Influence of growth hormone on the immunosuppressive effect of prednisolone in mice

Growth hormone can be used to counteract some catabolic effects of long-term administration of glucocorticoids, such as impairment of growth in children and osteoporosis. However, owing to its immunostimulatory properties the hormone may counteract the effect of glucocorticoids on the immune system. To investigate this question we administered different doses of hGH (4, 8, 40 IU/kg) to C57/Bl/6J mice treated for two days with prednisolone, and evaluated thymus and spleen parameters and natural killer activity. Growth hormone at the dose of 4 and 8 IU/kg reversed prednisolone-induced reduction of spleen and thymus weight and cellularity, whereas the highest dose showed to be immunosuppressive in itself. Two days after treatment withdrawal, a recovery of spleen parameters was evident, whereas the thymus was still suppressed by preceding prednisolone or hGH (40 IU/kg) treatments. The pattern of natural killer activity displayed by the splenocytes resembled that present under treatment. In a second experiment prednisolone, administered for 10 days, drastically reduced the number of viable spleen and thymus cells as well as the relative spleen and thymus weights, an effect reversed by concomitant administration of hGH (0.8, 4, 8 IU/kg). Natural killer activity, which was significantly depressed by prednisolone, was restored by the intermediate GH dose only. The 8 IU/kg GH dose was immunosuppressive in itself.     

Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients

Introduction

Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects.

Methods

Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios.

Results

365 patients were enrolled, and 289 patients with follow-up (age 67.7 ± 7.3 years, 237 males, mean follow-up 40 ± 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project.

Conclusions

Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.     

Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1...     

Efficacy of TTFCA in reducing the ratio between lymphatic and plasma protein concentration in lymphatic and postphlebitic edema]

In subjects with lymphatic problems and postphlebitic edema there is a significant difference in the ratio between lymphatic and plasma concentration of protein (CL/CP) in the foot. Two groups of patients were studied (one group with lymphedema and the other with postphlebitic limbs) in order to assess the CL/CP ratio before and after TTCFA treatment (Centellase). The study confirmed the efficacy of treatment in achieving a significant reduction of CL/CP and distal edema.     

Low dose of ethinyl estradiol can reverse the antiestrogenic effects of clomiphene citrate on endometrium

Fifty healthy, voluntary patients aged between 20 and 30 years with regular menstruation and plasmatic progesterone level >10 ng/ml at the midluteal phase have been enrolled in this study. They were randomly treated with clomiphene citrate (CC; group A) or CC + ethinyl estradiol (0.05 mg group B, or 0.02 mg group C). We estimated the difference in uterine artery pulsatily index, endometrial thickness and histological dating and morphometric analysis of endometrium. No significant differences in Pulsatility Index values and in the number of preovulatory follicles were noted. The difference between endometrial thickness, histological dating and morphometric analysis of the endometrium were statistically different between groups B and C vs. A. Our study shows that CC has a deleterious effect on endometrium maturity and that adding ethinyl-E(2) produces a favorable endometrial response even with very low doses.     

Monoclonal antibody against human growth hormone receptor

GHR shows a high degree of homology with the prolactin receptor and with the other receptors that belong to the hemopoietic receptor superfamily. This paper describes a monoclonal antibody (MAb) (2B4B6) specific for both the extracellular domain of human GHR and human growth hormone (GH) binding protein. Mice were immunized against a seven-aminoacid peptide sequence screened by FASTA (sequence similarity search served by Genome-Net) from the European Bioinformatics Institute to exclude the existence of human membrane proteins with significant sequence homology. MAbs were screened against the peptide sequence and 2B4B6 was selected for its capability to recognize the full-length hGHBP. As evaluated by both enzyme-linked immunoadsorbent assay (ELISA) and FACS analysis, this MAb seems to recognize and bind to a hGHR positive cell line, IM-9, as well as a murine cell line, BaF3 (8/6), transfected with a chimeric construct, hGHR/hG-CSFR and expressing hGHR on the cell membrane. Studies investigating the biological effects of this MAb showed that anti-hGHR mediated inhibition of cell proliferation was not due to competition with GH binding but rather to prevention of receptor dimerization. Because of its specificity, this MAb may be usefully applied in situations in which GHR and receptors with a high degree of homology, such as PRLR (prolactin receptor), are expressed simultaneously, as occurs in the immune system.