A, cannabinoid CB₁, dopamine D₁, D₂ receptors and dopamine transporter. Overall increases in levels of muscarinic M₁/M₄ (F = 8.219, df = 1, p = 0.005), muscarinic M₂/M₄ (F = 99.759, df = 1, p < 0.0001), serotonin 5HT₂A (F = 28.892, df = 1, p < 0.0001), dopamine D₁ (F = 8.726, df = 1, p = 0.008) and cannabinoid CB₁ (F = 25.084, df = 1, p < 0.0001) receptors were found in the brains of capsaicin-treated rats, although significant regional changes occurred only in muscarinic M₂/M₄ and serotonin 5HT₂A receptors. The results of the present study suggest that neonatal intrinsic somatosensory deprivation may have a significant impact on substrates at the central nervous system that manifest as changes in central cholinergic, monaminergic and cannabinoid systems in the adult animal

Effect of subchronic administration of tachykinin antagonists on response of guinea-pigs to mild and severe stress

The effects of subchronic subcutaneous treatment with tachykinin receptor antagonists over nine days on the repeated mild stress response induced by daily subcutaneous injections and on the severe acute stress induced by morphine withdrawal were investigated in guinea-pigs. The NK₁ receptor antagonist, L733,060, 0.25 mg/kg, significantly increased locomotor activity of guinea-pigs compared with animals subjected to repeated injection of the inactive enantiomer, but inhibited Fos-like immunoreactivity (Fos-LI) in the hypothalamus. In animals subjected to the acute severe stress of naltrexone-induced morphine withdrawal, treatment with the NK₁ antagonist, L733,060, produced reductions in Fos-LI in the spinal dorsal horn, whereas those treated with the NK₃ antagonist, SSR146,977, 0.3 mg/kg, had reduced Fos-LI in the dorsal horn, adrenal medulla, nucleus accumbens, ventral tegmental area and periaqueductal grey. Those animals treated with both NK₁ and NK₃ antagonists also had reduced Fos-LI in the amygdala and paraventricular nucleus of the thalamus. It was concluded that the NK₁ antagonist reduced the hypothalamic response to mild stress but the NK₃ antagonist was more effective in reducing the severe stress response to morphine withdrawal. Furthermore, combination of NK₁ and NK₃ antagonists was more effective than either antagonist in reducing the Fos-LI response to morphine withdrawal

Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy : a systematic review using individual patient data

PURPOSE: We conducted a systematic review and individual patient data (IPD) meta-analysis to examine the utility of cystatin C for evaluation of glomerular function in children with cancer. METHODS: Eligible studies evaluated the accuracy of cystatin C for detecting poor renal function in children undergoing chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies shared IPD. We calculated the correlation between log cystatin C and GFR stratified by study and measure of cystatin C. We dichotomized the reference standard at GFR 80 ml/min/1.73m2 and stratified cystatin C at 1 mg/l, to calculate sensitivity and specificity in each study and according to age group (0-4, 5-12, and ≥ 13 years). In sensitivity analyses, we investigated different GFR and cystatin C cut points. We used logistic regression to estimate the association of impaired renal function with log cystatin C and quantified diagnostic accuracy using the area under the ROC curve (AUC). RESULTS: Six studies, which used different test and reference standard thresholds, suggested that cystatin C has the potential to monitor renal function in children undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children) showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%), although use of a GFR cut point of < 60 ml/min/1.73m2 (data only available from two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic accuracy appeared to decrease with age. CONCLUSIONS: Cystatin C has better diagnostic accuracy than creatinine as a test for glomerular dysfunction in young people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for it to replace current reference standards for predicting clinically relevant impairments that may alter dosing of important nephrotoxic agents

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

1. Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. 2. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg(−1) subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. 3. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. 4. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. 5. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. 6. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia

Energy levels of Z = 11−21 nuclei (IV)

Compilation of experimentally determined properties of energy levels of Z = 11−21 nuclei with special emphasis on nuclear spectroscopy