Pathways to ischemic neuronal cell death: are sex differences relevant?

We have known for some time that the epidemiology of human stroke is sexually dimorphic until late in life, well beyond the years of reproductive senescence and menopause. Now, a new concept is emerging: the mechanisms and outcome of cerebral ischemic injury are influenced strongly by biological sex as well as the availability of sex steroids to the brain. The principal mammalian estrogen (17 β estradiol or E2) is neuroprotective in many types of brain injury and has been the major focus of investigation over the past several decades. However, it is becoming increasingly clear that although hormones are a major contributor to sex-specific outcomes, they do not fully account for sex-specific responses to cerebral ischemia. The purpose of this review is to highlight recent studies in cell culture and animal models that suggest that genetic sex determines experimental stroke outcome and that divergent cell death pathways are activated after an ischemic insult. These sex differences need to be identified if we are to develop efficacious neuroprotective agents for use in stroke patients.     

HLA-DRB1* GENE SEQUENCES IN HLA-DR4 POSITIVE AND NEGATIVE PATIENTS WITH RHEUMATOID ARTHRITIS

The second exon of the DRB1 gene encoding for the first domain of the HLA-DR β-chain was sequenced in 16 patients (10 DR4/DR1 positive, 6 DR4/DR1 negative) with seropositive rheumatoid arthritis (RA). We could confirm the strong association of susceptibility to RA with functionally equivalent conformations on otherwise distinct MHC molecules. At least one HLA-DR allele in all of the analysed DR4 or DR1 positive patients showed such an epitope with a minimal variability limited to residue 71. However, in HLA-DR4 and -DR1 negative patients such a similar epitope could not be detected.     

On the functionality of the visually deprived occipital cortex in early blind persons

In early blind mammals, the deprived visual cortex undergoes anatomical and functional alterations. Its functional role was investigated in the early human blind by using patterns of cortical activation as measured by scalp-recorded event-related slow negative DC potential shifts. The blind showed higher occipital negativity than did sighted persons both during a tactile reading task and a non-reading tactile control task. Results point to a possible role for the blind's visual cortex in tactile processes.     

Effect of bezafibrate during 4.5 years of treatment of hyperlipoproteinaemia

Bezafibrate in a dosage of 200 mg 3 times daily was given to 24 patients with type II A (n = 8), II B (n = 1) and IV (n = 15) hyperlipoproteinaemia for 4.5 years. In type II A the content of total cholesterol and that of low density lipoprotein in serum decreased by 10-23 and 11-34 percent over the years compared to pretreatment. In type IV the content of total triglycerides and that of very low density lipoprotein decreased by 28-39 and 38-52 percent, respectively, over the years. High density lipoprotein cholesterol increased in both types. The "atherogenic index" was reduced by the drug. The effect remained through the 4.5 years of treatment. Compliance to the drug was good. Changes in safety laboratory parameters were minor and reversible. No subjective side-effects occurred and no cases of gallbladder disease or cancer were noted. It is concluded that bezafibrate is a safe, convenient and effective serum lipid-lowering drug suitable for the use in primary and secondary prevention of atherosclerotic disease.     

Image quality assurance in x-ray diagnostic units. Information on DIN 6868 standard series

The Working Group for Standardisation justifies and comments on the establishment of a standard series for image quality assurance in X-ray diagnostic services (DIN 6868). In order to promote compliance with these standards, the users are given some background information on the structure of the standard series and on the recommended procedures to be followed. The definitions for the various hierarchically arranged tests, such as constancy test, status test, acceptance test as well as a definition for the term "base-line image quality" are explained.     

Surgical treatment of radiogenic prostate-urethra-rectum fistula

Five patients with postirradiation prostatic urethrorectal fistules after treatment of localized carcinoma of the prostate by external beam and interstitial implantation with 125I seeds were treated by two different methods. Previous defunctioning colostomy and suprapubic tube diversion alone failed to close the lesion. Three patients underwent anterior rectal resection and restoration by deep colo-anal anastomosis. Two more patients were treated by anterior "pull-through-resection" with mucosectomy of the distal rectal stump and colo-anal sleeve anastomosis as described by Parks. In addition, omentum was used to fill the pelvis. This operative technique is favoured due to improved results.     

Spontaneous association between opioid receptors and GTP-binding regulatory proteins in native membranes: specific regulation by antagonists and sodium ions

High affinity GTPase in membranes from NG108-15 cells was differentially affected by opioid competitive antagonists; one type of antagonist [( N,N'-diallyl-Tyr1-Aib2,3]Leu-enkephalin) reduced the basal rate of GTP hydrolysis, whereas a second type (MR 2266) produced no changes. The inhibitory effect of the "active" antagonist was stereospecifically reversed by the "inactive" antagonist, indicating that it was receptor mediated. This suggests that part of basal GTPase activity in this system results from a spontaneous interaction between opioid receptors and GTP-binding proteins (G proteins) and that some antagonists exhibit negative intrinsic activity by hindering such an interaction. The inhibitory effect of the antagonist was minimal in the presence of Na+ and maximal when Na+ was replaced by K+ in the reaction. When the ratio [Na+]/[K+] was progressively increased at constant [Cl-], total GTPase activity (i.e., net difference between activity stimulated by agonist and that inhibited by antagonist) did not change, but the activity measured in the absence of ligand was selectively decreased. Thus, Na+ does not alter the total proportion of G proteins that can be activated by ligand-occupied receptors and instead regulates the interaction between receptor and G protein in the absence of ligand. Upon examination of several opioid agonist and antagonists, we found an inverse relation between the intrinsic activity (either negative or positive) of each ligand and the sensitivity to Na+ of the GTPase elicited upon occupation of the receptor by that ligand. Sodium-mediated and ligand-mediated regulations of GTPase had identical requirements for Mg2+ [( Mg2+]free greater than 10 microM), and were both abolished with a similar potency by pertussis toxin. There was no effect of Na+ on the basal rate of GTP hydrolysis of Gi/Go purified from bovine brain. However, addition of these proteins to membranes prepared from cells that had been previously exposed to pertussis toxin partially restored both receptor- and sodium-mediated regulations of GTPase in parallel and in a concentration-dependent fashion. We conclude that sodium ions play a key role in the mechanism underlying the spontaneous interaction between "empty" receptors and G proteins in intact membranes.     

The acceptance of SARS-CoV-2 rapid antigen self-testing: A cross-sectional study in China

Compared with the nucleic acid amplification test (NATT), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid antigen self-testing (RAST) has advantages in speed and convenience. However, little is known about people's acceptance and influencing factors for SARS-CoV-2 RAST. A cross-sectional study was conducted from April 21 to 30, 2022 in China. The χ² test and multivariate logistic regressions were used to identify the influencing factors. The structural equation model was used to test the extended protective motivation theory (PMT) model hypotheses. Among the total of 5107 participants, 62.5% were willing to accept the SARS-CoV-2 RAST. There were significant differences in acceptance among different residences (p < 0.001), educational level (p < 0.001), occupation (p < 0.001), monthly income (p < 0.001), travel frequency (p < 0.05), and feelings about NATT (p < 0.001). Response efficacy (β = 0.05; p = 0.025) and self-efficacy (β = 0.84; p < 0.001) had a positive effect, while response cost showed a negative effect (β = −0.07; p < 0.001). The public's major concerns about SARS-CoV-2 RAST are its reliability, testing method, price, and authority. Overall, a moderate intention to use SARS-CoV-2 RAST was found among the Chinese population. The extended PMT can be used for the prediction of intention to accept the RAST. We need to take measures to increase people's acceptance of SARS-CoV-2 RAST.