Comment on “A meta-analysis of fracture risk and bone mineral density in patients with systemic sclerosis”

Clinical Rheumatology -     

Does sublingual microscopy correlate with nailfold videocapillaroscopy in systemic sclerosis?

Clinical Rheumatology - In this study, we examine sublingual videomicroscopy and nailfold videocapillaroscopy (NVC) features in systemic sclerosis (SSc) patients presenting for routine care....     

Study of the compatibility of poly(ethylene oxide) with polyitaconates

This paper reports on the compatibility of poly(ethylene oxide) (PEO) towards poly(monobenzyl itaconate) (PMBzl) and poly(dibenzyl itaconate) (PDBzl) in the bulk by analyzing the melting point depression of the crystalline component and the influence of the amorphous material on the crystallization kinetics of the former. The experimental data obtained suggest compatibility for the PEO/PMBzl blend and incompatibility for the PEO/PDBzl system. This behaviour is explained by specific interactions (hydrogen bonds) between the chains, and is compared with that of other polymers with similar chemical structure.     

Gene frequencies of platelet‐specific antigens in Croatian population

The human platelet antigens (HPA) are genetically defined polymorphisms expressed on platelet membrane glycoproteins. As platelet antigens are very important in several clinical situations and in population genetics, we used the polymerase chain reaction with sequence‐specific primers (PCR‐SSP) to investigate HPA‐1, ‐2, ‐3 and ‐5 allele frequencies in the Croatian population. The HPA frequencies obtained in 219 Croatians were: 1a–0·854, 1b–0·146, 2a–0·890, 2b–0·110, 3a–0·575, 3b–0·425, 5a–0·895 and 5b–0·105. These data are similar to the frequencies reported in most European studies with some significant differences in HPA‐2 when compared with the Dutch and German population, in HPA‐3 when compared with the Swiss population and in HPA‐5 when compared with the Finnish population. The three most common condensed HPA genotypes in the Croatian population were: HPA‐1a/a, ‐2a/a, ‐3a/b, ‐5‐a/a (0·283), HPA‐1a/a, ‐2a/a, ‐3a/a, ‐5‐a/a (0·137) and HPA‐1a/b, ‐2a/a, ‐3a/b, ‐5‐a/a (0·087). Data obtained in this study can be used for better understanding and treatment of immune‐mediated platelet disorders in our population.     

Analysis of autoimmune bone marrow by antibody-phage display: somatic mutations and third complementarity-determining region arginines in anti-DNA gamma and kappa V genes

OBJECTIVE: To examine anti-double-stranded DNA (anti-dsDNA) IgG autoantibodies from the bone marrow of individuals with systemic lupus erythematosus (SLE). METHODS: A library of single-chain variable fragments (scFv) was constructed from SLE bone marrow complementary DNA of gamma, kappa, and lambda isotype by cloning into the pHENIX phagemid vector. The library was screened with dsDNA in solution, and 2 anti-DNA phage, DNA1 and DNA4, were isolated and their Ig V genes sequenced. Soluble scFv corresponding to DNA1 and DNA4, and their heavy (H)- and light (L)-chain recombinants, were prepared, purified, and analyzed for binding to DNA by enzyme-linked immunosorbent assay. RESULTS: DNA1 and DNA4 used different Ig H-chain (3-30 and 5-51, respectively) and L-chain (DPK15 and DPK22, respectively) V genes. The ratios of replacement mutations to silent mutations in DNA1 and DNA4 suggest that their V genes were selected for improved antigen binding in vivo. The recombinant between DNA4VH and DNA1VL showed the highest relative affinity for both single-stranded DNA and dsDNA. These 2 Ig subunits contained third complementarity-determining region arginines and had acquired the majority of replacement mutations. CONCLUSION: Anti-dsDNA IgG autoantibodies from the bone marrow of SLE patients exploit diverse V genes and cationic V-D-J and V-J junctions for DNA binding, and accumulate replacement mutations that enhance binding.     

Liver disease in the era of COVID-19: Is the worst yet to come?

The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health systems. Drastic lifestyle changes, social isolation and distancing, and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages, drugs and unhealthy diets. The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease, viral hepatitis, acute alcoholic hepatitis, liver cirrhosis decompensation and ultimately liver-related mortality. The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease (CLD) and has prevented prompt hepatocellular carcinoma detection and treatment. A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation. The indirect, unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined. Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated. Several questions regarding the impact of the COVID-19 pandemic on liver disease remain. The most important question for general CLD patients is: How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients? This article reviews the influence of COVID-19 on patients with liver disease during the pandemic, with particular emphasis on the disease course associated with pandemic resolution.     

Stable Gastric Pentadecapeptide BPC 157 in Trials for Inflammatory Bowel Disease (PL-10, PLD-116, PL14736, Pliva, Croatia) Heals Ileoileal Anastomosis in the Rat

Purpose Gastric pentadecapeptide BPC 157 (BPC 157), which has been shown to be safe in clinical trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia), may be able to cure intestinal anastomosis dehiscence. This antiulcer peptide shows no toxicity, is limit test negative, and a lethal dose is not achieved. It is stable in human gastric juice. In comparison with other standard treatments it is more effective for ulcers and various wounds, and can be used without a carrier needed for other peptides, both locally and systemically (i.e., perorally, parenterally). We studied the effectiveness of BPC 157 for ileoileal anastomosis healing in rats. Methods We assessed ileoileal anastomosis dehiscence macroscopically, histologically, and biomechanically (volume [ml] infused through a syringe-perfusion pump system (1 ml/10 s), and pressure [mmHg] to leak induction [catheter connected to a chamber and a monitor, at 10 cm proximal to anastomosis]), at 1, 2, 3, 4, 5, 6, 7, and 14 days. BPC 157 (10 μg, 10 ng, 10 pg/kg i.p. (or saline [5 ml/kg]) was first administered after surgery, while it was last given 24 h before either assessment or sacrifice. Results Throughout the experiment, both higher doses of BPC 157 were shown to improve all parameters of anastomotic wound healing. The formation of adhesions remained slight, the blood vessels were filled with blood, and a mild intestinal passage obstruction was only temporarily observed. Anastomosis without leakage induces markedly higher volume and pressure values, with a continuous increase toward healthy values. From day 1, edema was markedly attenuated and the number of granulocytes decreased, while from days 4 or 5 necrosis decreased and granulation tissue, reticulin, and collagen formation substantially increased, thus resulting in increased epithelization. Conclusion This study showed BPC 157 to have a beneficial effect on ileoileal anastomosis healing in the rat.     

Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer

The effects of fullerenol C₆₀(OH)₂₄ (Frl) at doses of 25, 50, and 100 mg/kg/week (for a time-span of 3 weeks) on heart and liver tissue after doxorubicin (Dox)-induced toxicity in rats with colorectal cancer were investigated. In the present study, we used an in vivo Wistar male rat model to explore whether Frl could protect against Dox-induced (1.5 mg/kg/week for 3 weeks) chronic cardio- and hepato- toxicity and compared the effect with a well-known antioxidant, vitamin C (100 mg/kg/week for 3 weeks). According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.     

Benzodiazepine use among the elderly in the community.

Benzodiazepines are the most commonly prescribed psychotropic drug in the elderly. Benzodiazepines with a long duration of action can produce marked sedation and psychomotor impairment in older people, and are associated with an increased risk of hip fracture and of motor vehicle crash. One thousand seven hundred and one individuals of 65 years and over, identified from General Practitioner lists, were interviewed using the Geriatric Mental State-AGECAT package and current psychotropic drug use was recorded. Benzodiazepines were classified as having a short or long elimination half-life. Two hundred and ninety-five (17.3%) individuals were taking a benzodiazepine, with use in females being twice that in males. Of the 295, 152 (51.5%) were taking a long acting benzodiazepine and the use of long acting anxiolytic type benzodiazepines was particularly common. Fifty-two (17.6%) benzodiazepine users were taking one or more other psychotropic drugs. A benzodiazepine was used by eight of 18 (44.4%) subjects with an anxiety disorder, 62 of 180 (34.4%) individuals with depression, and seven of 71 (9.9%) people with dementia. Four-fifths of older people on a psychotropic drug were taking a benzodiazepine, highlighting the importance of this class of drug in the elderly population. The choice of a benzodiazepine with a long duration of action, which have been shown to be associated with serious adverse events in the elderly in over one half of benzodiazepine users, is of concern. The potential for adverse effects was further accentuated by polypharmacy practices. The choice of benzodiazepine for an older person has important consequences and should be addressed in greater detail with primary care.