Monocyte-derived RANTES is intrinsically elevated in periodontal disease while MCP-1 levels are related to inflammation and are inversely correlated with IL-12 levels

Bacteria colonizing tooth surfaces are essential in the induction of an inflammatory response in the periodontal tissues, but do not cause periodontitis in everyone, implicating differences in the host immune response. These possible differences were studied using lipopolysaccharide (LPS)-stimulated whole blood cell cultures (WBCC), which revealed a down regulation of monocyte derived interleukin-12 (IL-12p70) in untreated periodontitis patients and an up regulation after therapy. IL-12p70 is a crucial factor in the differentiation of Th1 cell responses. Since CC chemokines are able to influence the T cell differentiation via cytokine secretion in antigen-presenting cells, the production of CC chemokines in periodontitis was evaluated. Therefore WBCC were stimulated with LPS from Escherichia coli for 18 h and the levels of IL-12p70 and CC chemokines were measured in the supernatants by ELISA. Untreated periodontitis patients released 2 fold more RANTES (regulated on activation normal T cell expressed and secreted) (P = 0.01) and lower levels of IL-12p70 in comparison to controls (P < 0.05). A trend towards higher levels of macrophage chemoattractant protein-1 (MCP-1) (P = 0.07) was also seen in untreated periodontitis patients; while similar levels of monocyte derived chemokine (MDC) and macrophage inflammatory proteins-1 alpha and -1 beta (MIP-1 alpha and -1 beta) were found. After periodontal therapy no changes were seen with regard to MDC, MIP-1 alpha, MIP-1 beta and RANTES, whereas the MCP-1 levels decreased (P < 0.05) and the IL-12p70 levels strongly increased (P < 0.01). The data showed a consistent inverse correlation between the levels of MCP-1 and IL-12p70, and their proportional changes after therapy correlated with the clinical inflammatory response after therapy. This indicates that the disease state regulates the release of IL-12p70 and MCP-1 in E. coli LPS-stimulated WBCC. In contrast, the persistent augmented levels of RANTES after therapy are suggestive for an intrinsic behaviour.     

Expression of apoptosis-related proteins and morphological changes in a rat tumor model of human small cell lung cancer prior to and after treatment with radiotherapy,carboplatin, or combined treatment

PURPOSE: In order to understand the apoptosis pathway in tumor cells, differences in cell morphology and expression of apoptosis-related proteins induced by radiation and/or chemotherapy, were investigated in a rat double tumor model comparing cisplatin-sensitive and -resistant human small cell lung cancer tumors. METHODS: The cisplatin-sensitive human small cell lung cancer cell line (GLC4) and its cisplatin-resistant subline (GLC4-CDDP) were each injected subcutaneously in a different hind limb of the rat. After 15-17 days, radiation (10 Gy), carboplatin (25 mg/kg, intraperitoneal), combined treatment, or no treatment was administered. In combined treatment, carboplatin was administered 24 h before radiation. Tumors were removed and fixed 72 h after carboplatin or 48 h after radiation. Paraffin-embedded slides were stained with hematoxylin/eosin for morphology. Expression of the apoptosis-related proteins p53, p21, Rb, bcl-2, bax, c-myc, Fas and Fas-L was assessed immunohistochemically. RESULTS: In the GLC4 tumor, carboplatin treatment increased tumor cell size, tumor cell size heterogeneity, and number of apoptotic tumor cells. After radiation and combined treatment, these changes were more pronounced and multinuclear giant cells were observed. In GLC4-CDDP tumors, minimal changes were detected after carboplatin. Following radiation slight increases in tumor cell size, tumor cell size heterogeneity and number of apoptotic tumor cells were observed. No multinuclear giant cells were seen. After combined treatment, GLC4-CDDP showed cellular changes comparable to those in GLC4 cells after radiation or combined treatment, but no giant cells were observed. Untreated, both tumors were equally positive for p53, bax, Fas, Fas-L, c-myc and negative for Rb. Contrary to GLC4, untreated GLC4-CDDP tumors showed no p21 and bcl-2 expression. After combined treatment, an increase in number of bcl-2 positive cells was found in GLC4-CDDP tumors. No p21 was induced in GLC4-CDDP by any treatment modality. In GLC4 tumors, p21 was induced by radiation alone. No further changes in protein expression were induced by any treatment in GLC4 tumors. CONCLUSION: Following therapy, morphological changes in cell size and cell size heterogeneity were more pronounced in GLC4 than in GLC4-CDDP tumors. However, morphological changes in GLC4-CCDP tumors after treatment indicate that carboplatin plus radiotherapy may be effective also in cisplatin resistant tumor cells. An increase in p21 in GLC4 after radiation might facilitate apoptosis. The increase in number of Bcl-2 positive cells after combined treatment and the consistently negative p21 status after any treatment in GLC4-CDDP may protect these tumor cells from apoptosis as a part of their resistance mechanism to cisplatin.     

A coherent pattern among social behavior, blood pressure, corticosterone and catecholamine measures in individual male rats

Behavioral and physiological responses of 18 chronically cannulated male TMD-S3 rats were assessed during various social interactions with conspecifics, both with and without the possibility for physical contact (social vs. psychosocial stimulation). Response magnitudes (behavior, blood pressure, plasma catecholamines) depend upon both the social environmental requirements (offense, defense, psychosocial stimulus following defense) and individual characteristics. The more competitive males generally reacted with higher responses of blood pressure and catecholamines than more passive rats. In addition, these competitive males had higher baseline levels of noradrenaline. The present experiment shows that male rats differ in the individual sympathetic tone and reactivity in relation to their behavior in a social environment.     

Older Chinese migrants in coronavirus pandemic: exploring risk and protective factors to increased loneliness

Older migrants may be one of the most vulnerable populations during the coronavirus pandemic, yet the degree of impact remains largely unknown. This study explores (1) the consequences of the coronavirus pandemic for older Chinese migrants in Belgium and the Netherlands in terms of increased loneliness and its risk factors (reduced in-person contact, decreased social participation, feelings of existential threat) and protective factors (increased non-in-person contact, more individual activities), and (2) which risk and protective factors have contributed to the incidence and prevention of higher loneliness levels. Using quantitative data of a survey among 98 Chinese migrants aged 50 years and older in Belgium (n = 84) and the Netherlands (n = 14), the findings first indicate that the coronavirus pandemic has a significant impact on older Chinese migrants’ lives. One in five experienced more loneliness. Second, reduced social participation (measured as less frequent participation in outdoor group activities) and financial insecurity (measured as experiencing financial difficulties) lead to higher than pre-pandemic loneliness levels. Problem-focused coping strategies (measured as increased non-in-person contact, via telephone or social media) and emotion-focused coping (measured as finding distraction through increased participation in individual activities) were not found to protect against increased loneliness in the pandemic. Two practical implications for loneliness interventions for older Chinese migrants are put forward. Organizing COVID-19-safe social participation activities and paying more attention to older Chinese migrants’ financial situation can be beneficial when addressing higher levels of loneliness due to the coronavirus pandemic.     

JM216-, JM118-, and cisplatin-induced cytotoxicity in relation to platinum-DNA adduct formation,glutathione levels and p53 status in human tumour cell lines with different sensitivities to cisplatin

The aim of this study is to establish anti-tumour potency of the new oral platinum drug JM216 and its metabolite JM118 in relation to the platinum (Pt)-DNA adduct formation, glutathione (GSH)-levels, and p53 status in human cancer cell lines with different sensitivities to cisplatin (CDDP). These parameters were studied in the CDDP sensitive human germ cell cancer cell line Tera and the small-cell lung cancer cell line GLC4 and their sublines with in vitro acquired CDDP resistance, Tera-CP and GLC4-CDDP, in a human ovarian cancer cell line transfected with mutant p53 (A2780/mt273) and with an empty vector as control (A2780/cmv), and in the intrinsic CDDP resistant human non-small-cell lung cancer cell line SW1573/S1 and colon carcinoma cell line Caco-2. Cytotoxicity was tested with the microculture tetrazolium (MTT)-assay. Pt-DNA adduct levels were assessed immunocytochemically. Quantitative analysis was performed by double fluorescence video microscopy. Results were correlated with GSH levels and p53 status of the cell lines. This study showed that both JM216 and JM118 can partially circumvent intrinsic and acquired resistance to CDDP. Drug-induced cytotoxicity only correlated negatively with GSH levels for JM216 and CDDP in the tested unselected cell lines. At equimolar basis, JM216 induced lower levels of Pt-DNA adducts in the various cell lines than JM118 and CDDP, whereas the JM118-induced amount and pattern of Pt-DNA adducts was comparable to CDDP. No difference in initial Pt-DNA adducts levels was observed between cell lines sensitive, acquired or intrinsic resistant to CDDP suggesting a Pt-resistance mechanism based on tolerance or increased repair, rather than decreased initial Pt-DNA adduct formation.     

Loneliness Among Older Lesbian,Gay, and Bisexual Adults: The Role of Minority Stress

Past research has consistently found that aging lesbians, gay men, and bisexuals (LGBs) are more apt to suffer from loneliness than their heterosexual counterparts. Data from the 2002 Gay Autumn survey (N = 122) were used to find out whether minority stress relates to higher levels of loneliness among older LGB adults in the Netherlands. We examined five minority stress factors: external objective stressful events, expectations of those events, internalized homonegativity, hiding and concealment of one’s LGB identity, and ameliorating processes. The results showed that greater insight into loneliness among older LGB adults was obtained when minority stress factors were considered. Older LGB adults who had experienced negative reactions, as well as aging LGBs who expected those reactions, had the highest levels of loneliness. Having an LGB social network buffered against the impact of minority stress. These minority stress processes added to the variance already explained by general factors that influenced levels of loneliness (partner relationships, general social network, physical health, and self-esteem). Interventions aimed at decreasing feelings of loneliness among older LGBs should be focused on decreasing societal homonegativity (to decrease the amount of negative and prejudiced reactions) and on the enhancement of social activities for LGB elderly.