The Role of Glia in Addiction: Dopamine as a Modulator of Glial Responses in Addiction.

Addiction is a chronic and potentially deadly disease considered a global health problem. Nevertheless, there is still no ideal treatment for its management. The alterations in the reward system are the most known pathophysiological mechanisms. Dopamine is the pivotal neurotransmitter involved in neuronal drug reward mechanisms and its neuronal mechanisms have been intensely investigated in recent years. However, neuroglial interactions and their relation to drug addiction development and maintenance of drug addiction have been understudied. Many reports have found that most neuroglial cells express dopamine receptors and that dopamine activity may induce neuroimmunomodulatory effects. Furthermore, current research has also shown that pro- and anti-inflammatory molecules modulate dopaminergic neuron activity. Thus, studying the immune mechanisms of dopamine associated with drug abuse is vital in researching new pathophysiological mechanisms and new therapeutic targets for addiction management.

Chemotherapy-induced neuropathic pain characteristics in Mexico's National Cancer Center pain clinic.

Introduction: Chemotherapy (CT) is one of the most commonly used pharmacological approaches in cancer treatment. However, CT induces damage to several tissues causing significant deleterious effects in cancer survivors being chemotherapy-induced neuropathic pain (CINP) among the most commonly reported. CINP is thought to be present in up to 68.1% of the patients within 1 month of receiving CT. Due to the fact that reliable statistic information is scarce in several Latin American countries' diagnosis and treatment of this side-effect may be delayed directly affecting patients. Therefore, the aim of the present study was to determine and present the incidence and features of CINP in patients with cancer attending the Pain Management Clinic at Mexicos' National Institute of Cancerology in Mexico City. Methods: We performed a retrospective, file-based analysis of all the patients treated in the Pain Management Clinic at the National Institute at Cancer in Mexico from January 2016 to January 2017. Results: CINP was found in 30.9% of the patients. The basal VAS was on average 2.5 upon arrival to the Pain Management Unit and 2.4 at the end of treatment (p>0.05). The patients with the highest risk of developing CINP were those treated with paclitaxel Odds ratio 8.3 (p<0.01), followed by platins OR 4 (p<0.01), vincristine OR 1.5 (p=0.01) and thalidomide OR 1.1 (p=0.01). Conclusion: Incidence of CINP was similar to previous reports; however, the number of variables related to this type of pain in our cohort may open a new line of research and highlight the importance of this particular issue to our health system. It is necessary to develop a mechanism to predict the risk of patients to suffer CINP and to search the mechanism to control and reduce the suffering related to the current treatments.

No Difference in Cognitive Dysfunction Among Patients with ANCA-Associated Vasculitis, Rheumatoid Arthritis or Chronic Kidney Disease.

OBJECTIVE: To characterize cognitive function in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in comparison with other chronic conditions, and to investigate its association with disease activity, and other psychological factors. METHODS: Cross-sectional study including patients with AAV, rheumatoid arthritis (RA) (n = 30), and chronic kidney disease (CKD) (n = 29). Patients underwent a standardized neuropsychological battery (NEUROPSI). Sleep quality, fatigue, depression, and anxiety levels were assessed. RESULTS: A total of 60 patients with AAV were included, median age of 54 years, and disease duration of 5.6 years. Prevalence of cognitive dysfunction (CD) in AAV patients was similar to RA and CKD (35%, 40%, and 39.3%, respectively, p = .88). When AAV patients with (n = 21) and without (n = 39) CD were compared, significantly more patients with CD had high disease activity (67% vs. 31%, p = .009). Abnormal performance was more frequent in the executive functions in the three groups (45% AAV, 51.7% RA, and 50% CKD), followed by language (25%, 13.8%, and 25%, respectively). Verbal and visual attentional tests were more frequently impaired in patients from the CKD group (p = .021), and psychomotor functions were more frequently affected in AAV patients (p < .05). Hospital Anxiety and Depression Scale (HADS) total score (especially anxiety) was higher in patients with memory impairment than in those with normal memory function (M = 6.79, SD = 4.53 vs. M = 4.5, SD = 3.6, p < .01). Neither Sleep Quality Index nor fatigue scale scores differed between those cognitively impaired and not impaired. CONCLUSIONS: No statistically significant differences were found in the frequency of CD among the three clinical populations. (JINS, 2019, 25, 595-602).

Ceftriaxone and clavulanic acid induce antiallodynia and anti-inflammatory effects in rats using the carrageenan model.

INTRODUCTION: Ceftriaxone (CFX) and clavulanic acid (CA) are 2 ß-lactam molecules widely used as antibiotics. However, several reports of their antiallodynic properties have been published in recent years. Although this effect has been considered mostly due to a GLT1 overexpression, these molecules have also been proven to induce direct immunomodulation. In this work, we determine the acute analgesic effect of CFX and CA in an inflammatory pain model and assess if their administration may induce anti-inflammatory effects. METHODS: The carrageenan (Carr) test was used as an inflammatory pain model. Both mechanical and thermal responses were analyzed after CFX and CA administration at different times. A plethysmometer was used to determine inflammation. Also, TNF-α and IL-10 serum concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: Both CFX and CA induced a significant thermal antiallodynic effect 3 and 24 h after administration. Furthermore, CA induced a mechanical antiallodynic effect 30, 60, and 90 min after administration. Moreover, a significant anti-inflammatory effect was found for both molecules 24 h after Carr injection. Also, both CA and CFX modulated TNF-α and IL-10 serum concentrations at different times. CONCLUSION: Our results provide evidence that both CFX and CA cause an analgesic effect on a Carr inflammatory pain model and that said analgesic effect differs between each ß-lactam molecule. Furthermore, this effect may be related to an anti-inflammatory effect of both molecules and a direct TNF-α and IL-10 serum concentration modulation.

Patient and physician perspectives on the impact of health-related quality of life in Mexican patients with ANCA-associated vasculitis.

The objective of this study is to describe aspects of health-related quality of life (HRQOL) in Mexican patients with antineutrophil cytoplasmic-associated vasculitis (AAV). Cross-sectional comparison study includes patients with established AAV and a comparison group with rheumatoid arthritis (RA), chronic kidney disease (CKD), and healthy subjects. Variables considered were: socio-demographic data, comorbidities, laboratory, disease activity, damage, and Physician's and Patient's Global Assessment (PhGA and PtGA). The following measurements were done: Pittsburg sleep quality index, Multidimesional Fatigue Inventory (MFI-20), Hospital Anxiety and Depression Scale, Short Form 36 questionnaire (SF-36), and Health Assessment Questionnaire. 60 patients with AAV were included, median age 54 years, and 60% female. Significant differences were found only in the bodily pain domain of the SF-36 (p = 0.01). Aspects of disease relevant for AAV patients were: fatigue and lack of energy; visual abnormalities; neuropathy; renal impairment; arthritis, and sinusitis. Greater total score on MFI-20 (p < 0.001) and worse PtGA (p = 0.01) were associated with worse physical health. Higher PhGA values were associated with worse physical quality of life (p = 0.01). Greater fatigue score (p = 0.002), greater anxiety-depression score (p = 0.005), and worse PtGA (p = 0.01) were associated with worse mental health quality of life. No differences were found in prevalence of sleep impairment, anxiety, depression, or disability between groups. AAV patients experienced more general and physical fatigue (p < 0.0001), and reduced activity (p = 0.01) than healthy subjects, but similar to RA and CKD patients. Vasculitis has negative effects on patients' physical and mental HRQOL.

Histopathologic classification of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis: achievements, limitations, and perspectives.

Clinical and histological factors have been identified as predictors of early and late renal outcome in ANCA-associated vasculitides (AAV). The presence and severity of kidney involvement at diagnosis are associated with poor prognosis in both patient and renal survival. Histologic findings remain the gold standard for diagnosing patients with AAV. In order to quantify the extent of the morphological parameters in the renal biopsies and to identify the histopathological lesions that predict renal outcome, several scoring systems have been proposed to systematically assess kidney biopsies in AAV. Renal pathologists from an international working group proposed in 2010 a new histopathological classification. This scheme comprises four general categories, based on the predominance of the glomerular histological lesions: focal (≥50% normal glomeruli); crescentic (≥50% glomeruli with cellular crescents); mixed (<50% normal, <50% crescentic, <50% globally sclerotic glomeruli), and sclerotic (≥50% globally sclerotic glomeruli). This article reviews the background and the main studies that have validated the histopathologic classification of ANCA-associated glomerulonephritis, the conclusions derived from these studies, and the perspectives for the assessment of renal outcome in AAV.