Decreased TcR-CD3+ T cell numbers in healthy aged humans. Evidence that T cell defects are masked by a reciprocal increase of TcR-CD3- CD2+ natural killer cells

While there is accumulating evidence to indicate the presence of functional abnormalities in T cells from aged healthy humans, their cellular basis remains unclear. By using two-color immunofluorescence and multiparameter flow cytometry we show that (a) the number of peripheral blood antigen receptor-positive (TcR-CD3+) T cells is significantly lower in aged than in young adults; (b) the numbers of E-rosette-forming (CD2+) cells are maintained in the elderly due to a reciprocal increase in the frequency of TcR-CD3- cells, which constitute only a minor lymphocyte subpopulation in young adults, and (c) TcR-CD3-CD2+5- lymphocytes exhibit the phenotypic features of natural killer (NK) cells. By using functional assays we show the TcR-CD3-CD2+16+ lymphocytes are indeed NK cells because they are activated by and lyse NK targets. In contrast, they are unresponsive to either phytohemagglutinin or mitogenic CD2 monoclonal antibody stimulation, which in turn activates TcR-CD3+CD2+16- T cells. We conclude that the increase in TcR-CD3-CD2+ NK cells masks the T cell reduction in aged humans by normalizing CD2+ cell frequencies. However, NK cells cannot functionally substitute the thymus-derived lymphocytes they replace.     

Influence of age on iminodipropionitrile-induced vestibular and neurobehavioral toxicities in rats

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.     

HIV-1 p24 antigen testing in blood banks: results from Saudi Arabia

HIV-1 p24 antigen testing was introduced to increase sensitivity in the early detection of HIV infection in blood donors. Since the introduction of HIV-1 p24 antigen testing in Saudi Arabia, we have failed to detect a single positive case. Over a three-year period, only four indeterminates were detected out of 24,654 blood donors. All four proved negative by confirmatory testing. Based on this experience, we believe that resources would be better directed to pooled nucleic acid testing and that p24 serological testing should be abandoned.     

Immunomodulatory Effects of Dietary Polyphenols

Functional and nutraceutical foods provide an alternative way to improve immune function to aid in the management of various diseases. Traditionally, many medicinal products have been derived from natural compounds with healing properties. With the development of research into nutraceuticals, it is becoming apparent that many of the beneficial properties of these compounds are at least partly due to the presence of polyphenols. There is evidence that dietary polyphenols can influence dendritic cells, have an immunomodulatory effect on macrophages, increase proliferation of B cells, T cells and suppress Type 1 T helper (Th1), Th2, Th17 and Th9 cells. Polyphenols reduce inflammation by suppressing the pro-inflammatory cytokines in inflammatory bowel disease by inducing Treg cells in the intestine, inhibition of tumor necrosis factor-alpha (TNF-α) and induction of apoptosis, decreasing DNA damage. Polyphenols have a potential role in prevention/treatment of auto-immune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis by regulating signaling pathways, suppressing inflammation and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon-γ (IFN-γ)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune responses.     

Endocrine contribution to the sexual dysfunction in patients with advanced chronic kidney disease and the role of hyperprolactinemia

In this study, we investigated the prevalence of sexual dysfunction among males with advanced chronic kidney disease and the effect of treating hyperprolactinemia among these patients. In this prospective study, patients were assessed with history, physical examination, hormonal assessment, and two questionnaires, IIEF and AIPE. Patients with hyperprolactinemia received treatment with cabergoline 0.5 mg once per week for 6 months and were re-evaluated. A total of 102 patients were included in this study, 75 (73.53%) were on hemodialysis, 13 (12.75%) on peritoneal dialysis and 14 (13.73%) on medical treatment alone. Ninety (88.24%) patients had premature ejaculation, 85 (83.33%) had anything from mild-to-moderate-to-severe erectile dysfunction. The incidence of hypogonadism and hyperprolactinemia was 34.4%. Patients treated with cabergoline (n = 26) showed a significant increase in LH levels (p = .003) and a significant decrease in prolactin levels (p = .003). Testosterone levels and the incidence of erectile dysfunction or premature ejaculation did not improve significantly. There is a high incidence of sexual dysfunction among patients. Treatment of hyperprolactinemia is effective in correcting prolactin levels, but does not improve erectile dysfunction or premature ejaculation. Therefore, treating hyperprolactinemia is not an overall effective treatment for erectile dysfunction in these patients.     

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.     

Multi-Disciplinary Trauma Evaluation and Management Simulation (MD-TEAMS) training for emergency medicine and general surgery residents

BackgroundSuccessful trauma resuscitation relies on multi-disciplinary collaboration. In most academic programs, general surgery (GS) and emergency medicine (EM) residents rarely train together before functioning as a team.MethodsIn our Multi-Disciplinary Trauma Evaluation and Management Simulation (MD-TEAMS), EM and GS residents completed manikin-based trauma scenarios and were evaluated on resuscitation and communication skills. Residents were surveyed on confidence surrounding training objectives.ResultsResidents showed improved confidence running trauma scenarios in multi-disciplinary teams. Residents received lower communication scores from same-discipline vs cross-discipline faculty. EM residents scored higher in evaluation and planning domains; GS residents scored higher in action processes; groups scored equally in team management. Strong correlation existed between team leader communication and resuscitative skill completion.ConclusionMD-TEAMS demonstrated correlation between communication and resuscitation checklist item completion and communication differences by resident specialty. In the future, we plan to evaluate training-related resident behavior changes and specialty-specific communication differences by residents.