Cyclooxygenase-2/PGE2 pathway facilitates pentylenetetrazol-induced seizures

Cyclooxygenases (COXs) are rate-limiting enzymes in the metabolic pathways in which arachidonic acid is converted to prostaglandins. COX-2 is the isoform induced at injury/inflammation sites and expressed constitutively in a few tissues, such as the central nervous system, and plays a role in neurodegenerative diseases associated with increased excitatory activity. However, the role of COX-2 and its main product, prostaglandin E(2) (PGE(2)), in the convulsive states is not fully established. In this study we showed that the selective COX-2 inhibitor, celecoxib (at the dose of 2mg/kg, but not at the doses of 0.2 or 20mg/kg, p.o.), protects against the seizures induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.). The role of PGE(2) in the convulsions induced by PTZ was further investigated by administering anti-PGE(2) antibodies (4 microg/2 microl, i.c.v.), and assessing electroencephalographic changes induced by PTZ (PTZ, 60 mg/kg, i.p.). Anti-PGE(2) antibodies attenuated PTZ-induced seizures in rats. In addition, combining PGE(2) (100 ng/2 microl, i.c.v.) with a subconvulsant dose of PTZ (20mg/kg, i.p.) caused seizures, further supporting a role for this prostaglandin in the convulsions induced by PTZ. Finally, we showed that the anticonvulsant action of celecoxib (2mg/kg, p.o.) was reversed by the intracerebroventricular administration of PGE(2) (10 ng/2 microl, i.c.v.). These data constitute strong converging pharmacological evidence supporting a facilitatory role for the COX-2/PGE(2) pathway in the seizures induced by PTZ. However, whether selective COX-2 inhibitors are safer anti-inflammatory drugs for epileptic patients than nonspecific inhibitors remains to be determined.     

Special features of SARS-CoV-2 in daily practice

The severe acute respiratory syndrome-coronavirus-2 (commonly known as SARS-CoV-2) is a novel coronavirus (designated as 2019-nCoV), which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan, China in December 2019. Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines, based on scientific evidence and experts’ opinions with clinical experience, are constantly being updated. On January 30, 2020, the World Health Organization declared the SARS-CoV-2 outbreak as a Public Health Emergency of International Concern. The total lack of immune protection brought about a severe spread of the contagion all over the world. For this reason, diagnostic tools, patient management and therapeutic approaches have been tested along the way, in the desperate race to break free from the widespread infection and its fatal respiratory complications. Current medical knowledge and research on severe and critical patients’ management and experimental treatments are still evolving, but several protocols on minimizing risk of infection among the general population, patients and healthcare workers have been approved and diffused by International Health Authorities.     

Deuterium nuclear magnetic resonance for evaluating the metabolic status of livers subjected to warm ischemia.

BACKGROUND: The development of reliable methods for assessing the viability of currently available livers is expected to increase the number of successful transplantations. METHODS: 2 H nuclear magnetic resonance (NMR) was used to search for metabolic markers of ischemia in explanted rat livers. Deuterium oxide (2 H2O) was used as a source of 2 H. A total of 10-80% v/v 2 H2O was added to homogenates obtained from a liver biopsy and the formation of 2 H-labeled metabolites was monitored. RESULTS: Some well-resolved 2 H resonances were found in the homogenates from biopsies of warm ischemic liver. Two of these were identified as [3-2 H] lactate and [2-2 H] lactate, and a linear relationship was found between the ratio of [[2-2 H] lactate] to [[3-2 H] lactate] and the warm ischemia time. The deuterium incorporation into lactate was explained on the basis of the metabolic events occurring under hypoxic conditions. CONCLUSIONS: The experimental results support the application of 2 H NMR for a reliable evaluation of the metabolic status of a liver harvested from non-heart-beating donors.     

A Comparative Assessment of Quality of Life in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation Through an Outpatient and Inpatient Model

Outpatient autologous stem cell transplantation (ASCT) has proven to be feasible in terms of physical morbidity and mortality outcomes, but little data exist on the impact of this procedure on quality of life (QoL). The purpose of this prospective, observational, longitudinal cohort study was to compare the effects of inpatient (n?=?76) and outpatient (n?=?64) modes of care on QoL in patients with multiple myeloma who underwent ASCT. Patients were treated according to their preference for the inpatient or outpatient model. QoL was assessed using the Functional Assessment of Cancer Therapy–Bone Marrow Transplantation (FACT-BMT) at baseline (7 days before ASCT; T1) and at days +7 (T2) and +30 (T3) after ASCT. Overall, inpatients achieved higher mean values at each time point (86.05?±?15.54 at T1, 89.23?±?19.19 at T2, and 87.96?±?13.6 at T3) compared with outpatients (85.62?±?14.51 at T1, 87.42?±?23.41 at T2, and 83.98?±?20.2 at T3), although the differences did not reach statistical significance. Inpatients showed higher mean scores than outpatients in physical well-being (7.67?±?5.7, 15.44?±?6.34, and 12.96?±?6.03, respectively, versus 5.89?±?4.33, 13.92?±?7.05, and 8.84?±?6.33, respectively; P?<?.05). Mean scores on social/family well-being were significantly higher in the outpatient group compared with the inpatient group (22.93?±?13.29, 21.14?±?5.31, and 21.64?±?4.58, respectively, versus 20.59?±?3.79, 19.52?±?5.12, and 20.01?±?3.97, respectively; P?=?.003). There were no significant between-group differences with respect to functional well-being and emotional status. Among adults at a single institution undergoing ASCT for MM, the use of outpatient care compared with standard transplantation care did not result in improved QoL during transplantation. Further research is needed for replication and to assess longer-term outcomes and implications.     

High values of alpha (CXCL10) and beta (CCL2) circulating chemokines in patients with psoriatic arthritis, in presence or absence of autoimmune thyroiditis

The possible role of circulating alpha and beta chemokines in psoriatic arthritis is not extensively studied. The aim of the study is to evaluate serum levels of CXCL10, CXCL9 (alpha) and CCL2 (beta) chemokines in a large series of psoriatic arthritis patients, with or without autoimmune thyroid (AT) disorders, and to relate chemokines levels to the clinical phenotype of these patients. Serum levels of CXCL10 and CCL2 were measured in 37 patients with psoriatic arthritis without AT (PsA) and 28 with AT (PsA+AT), and in gender- and age-matched (1:1) controls without (control 1) or with AT (control 2). Serum CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.001) and in PsA than control 1 or 2 (p < 0.0001). PsA+AT patients have CXCL10 higher than controls 1 and 2 (p < 0.0001, for both) and than PsA (p < 0.001). By defining a high CXCL10 level as a value at least 2 SD above the mean value of the control group (>192 pg/ml), 5% of control 1, 19% of control 2, 42% of PsA and 63% of PsA+AT, had high CXCL10 (p < 0.0001; chi(2)). Serum CCL2 levels were similar in controls 1 and 2. PsA or PsA+AT patients have serum CCL2 levels significantly (p < 0.01, for both) higher than controls 1 and 2. Serum CXCL9 was not significantly different in the study groups. In conclusion, our study demonstrates higher serum levels of CXCL10 and CCL2 chemokines in patients with PsA than in controls. Serum CXCL10 (alpha chemokine) levels in psoriatic arthritis patients are significantly higher in presence of AT.     

Histological markers of humoral rejection in renal transplant patients

Diagnosis of "suspicious humoral rejection" can be formulated in the presence of peritubular capillary (PTC) C4d deposition and one of the following tissue changes: (1) acute tubular necrosis, (2) glomerulitis or presence of polymophonuclear leukocytes or monocytes in PTC, or (3) arteritis. From January 2004 to October 2006, we performed immunohistochemical staining with anti-C4d antibody on 54 renal biopsies from 39 renal transplant patients. In 25 biopsies we observed diffuse (n = 13) or focal (n = 12) C4d deposition. Based on C4d-positivity, patients were divided into three groups: group 1 included 19 C4d-negative patients; group 2, 10 patients with diffuse C4d-positivity; and group 3, 10 patients with focal C4d-positivity. Panel-reaction antibody-positive tests were associated with diffuse C4d-positivity: 50% of group 2 patients showed a positive test, while no group 1 or 3 patients had a positive test (P < .001). Glomerulitis was observed in six biopsies and associated with diffuse C4d staining. Graft loss occurred in 3/10 group 2 patients (30%); 2/19 group 1 patients (10.5%), and 1/10 group 3 patients (10%). Viral infections were experienced in the year of the biopsy by 50% of group 1 patients 80% of group 2 patients, and 100% of group 3 patients (P < .025), indicating a significantly greater number of infections among patients with C4d-positive biopsies. In eight cases, anti-thymocyte globulin was administered less than 21 days before the biopsy: four had diffuse and four had focal C4d positivity.