Nucleoside peptides. 10. Synthesis and T-cell immunostimulatory properties of certain peptide derivatives of 6-azacadeguomycin

Several amino acid and peptide conjugates of 6-azacadeguomycin (6-amino-1-beta-D-ribofuranosyl-4,5-dihydro-4-oxopyrazolo[3,4-d]py rimidine- 3-carboxylic acid, 2) have been prepared in good yields, via a two-step procedure involving 1-hydroxybenzotriazole and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride mediated coupling of 2 with an appropriately protected amino acid or peptide, followed by ammonolysis. Thus, condensation of 2 with L-phenylalanine methyl ester, glycine ethyl ester, and L-glutamic acid diethyl ester gave the corresponding protected linear nucleoside peptides (3, 5 and 7, respectively). Subsequent ammonolysis of 3, 5 and 7 furnished L-phenylalanine amide (4), glycine amide (6) and L-glutamic acid diamide (8) conjugates of 6-azacadeguomycin, respectively. Saponification of 7 gave the corresponding L-glutamic acid derivative 9. A similar coupling of 2 with L-phenylalaninyl-N epsilon-nitro-L-arginine methyl ester trifluoroacetate and subsequent ammonolysis (after catalytic hydrogenation) gave L-phenylalaninyl-L-arginine amide conjugate (12) of 6-azacadeguomycin. Compounds 2, 4, 6, 8, 9, and 12 were evaluated for their ability to potentiate T-cell responses to plant mitogens, in comparison with cadeguomycin (1). Compounds 4, 6, and 9 exhibited an increase in the T-cell proliferation in a dose-dependent manner.     

Host immunity to mosquitoes: effect of antimosquito antibodies on Anopheles tessellatus and Culex quinquefasciatus (Diptera: Culicidae).

Rabbit antibodies to antigens derived from the tissues of sugar-fed Anopheles tessellatus Theobald were fed to An. tessellatus and Culex quinquefasciatus Say in blood meals. These antibodies tended to reduce the number of eggs produced by An. tessellatus, but had no effect on the fecundity of Cx. quinquefasciatus. Ingestion of the rabbit antibodies did not detectably affect the mortality of An. tessellatus but increased the mortality of Cx. quinquefasciatus. The results provide preliminary evidence for the potential of antimosquito antibodies to disrupt the physiology of mosquito vectors and indicate the need for further studies with high-titer, monospecific antibodies against the relevant target antigens.     

Characterisation of an inhibitory monoclonal antibody-defined epitope on a malaria vaccine candidate antigen.

A monoclonal antibody that recognizes a recently characterised 45-kDa merozoite surface antigen of the human malaria parasite Plasmodium falciparum inhibits the growth of the asexual blood stages of the parasite in vitro. The corresponding epitope has been determined by testing the reactivity of the antibody with sequentially overlapping octapeptides. A synthetic peptide containing the epitope elicits antibodies that react with the native antigen. Epitope mapping in this manner is useful in the design of synthetic vaccines against malaria.     

Surface T- and B-cell markers on murine lymphomas and plasmacytomas

Seven murine lymphomas and three plasmacytomas were examined for the distribution of the theta antigen, immunoglobulin determinants, the receptor for Fc portion of antigen—antibody complexes and the receptor for the third component of complement. The theta-bearing tumours lacked C3 and Fc receptors and easily detectable surface immunoglobulin. The theta-negative lymphomas, while being morphologically lymphocytic, lacked all but the Fc receptors. One of the plasmacytomas possessed clearly detectable surface immunoglobulin. All three lacked the receptors for Fc and C3.     

Effects of added bioactive glass on the setting and mechanical properties of resin-modified glass ionomer cement

In this study, the effects of added bioactive glass on the basic setting properties of a commercially available resin-modified glass ionomer cement were investigated with respect to setting time, mechanical strength, and setting mechanism. It was found to be clinically acceptable whether the setting time was extended or shortened depending on the type of bioactive glass added. The compressive strength of the set cement containing the bioactive glass decreased and was much higher when compared with the conventional type glass ionomer cement containing bioactive glass. The Fourier-transform infrared and 13C CP/MAS-NMR spectroscopies revealed that the extent of the acid-base reaction was larger in the cements containing bioactive glass than in the commercial resin-modified glass ionomer cement because of its high basicity in the bioactive glass. The 27Al MAS-NMR showed that crosslinking of the carboxylates in the polymeric acid by Al proceeded less in the cement containing the bioactive glass.     

Adherence to COVID-19 Nutrition Guidelines Is Associated with Better Nutritional Management Behaviors of Hospitalized COVID-19 Patients

Good nutritional support is crucial for the immune system to fight against coronavirus disease 2019 (COVID-19). However, in the context of a pandemic with a highly transmissible coronavirus, implementation of nutrition practice may be difficult. A multicenter electronic survey involving 62 dieticians was conducted, in order to understand barriers associated with dieticians’ adherence to nutrition guidelines for hospitalized COVID-19 patients in Indonesia. 69% of dieticians felt under stress when performing nutrition care, and 90% took supplements to boost their own immunity against the coronavirus. The concerns related to clinical practice included a lack of clear guidelines (74%), a lack of access to medical records (55%), inadequate experience or knowledge (48%), and a lack of self-efficacy/confidence (29%) in performing nutritional care. Half (52%) of the dieticians had performed nutrition education/counseling, 47% had monitored a patient’s body weight, and 76% had monitored a patient’s dietary intake. An adjusted linear regression showed that guideline adherence independently predicted the dieticians’ nutrition care behaviors of nutrition counselling (ß: 0.24 (0.002, 0.08); p = 0.04), and monitoring of body weight (ß: 0.43 (0.04, 0.11); p = 0.001) and dietary intake (ß: 0.47(0.03, 0.10); p = 0.001) of COVID-19 patients. Overall, adherence to COVID-19 nutrition guidelines is associated with better nutritional management behaviors in hospitalized COVID-19 patients.     

A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review

Clomiphene, a selective oestrogen receptor modulator, has been utilised in managing male sub-fertility since 1967. Numerous controlled and uncontrolled studies have been published regarding the efficacy of clomiphene citrate in male sub-fertility cohorts. Although the primary intention of treating men with clomiphene citrate is to improve sperm parameters and testosterone levels, some studies have reported paradoxical decline in semen parameters. The information available on decline in sperm parameters following treatment with clomiphene is sparse. We conducted a systemic review using PubMed, Embase, Cochrane Library and Scopus databases for original studies reporting adverse effects of clomiphene citrate therapy on sperm parameters. This systematic review includes 384 men from 11 different studies that reported adverse effects of clomiphene citrate therapy. Of the men included in these studies, 19%, 21%, 17% and 24% of clomiphene-treated men demonstrated a decrease in sperm count, concentration, motility and total motile sperm count respectively. In up to 17% of patients, deterioration of semen parameters did not recover following discontinuation of therapy. In the future, more studies should report on this aspect so the magnitude of this effect can be more clearly understood.     

How defective spermatogenesis affects sperm DNA integrity

Spermatogenesis is the essential process to maintain and promote male fertility. It is extraordinarily complex with many regulatory elements and numerous steps. The process involves several cell types, regulatory molecules, repair mechanisms and epigenetic regulators. Evidence has shown that fertility can be negatively impacted by reduced sperm DNA integrity. Sources of sperm DNA damage include replication errors and causes of DNA fragmentation which include abortive apoptosis, defective maturation and oxidative stress. This review outlines the process of spermatogenesis, spermatogonial regulation and sperm differentiation; additionally, DNA damage and currently studied DNA repair mechanisms in spermatozoon are also covered.