Granulocyte macrophage colony-stimulating factor as an adjuvant for hepatitis B vaccination: a meta-analysis

The efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance the immune response to hepatitis B virus vaccine has been object of several reports. We searched for randomized controlled clinical trials comparing GM-CSF given concomitantly to hepatitis B virus vaccine to vaccine given alone or with placebo. Data on rates of seroconversion (anti-HBs titers >10 IU/ml) from 13 studies (734 subjects) produced combined estimates that favored GM-CSF as compared to controls: rate ratio after a single immunization was 1.54 [95% confidence interval (CI), 1.04-2.27] and 1.20 (95% CI, 1.02-1.42) at the end of the vaccination cycle. Using a logistic approach a significant dose/response effect of GM-CSF was seen. Moreover, in renal failure patients who have responded to the vaccine, GM-CSF increased anti-HBs titers. Our findings suggest that GM-CSF induced a significant effect in terms of response rate and achievement of an earlier seroconversion to the vaccine in the overall populations examined, in renal failure patients and in healthy individuals.     

Comparative growth and toxin profile of cultured Ostreopsis ovata from the Tyrrhenian and Adriatic Seas

Massive blooms of the benthic dinoflagellate Ostreopsis ovata Fukuyo have recently occurred along the whole Italian coastlines, both Tyrrhenian and Adriatic, resulting sometimes in benthonic biocenosis sufferings and, occasionally, in human health problems. In this work, two strains of O. ovata collected in 2006 along the Adriatic and Tyrrhenian coastlines and grown in culture were studied to characterize their growth and toxin profile. The two strains showed different cell volumes, the Adriatic strain being nearly twice bigger than the Tyrrhenian, but they had similar slow growth rates. Liquid chromatography-mass spectrometry (LC-MS) analyses indicated that both strains produce putative palytoxin (pPLTX) and ovatoxin-a (OVTX-a), a palytoxin-like compound presenting 2 oxygen atoms less than palytoxin.Toxin content was determined at the end of the stationary and exponential growth phases and reached the highest value in the Adriatic strain at the end of the stationary phase, with concentrations of 353.3 μg l^?1 for OVTX-a and 30.4 μg l^?1 for pPLTX. Toxin released in the growth medium was also measured and resulted to be the highest at the end of the stationary phase, suggesting that a long lasting bloom could enhance the toxin content in the water and cause toxic effects in people inhaling the aerosol.     

Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, because ICIs block coinhibitory molecules on T cells and other immune cells, unleashing them to mediate tumor cell killing, they also can disrupt the maintenance of immunological tolerance to self‐antigens. Compared with chemotherapy, ICIs have a different toxicity profile, especially the occurrence of autoimmune‐like manifestations against multiple organ systems, including endocrine glands, commonly referred to as immune‐related adverse events. The aim of this review was to provide practical recommendations regarding the proper assessment and clinical management related to the new onset of endocrinopathies after the use of ICIs in patients with cancer. Cancer 2018;124:1111‐21. © 2018 American Cancer Society.     

Alternative strategies for carcinogenicity assessment: an efficient and simplified approach based on in vitro mutagenicity and cell transformation assays

The need for tools able to predict chemical carcinogens in less time and at a lower cost in terms of animal lives and money is still a research priority, even after several decades of effort in that direction. Now, new regulatory requirements (e.g. the Registration, Evaluation, Authorisation and Restriction of Chemical substances recently implemented in Europe) have even increased the pressure to develop new tools in this field. Drawbacks of the present testing strategies have come to light again recently especially in view of new requirements in worldwide regulations. Among these are (i) the lack of assays able to identify non-genotoxic carcinogens, (ii) the exaggerated rate of misleading (false) positive results of the in vitro mammalian cell-based short-term mutagenicity tests and (iii) the extremely low sensitivity of in vivo short-term mutagenicity tests. Within this perspective, we analyse the contribution of cell transformation assays (CTAs), and we show that they are a valid complement to tools able to detect DNA-reactive carcinogens. We also show that a tiered strategy, with inexpensive and fast tests in Tier 1 (e.g. the Ames test or structural alerts) and the Syrian hamster embryo CTA in Tier 2, is able to identify up to 90% of carcinogens.     

Quantitative development of the subcommissural organ in hypothyroid mice

The postnatal development of the global volume of the subcommissural organ (SCO) and of the karyometric changes of the ependymocytes in the SCO and the adjacent ventricle is studied in male albino mice aged from 25 to 160 days, and in a hypothyroid group treated with propylthiouracil with and without interruption of the treatment at 35 days. Hypothyroidism produces a decrease of the global volume of the SCO and of the nuclear size of the ependymocytes in the SCO and the adjacent ventricle.     

Morphometric changes in alcoholic mice of neurons of areas 6 and 17 and ependyma of the subcommissural organ

We have performed a karyometric study of the postnatal development of the subcommissural organ (SOC), the subjacent thalamic ependyma, and the pyramidal neurons of layer V of the motor and visual cortical areas, in alcoholic male albino mice, aged 25-100 days. Ethyl alcohol was added to the drinking water at a concentration of 20%, from birth until the day of sacrifice. Our results show that alcoholism affects the SOC ependyma and the motor cortex, and, apparently, does not affect the ventricular thalamic ependyma and the visual cortex. We suggest a neuroendocrine mechanism to explain the SOC answer, and a functional deprivation to explain the changes in the motor cortex.     

Mesangial cell proliferation in long-term streptozotocin-induced diabetes mellitus in the rat and the renoprotective activity of heparin.

At present, it is not clear whether mesangial proliferation underlies mesangial expansion in diabetic nephropathy. To address this issue and the relationship between heparin's renoprotective and antimitogenic activities, we studied three streptozotocin-induced diabetic rat groups 5 and 12 months after diabetes induction: two groups were administered a modified heparin, each with a different protocol, and two healthy rat groups, one of which was treated with the same heparin, served as controls. Untreated diabetic animals developed clear evidence of nephropathy, namely expansion of the glomerular extracellular matrix, as expressed by glomerular basement membrane thickening, and increased mesangial deposition of type IV collagen. These alterations were prevented/cured by heparin treatment. Kidney sections were processed immunohistochemically for proliferating cell nuclear antigen and smooth muscle alpha-actin which is expressed only by proliferating mesangial cells. The number of proliferating cell nuclear antigen positive nuclei and alpha-actin-positive cells per glomerulus did not differ between groups at both 5 and 12 months. In conclusion, there is no evidence that mesangial proliferation is increased in late experimental diabetic nephropathy, and heparin seems to be renoprotective through mechanisms other than antiproliferation.     

Obesity Surgery in the Philippines: Experience in a Private Tertiary Care Hospital for Years 2002 to 2004

Background Information on experience in bariatric surgery in the Asia-Pacific region is minimal: hence the need for more reports from this area. Methods The procedures of bariatric surgery and outcome as part of a weight management program in a tertiary care private hospital in the Philippines is reported from years 2002 to 2004. 50 patients were included, of which 60% underwent laparoscopic adjustable gastric banding (LAGB) and 40% Roux-en- Y gastric bypass (RYGBP). Results There were more females than males (64% vs 36%) with the mean age 38 ± 13.1 years. Initial mean BMI was 46.2 kg/m2, which decreased to 27.0 kg/m² in 1 year. Initial mean weight was 126.7 ± 25.4 kg, of which the 1 year weight loss was 32.3 kg for the morbidly obese and 58.0 kg for the super obese. %EWL at 1 year was 30.2%. There was greater weight loss with RYGBP compared to LAGB at 1 year (43.5 kg vs 30.2 kg). There was no mortality, and early complications were: wound infection (2/50 or 4%), and 1/50 or 2% each for pneumonia, dehydration, gastritis, and leakage. Late complications were: band slippage (2/20 or 10%), stomal stenosis (1/20 or 5%), and ventral hernia (1/5 or 20%). Conclusion Bariatric surgery is safe with a low complication rate and the outcome was similar to the reported data from Asia and the western world.