Inhibition of prostaglandin synthesis reduces cyclic AMP levels and inhibits chondrogenesis in cultured chick limb mesenchyme

The present study investigated effects of inhibiting the synthesis of prostaglandins (PGs) on cyclic AMP concentrations and chondrogenesis in cultured chick limb mesenchyme. Indomethacin produced concentration-dependent inhibition of both PGE₂ synthesis and chondrogenesis over a concentration range of 50--200 M. Half maximal inhibition of PGE₂ was achieved with 50 M concentrations of the drug which also produced visibly reduced amounts of cartilage matrix in cell cultures as evaluated by Alcian green staining on day 6 of culture. The inhibitory effects of indomethacin on chondrogenesis were largely reversed by addition of 1 mM dibutyryl cAMP, indicating that cells could still respond to cyclic AMP stimulation. Endogenous levels of cyclic AMP, which increased by 6 fold during the six days of culture in control cells, did not increase significantly from dissociated cells at the time of plating (day 0) in indomethacin-treated cultures. The results indicate that inhibition of the prechondrogenic rise in PGE₂ concentrations in limb mesenchyme prevents the increase in cyclic AMP levels which occur during this same period resulting in inhibition of chondrogenesis. The data provide further support for the hypothesis that PGE₂, through its effects on the adenylate cyclase-cAMP system, plays an important role in the differentiation of cartilage.     

On the valency of incomplete anti-Rh antibodies

The univalency concept of the mechanism responsible for the failure of incomplete antibodies to produce direct agglutination of appropriate untreated red cells has been investigated. Artificially produced univalent (hybrid) 7S antibodies were found to differ in serologic behaviour from incomplete anti-Rh antibodies of the same molecular size. The data suggest that the so-called `univalent' anti-Rh antibody molecule is bivalent.     

Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL-1.

Using a sensitive IL-1-dependent T cell clone we estimated interleukin 1 (IL-1)-like activity in a variety of synovial fluids (SF). Although we demonstrate that SF contains potent inhibitors of endogenous and exogenous IL-1 we were able to estimate that samples from rheumatoid arthritis, osteoarthritis and other arthritides contain the equivalent of tens or hundreds of picograms of IL-1 per millilitre, when compared to a standard IL-1 preparation. Although there was some correlation between these results and those obtained using a radio-immunoassay (RIA) for IL-1 beta, the RIA indicated that IL-1 was present in the nanogram range. The results suggest that the importance of inhibitors of IL-1 in SF merits particular attention and that it is also important to consider the bioactivity of cytokines which may be detected by physical methods.     

Inhibitory effects of opioids in a circular muscle-myenteric plexus preparation of guinea-pig ileum

Summary The actions of opioids were examined in a strip preparation of the external muscle and myenteric plexus of the guinea-pig ileum cut parallel to the circular muscle. Contractions of the circular muscle induced by electrical stimulation of myenteric neurons were depressed in a concentration-dependent manner by the mu agonists, morphine and DAGO, and by the kappa agonist, U-50,488H. The concentrations of morphine, DAGO and U-50,488H which depressed nerve-mediated contractions by 50% (IC₅₀) were 86 nM, 11 nM and 5.0 nM, respectively. The equilibrium dissociation constants (K _D) for naloxone as an antagonist of the inhibitory effects of DAGO and of U5-0,488H were 5.6 nM and 29.4 nM, respectively. In contrast to the potent inhibitory effects of mu and kappa agonists, the delta-selective agonist, d-Pen-l-Pen, produced only weak inhibition of nerve-mediated contractions. Even at a concentration of 3 M, there was less than 50% inhibition, which was not antagonised by the delta receptor antagonist, ICI 174864. The experiments indicate that both mu and kappa opioid receptors are present on the myenteric neurons supplying the circular muscle and that delta receptors are either absent or ineffectively activated. Send offprint requests to S. M. Johnson     

Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract

Summary Eight smooth muscle preparations from the stomach, small intestine and large intestine of the guinea-pig were used to compare apamin's actions in reducing the effectiveness of transmission from enteric inhibitory nerves and in reducing responses to inhibitory agonists ,-methylene ATP, VIP and isoprenaline. The effects of apamin on inhibitory reflexes in the ileum and colon were also evaluated. Apamin had little or no effect on responses to VIP and isoprenaline in any region, but consistently and substantially reduced responses to ,-methylene ATP. Responses to stimulation of enteric inhibitory neurons were substantially reduced by apamin in the antrum circular muscle, ileum longitudinal and circular muscle, taenia coli and distal colon longitudinal muscle, but it was ineffective in the fundus circular muscle, proximal colon longitudinal muscle and distal colon circular muscle. It caused a small reduction of the relaxation of the ileal circular muscle caused reflexly by distension, but did not modify the similar descending inhibitory reflex in the circular muscle of the colon. It is concluded that apamin can be used to distinguish two types of non-noradrenergic transmission from enteric inhibitory nerves to gastrointestinal muscle. Furthermore, neither VIP nor ATP can be the sole transmitter chemical released from enteric inhibitory neurons throughout the gastrointestinal tract.     

COVID-19 among LGBTQ+ individuals living with HIV/AIDS: psycho-social challenges and care options

Prolonged social isolation during the COVID-19 lockdown has adversely impacted the mental, social, and physical wellbeing of the global populace. Coping with mental and physical stressors amidst the global lockdown is especially strenuous for the Lesbian, Gay, Bisexual, Transgender, and more (LGBT+) community, who are frequently subjected to social stigma and minority stress. Systematic stigma and discrimination place LGBT+ individuals at higher risk for deleterious behaviors, such as substance abuse (e.g., injection drug use, smoking, alcohol) and risky sexual practices (e.g., anal/vaginal/oral sex). Maladaptive coping behaviors consequently increase the chances of HIV/AIDS risk among LGBT+ individuals, compared to heterosexual individuals. LGBT+ individuals Living with HIV/AIDS perpetually face higher rates of unemployment, income disparity, and intimate partner violence. Prolonged home confinement, and impaired accessibility to healthcare, legal, and criminal justice services during lockdown may deplete the quality of life of LGBT+ individuals Living with HIV/AIDS. Therefore, it is critical that multidisciplinary service providers, including health professionals, employers, social services providers, educational institutions and community organizations, move toward online service delivery, so that homebound HIV-positive LGBT+ individuals are secured with a wide range of care options. Non-judgemental, tele-counseling may bridge the gap to mental health services. Community clinics catering to HIV-positive and/or LGBT+ clients may consider precociously supplying essential amenities, such as Preexposure (PrEP)/postexposure prophylaxis (PEP), condoms, emergency contraception, and sterile needles. Lastly, efforts directed at the sustenance of at-risk/HIV-positive LGBT+ health should persevere, even after the pandemic.     

Pediatric Group Care: A Systematic Review

Maternal and Child Health Journal - To describe characteristics and outcomes of Group Well-Child Care programs and provide recommendations for future research. Informed by Preferred Reporting Items...     

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.     

Trends and Outcomes in Simultaneous Liver and Kidney Transplantation in Australia and New Zealand

AimRates of simultaneous liver and kidney transplantation (SLKT) have increased, but indications for SLKT remain poorly defined. Additional data are needed to determine which patients benefit from SLKT to best direct use of scarce donor kidneys.MethodsData were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) database for all SLKT performed until the end of 2017. Patients were divided by pretransplant dialysis status into no dialysis before SLKT (preemptive kidney transplant) and any dialysis before SLKT (nonpreemptive). Baseline characteristics and outcomes were compared.ResultsBetween 1989 and 2017, inclusive, 84 SLKT procedures were performed in Australia, of which 24% were preemptive. Preemptive and nonpreemptive SLKT recipients did not significantly differ in age (P = .267), sex (P = .526), or ethnicity (P = .870). Over a median follow-up time of 4.5 years, preemptively transplanted patients had a statistically equivalent risk of kidney graft failure (hazard ratio (HR) 1.83, 95% confidence interval [CI]: 0.36-12.86, P = .474) and all-cause mortality (HR 1.69, 95% CI: 0.51-5.6, P = .226) compared to nonpreemptive patients. Overall, 1- and 5-year survival rates for all SLKTs were 92% (95% CI: 86-96) and 60% (95% CI: 45-75), respectively.ConclusionKidney graft and overall patient survival were similar between patients with preemptive kidney transplant and those who were dialysis dependent.