Sjögren's syndrome with myalgia is associated with subnormal secretion of cytokines by peripheral blood mononuclear cells

OBJECTIVE: To measure in vitro cytokine release from peripheral blood mononuclear cells (PBMC) and serum cytokines in patients with primary Sj?gren's syndrome (SS) with and without myalgia, compared to patients with rheumatoid arthritis (RA) and healthy controls. METHODS: Sixteen women with SS (8 with myalgia, 8 without pain), 15 women with RA, and 14 healthy women were studied. PBMC were isolated and cultured. Secretion of interleukin 1 beta (IL-1 beta), IL-6, IL-10, and tumor necrosis factor-alpha (TNF-alpha) was measured in cell supernatants with or without stimulation with phytohemagglutinin, tetanus toxoid, or purified protein derivative (PPD). Enzyme-linked immunospot was used to enumerate interferon-gamma (IFN-gamma) and IL-4-secreting cells. Serum concentrations of IL-8 and IL-18 were analyzed by ELISA. RESULTS: PPD-stimulated PBMC from SS patients responded with less production of IL-10, TNF-alpha, and IFN-gamma compared to controls. Patients with SS and pain were hyporesponsive also with respect to IL-1 beta and IL-6. The generally subnormal cytokine release was statistically significant in myalgic patients with SS compared to healthy controls. Serum IL-18 was increased in both SS groups as well as in patients with RA, and the highest levels were found in myalgic patients with SS. Serum IL-8 was increased in RA but not in SS. CONCLUSION: Patients with SS, especially those with myalgia, had diminished PBMC cytokine release and increased serum IL-18. This finding suggests that impaired cytokine regulation may have pathogenetic importance for myalgia in SS.     

Genotyping and characterization of two polymorphic microsatellite markers located within introns 29 and 30 of the human thyroglobulin gene.

The purpose of the present work was to characterize two new polymorphic microsatellite markers in the thyroglobulin gene. TGrI29 and TGrI30 repeats are located within introns 29 and 30, respectively. Genetic studies were carried out by using polymerase chain reaction (PCR) followed by denaturing polyacrilamide gel electrophoresis. TGrI29 exhibited clearly 4 distinguishable alleles ranging from 197 to 203 base pair (bp) in length and TGrI30 showed 8 alleles ranging from 502 to 542 bp. We characterized the two markers by determinating allele frequencies and measures of variation. The heterozygosities (HET) observed of TGrI29 and TGrI30 were 0.859 and 0.522, respectively. The polymorphism information contents (PIC) were 0.471 and 0.434, respectively. No significant differences from Hardy-Weinberg values were found for these two systems. The PCR products of each allele were cloned using the pGEM-T Easy vector and directly sequenced by Taq polymerase-based chain terminator method. Sequencing analysis indicated that both loci are complex repeats, TGrI29 containing two types of variable motifs (tc)n and (tg)n, and TGrI30 a tetra-nucleotide tandem units (atcc)n. In two TGrI29 alleles and one TGrI30 allele were found two different subtypes in each one, with the same molecular weights but different distribution of the tandem repeats. In conclusion, both microsatellites analyzed are highly informative polymorphic markers and can be used in linkage studies in families with congenital hypothyroidism or autoimmunity thyroid diseases.     

Alcohol use in times of the COVID 19: Implications for monitoring and policy

Based on a literature search undertaken to determine the impacts of past public health crises, and a systematic review of the effects of past economic crises on alcohol consumption, two main scenarios—with opposite predictions regarding the impact of the current COVID‐19 pandemic on the level and patterns of alcohol consumption—are introduced. The first scenario predicts an increase in consumption for some populations, particularly men, due to distress experienced as a result of the pandemic. A second scenario predicts the opposite outcome, a lowered level of consumption, based on the decreased physical and financial availability of alcohol. With the current restrictions on alcohol availability, it is postulated that, for the immediate future, the predominant scenario will likely be the second, while the distress experienced in the first may become more relevant in the medium‐ and longer‐term future. Monitoring consumption levels both during and after the COVID‐19 pandemic will be necessary to better understand the effects of COVID‐19 on different groups, as well as to distinguish them from those arising from existing alcohol control policies.     

Somatostatin receptor 1–5; expression profiles during rat development

Background

Somatostatin acts through five receptor subtypes (SSTRs 1–5). We aimed to investigate SSTRs mRNA expression and protein distribution in whole rat embryos, with special emphasis on the pancreas.

Material and methods

Rat embryos were collected on embryonal days 10, 11, 12, 14, 15, 17, 19, 21, and at birth. Presence of SSTRs was investigated with RT-PCR techniques and immunohistochemistry.

Results

There was no SSTR5 mRNA expression in the whole rat embryos. All SSTR1–5 proteins were observed at embryonal day 10, but the localization varied between the different subtypes. From day 11 to birth SSTRs protein presence increased with time in major structures such as skin and cartilage. It remained similar over time in the heart and liver. In the fetal pancreas mRNA expression of SSTR2 and 4 was detected at day 14, and there was an increase up to birth. Only SSTR1 protein co-localized to a higher extent with the islet hormones studied. SSTR2 was present in all islet endocrine cells except for β-cells. In contrast, the immunostaining for SSTR3–4 was co-localized with insulin and PP, and, finally, SSTR5 with glucagon and pancreatic polypeptide. In mRNA isolated from whole rat embryos SSTR1-2 and SSTR4 expression showed a peak at day 14, while SSTR3 mRNA was not present until day 15.

Conclusion

The present data suggest a role for SSTRs during the development of the rat embryo. Subsequent functional studies may elucidate regulatory roles of specific SSTRs for the growth and differentiation of the pancreas as well as other organs.     

Features of Everyday Life in Psychiatric Inpatient Care for Self-harming: An Observational Study of Six Women

This study aimed to describe the features of everyday life in psychiatric inpatient care as experienced by women who self-harm. Participant observations and informal interviews were conducted with six women and were subjected to qualitative content analysis. The major feature of everyday life in psychiatric inpatient care was ‘being surrounded by disorder’, which consisted of ‘living in a confusing environment, being subject to routines and rules that offer safety but lack consistency’ and ‘waiting both in loneliness and in togetherness’. The nursing staff spent minimal time with the patients and the women turned to each other for support, care and companionship.