Lycium barbarum polysaccharide fraction associated with photobiomodulation protects from epithelium thickness and collagen fragmentation in a model of cutaneous photodamage

Lasers in Medical Science - Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The...     

Safety and Efficacy of a Steroid Avoidance Immunosuppression Regimen in Renal Transplant Patients With De Novo or Preformed Donor-Specific Antibodies: A Single-Center Study

Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection.     

The association between social isolation and musculoskeletal health in older community-dwelling adults: findings from the Hertfordshire Cohort Study

Quality of Life Research - Social isolation has been associated with both physical and psychological adverse outcomes and is prevalent in older adults. We investigated the impact of social...     

Specific cerebellar reductions in children with chromosome 22q11.2 deletion syndrome

Children with chromosome 22q11.2 deletion syndrome commonly are found to have morphological brain changes, cognitive impairments, and elevated rates of psychopathology. One of the most commonly and consistently reported brain changes is reduced cerebellar volume. Here, we demonstrate that, in addition to the global cerebellum reductions previously reported, volumetric reductions of the anterior lobule and the vermal region of the neo-cerebellum in the mid-sagittal plane best differentiate children with the deletion from typically developing children. These results suggest that the morphological changes of specific portions of the cerebellum may be an important underlying substrate of cognitive impairments and increased incidence of psychopathology in this group.     

Viral myocarditis: Changing concepts in pathogenesis and implications in diagnosis and treatment

Viral myocarditis is an important potential precursor to idiopathic dilated cardiomyopathy. An understanding of its pathogenesis has evolved with the recent clarification of the role of immune mechanisms, which appears to have both protective and autodestructive effects. In animal models immune modulation has led to paradoxical worsening of the disease, and clinical trials of immunosuppression have not shown any beneficial effects. Through the use of molecular diagnostic techniques, a possible direct role for the virus itself is now increasingly recognized in human disease. This is supported by animal models demonstrating viral cytopathic effects and chronic persistence of virus within the myocardium. A novel contribution from microvascular ischemia has also recently been demonstrated; this may play a particularly important role in the evaluation and treatment of dilated cardiomyopathy. These changing concepts in pathogenesis will have an impact on diagnosis; myocardial biopsy will be used for molecular diagnosis of viral infection, in addition to providing important histological information. Therapy for viral myocarditis will also evolve in parallel to include trials of antiviral agents, targeted immune modulators, and anti-ischemic or vasodilator therapy. With new tools of molecular diagnosis in myocarditis complementing the traditional morphological and immunological assessments, we now have avenues of opportunity to explore in depth the pathogenesis, epidemiology, and prognosis of this challenging disease.     

Phase I clinical study of LL-D49194α1 with retrospective pharmacokinetic investigations in mice and humans

Summary LL-D491941 is a new cytotoxic antibiotic selected for clinical phase I study because of its impressive pre-clinical anti-tumour activity and its low toxicity profile in experimental animals. A total of 15 patients were treated in centres in Glasgow and Amsterdam at doses ranging from 0.25 to 4 mg/m². One minor response was noted in a patient with colonic carcinoma. The study was suspended following the discovery of unexpected cardiotoxicity. As this toxicity was not consistent with the standard (EORTC) European Organisation for Research and Treatment of Cancer toxicology profile, we chose to investigate the pharmacokinetics of LL-D491941 in mice and humans in more detail to try to explain this phenomenon. A major difference in plasma protein binding was discovered between mice and patients, with a suggestion of non-linear kinetics being noted at higher doses in humans. It is likely that these differences in drug handling account for the unexpected and serious toxicity encountered in this trial.     

Effects of continuous exposure to light on behavioral dopaminergic supersensitivity.

BACKGROUND: This study examines the effects of long-term continuous exposure to light on dopaminergic supersensitivity induced by repeated treatment with haloperidol in rats. METHODS: Spontaneous general activity in an open-field (SGA) and stereotyped behavior induced by apomorphine (SB-APO) or amphetamine (SB-AMP) were used as experimental parameters. Rats were allocated to four groups in each experiment: saline-treated animals kept under a 12-hour light/dark cycle (LD) or 24-hour light/light cycle (LL), and 2 mg/kg haloperidol-treated animals kept under the above cycles. Plasma corticosterone concentration was also measured by radioimmunoassay in saline-treated rats kept under a LD or LL cycle. RESULTS: All the behavioral parameters used showed the development of central dopaminergic supersensitivity in rats kept under both cycles. Continuous exposure to light enhanced SGA and SB-AMP in both saline- and haloperidol-treated rats, but did not modify SB-APO. Animals kept under the LL cycle presented an increased plasma corticosterone concentration. CONCLUSIONS: Our results suggest that continuous exposure to light leads to an increase in dopaminergic function in both normal and "supersensitive" rats. This effect seems to be mediated by a presynaptic mechanism possibly involving corticosterone actions.