Anti-inflammatory effects of a titanium-peroxy gel: role of oxygen metabolites and apoptosis

Polymorphonuclear neutrophils (PMN) are among the first inflammatory cells to arrive at an implant interface, where they encounter with the foreign material and may produce reactive oxygen species (ROS). During the interaction between titanium and ROS, titanium-peroxy (Ti-peroxy) compounds may be formed. We used a Ti-peroxy gel, made from titanium and hydrogen peroxide, to study the effects of Ti-peroxy compounds on PMN. In the absence of serum, the Ti-peroxy gel decreased the oxidative response of PMN to yeast and PMA and reduced PMN apoptosis without inducing necrosis. These effects could not be ascribed to the release of hydrogen peroxide from the Ti-peroxy gel, because a steady-state hydrogen peroxide producing system failed to mimic the effects of the gel. The effects were similarly unaffected when PMN were preincubated with beta(2)-integrin antibodies, questioning the involvement of adhesion molecules. Nevertheless, when a filter was used to separate the Ti-peroxy gel from the cells, the gel effect on PMN life span was abolished, pointing to a contact-dependent mechanism. In the presence of serum, the Ti-peroxy gel had no effect on the PMN oxidative response and life span, but appeared rather inert. In summary, this study demonstrates that the Ti-peroxy gel has potentially anti-inflammatory properties through a combined peroxide and physical contact effect, supporting the notion that interactions between titanium and inflammatory cells are responsible for the good performance of titanium in vivo.     

Interpopulation variability among Panstrongylus megistus (Hemiptera: Reduviidae) from Brazil

Comparisons were made among Panstrongylus megistus (Burmeister) from three areas of Brazil (Bahia, Minas Gerais, and Santa Catarina), where populations differ with regard to their degree of association with human dwellings. The following characters were studied: morphology of the eggs and the male genitalia; morphometry of the head and thorax; isoenzyme profile; enzymatic activity of the alpha-glycerophosphate dehydrogenase (alpha-GPDH); and cytogenetics. In general, differences were observed in the weight, diameter, and length of the egg among Bahia, Minas Gerais, and Santa Catarina populations. Differences were not observed in the architecture of the egg exochorion. The size of the median process of the pygophore of the male genitalia of individuals from Bahia differed from the other two populations. The Minas Gerais population presented the largest number of denticles in the endosome process. The morphometry of the head and thorax differentiated Santa Catarina from the Bahia and Minas Gerais populations. Phosphoglucomutase (EC 5.4.2.2., PGM) was the only enzyme out of 11 that showed polymorphism; the population from Minas Gerais was most polymorphic, whereas the population from Santa Catarina was monomorphic. Study of the alpha-GPDH activity and cytogenetics did not reveal differences among the three populations. Analysis of all the characters studied together with information on these three populations from previous publications allowed a phenogram to be constructed. Two distinct groups were evident, one represented by Santa Catarina and the other by Bahia and Minas Gerais. Considering the greater variability of the Minas Gerais and Bahia populations, we propose the inclusion of these states within the area of origin of P. megistus.     

The majority of human CD3 epitopes are conferred by the epsilon chain

Transgenic mouse T cells expressing the human CD3 chain bindthe majority (29/36) of monoclonal antibodies (mAbs) specificfor human CD3. A proportion of these mAbs are also able to recognizeisolated CD3 in a soluble, recombinant form. Thus, CD3 can confermost CD3 epitopes on the TCR-CD3 complex, but many determinantsmay require assembly of the complex for their formation. A numberot mAbs did not recognize -transgenic T cells and probably needother CD3 subunits for binding. CD3-specific mAbs from eachof the three groups defined here, as well as mAbs directed againstthe TCRß heterodimer, are all able to activate T cells.Therefore mAb attachment at several different sites on the TCR-CD3complex can give rise to activation signals. This suggests thatthe cross-linking function of mitogenic antibodies may be theirmost significant property, rather than the perturbation of aparticular ‘functional epitope’.     

The effect of a 1-deoxynojirimycin derivative on post-prandial blood glucose and insulin levels in healthy black and white volunteers

Summary BAY m1099 (a 1-deoxynojirimycin derivative) is a glucose analogue which is an -glucosidase inhibitor. Its effects on post-prandial blood glucose and insulin levels was compared with a placebo in 12 healthy male volunteers (6 Blacks and 6 Whites). It produced a similar, significant depression of post-prandial blood glucose and insulin leveles when the groups were assessed separately and when the data were pooled. Although blood insulin levels in Whites were higher than in Blacks, as previously reported, the difference was not statistically significant and did not appear to influence the response to the drug. BAY 1099 produced no objective or subjective untoward effects and appears to warrant further investigation as an adjuvant to dietary control of diabetes mellitus.     

Validation of a screening test for alcohol use,the Russian Federation

ObjectiveTo validate a Russian-language version of the World Health Organization’s Alcohol Use Disorders Identification Test (AUDIT).MethodsWe invited 2173 patients from 21 rural and urban primary health-care centres in nine Russian regions to participate in the study (143 declined and eight were excluded). In a standardized interview, patients who had consumed alcohol in the past 12 months provided information on their sociodemographic characteristics and completed the Russian AUDIT, the Kessler Psychological Distress Scale and the Composite International Diagnostic Interview to identify problem drinking and alcohol use disorders. We assessed the feasibility of administering the test, its internal consistency and its ability to predict hazardous drinking and alcohol use disorders in primary health care in the Russian Federation.FindingsOf the 2022 patients included in the study, 1497 were current drinkers with Russian AUDIT scores. The test was internally consistent with good psychometric properties (Cronbach’s α : 0.842) and accurately predicted alcohol use disorders and other outcomes (area under the curve > 75%). A three-item short form of the test correlated well with the full instrument and had similar predictive power (area under the curve > 80%). We determined sex-specific thresholds for all outcomes, as non-specific thresholds resulted in few women being identified.ConclusionWith the validated Russian AUDIT, there is no longer a barrier to introducing screening and brief interventions into primary health care in the Russian Federation to supplement successful alcohol control policies.     

Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection

Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 treatment should be explored.     

Oesophageal and other cancer patterns in four selected districts of the Transkei, Southern Africa:1985-1990

New data regarding the incidence of oesophageal and other cancers during the period 1985-1990 are reported for all clinics and hospitals in four selected districts of Transkei, Southern Africa i.e. Kentani, Butterworth, Lusikisiki and Bisana. Active and passive methods were used to obtain the hospital-based cancer registry data. The mean annual number of cancer cases recorded for the period 1985-1990 was 292. Age-standardised incidence rates (ASIR, African standard) for all recorded cancer were 81.4 and 52.6/100,000 for males and females respectively. Histopathological examination of 52.6% of recorded tumors revealed that 67.3% were squamous carcinomas, 21.7% adenocarcinomas and the remainder non-epithelial neoplasm. Cancer of the oesophagus (OC) was the most frequently recorded cancer and accounted for the 46.5% of the cases with mean ASIR of 46.7 and 19.2/100,000 for males and females respectively. The male/female ratio was 2.4:1. The highest mean ASIR per annum for OC in males (55.6/100,000) occurred in Kentani and in females (22.3/100,000) in Lusikisiki, whereas the lowest rates in both sexes (37.0 and 11.7/100,000 respectively) occurred in Bizana. Comparison of the OC rates in the four districts of Transkei during 19985-1990 with previous reported trends, confirms a consistently high rate in the south-western districts of Kentani during the past 35 years and progressively increasing rates in the north-eastern districts of Bizana and Lusikisiki. These results have profound implications for further epidemiological and aetiological studies on OC in Transkei, but we need to be corroborated by data form other sources such as statistics on histologically diagnosed cancer in Transkei by districts in the South African National Cancer Registry. The second most frequent recorded cancer among males was liver cancer with a mean annual ASIR of 6.0/ 100,000 and male:female ratio of 3:1. The most frequent recorded cancer among females was cervical cancer with a mean annual ASIR of 20.9/100,000 followed by OC (19.2/100,000) and breast cancer (5.8/100,000).