Preliminary Analysis of the Anti-biofilm Efficacy of Manuka Honey on Extended Spectrum Β-lactamase Producing Escherichia Coli Tem-3 and Klebsiella Pneumoniae Shv18, Associated with Urinary Tract Infections

open access articleUrinary Tract Infections (UTIs) are one of the most common infections in the UK and many other parts of the world. The prevalence of the Extended Spectrum β-Lactamases (ESBLs) producing UTIs, combined with their ability to form a bio film, has significantly risen and is limiting therapeutic options. This study investigated the anti-bio film activity of Manuka honey on two ESBL producing pathogens, Escherichia coli TEM-3 and Klebsiella pneumonia SHV18, commonly found in UTIs. The ESBL production was confirmed by the double disk synergy method used to confirm the ESBL production. The antibacterial activity of Manuka honey was determined using the agar well diffusion method. The Minimum Inhibitory Concentration (MIC) was established using serially diluted honey ranging from 50% to 1.56%. The effect of Manuka honey on the pathogen bio films was analysed using the Tissue Culture Plate method, with an established MIC and under 24h incubation with the honey. The results indicated that K. pneumonia SHV18 is a stronger bio film producer than E. coli TEM 3. 50% (w/v) MIC Manuka honey appears to fully prevent the plank tonic growth of both strains. A significant reduction of 81% of the E. coli TEM3 (p < 0.001) and 52% of the K. pneumonia SHV18 (p = 0.001) bio film biomass was observed. The E. coli bio films were found to be more sensitive to the 50% (w/v) honey dilution than those produced by K. pneumonia. The study indicated the anti-bio film potency of Manuka honey and its potential to become an alternative treatment for the ESBL producing pathogens associated with UTIs

Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men

Leydig cell number and function decline as men age, and low testosterone is associated with all “Western” cardio-metabolic disorders. However, whether perturbed androgen action within the adult Leydig cell lineage predisposes individuals to this late-onset degeneration remains unknown. To address this, we generated a novel mouse model in which androgen receptor (AR) is ablated from ∼75% of adult Leydig stem cell/cell progenitors, from fetal life onward (Leydig cell AR knockout mice), permitting interrogation of the specific roles of autocrine Leydig cell AR signaling through comparison to adjacent AR-retaining Leydig cells, testes from littermate controls, and to human testes, including from patients with complete androgen insensitivity syndrome (CAIS). This revealed that autocrine AR signaling is dispensable for the attainment of final Leydig cell number but is essential for Leydig cell maturation and regulation of steroidogenic enzymes in adulthood. Furthermore, these studies reveal that autocrine AR signaling in Leydig cells protects against late-onset degeneration of the seminiferous epithelium in mice and inhibits Leydig cell apoptosis in both adult mice and patients with CAIS, possibly via opposing aberrant estrogen signaling. We conclude that autocrine androgen action within Leydig cells is essential for the lifelong support of spermatogenesis and the development and lifelong health of Leydig cells.—O’Hara, L., McInnes, K., Simitsidellis, I., Morgan, S., Atanassova, N., Slowikowska-Hilczer, J., Kula, K., Szarras-Czapnik, M., Milne, L., Mitchell, R. T., Smith, L. B. Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men

Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency

Over the past 5 yr several inactivating mutations in the LH receptor gene have been demonstrated to cause Leydig cell hypoplasia, a rare autosomal recessive form of male pseudohermaphroditism. Here, we report the identification of two new LH receptor mutations in a compound heterozygous case of complete Leydig hypoplasia and determine the cause of the signaling deficiency at a molecular level. On the paternal allele of the patient we identified in codon 343 a T to A transversion that changes a conserved cysteine in the hinge region of the receptor to serine (C343S); on the maternal allele a T to C transition causes another conserved cysteine at codon 543 in trans-membrane segment 5 to be altered to arginine (C543R). Both of these mutant receptors are completely devoid of hormone-induced cAMP reporter gene activation. Using Western blotting of expressed LH receptor protein with a hemagglutinin tag, we further show that despite complete absence of total and cell surface hormone binding, protein levels of both mutant LH receptors are only moderately affected

Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency

OBJECTIVE: Discontinuation of growth hormone (GH) therapy on completion of linear growth may adversely affect bone mineral density (BMD) in young adults with childhood-onset GH-deficiency (GHD). In the present study, we analyzed the impact of GH treatment on bone in young adults with GHD. METHODS: BMD at the lumbar spine (L2-L4), total hip, and total body was measured at baseline and after 24 months in a cohort of young adults (18-25 years; n=160) with severe GHD treated with GH during childhood who were randomized to GH (n=109) or no treatment (n=51) in a multicenter, multinational, open-label study. GH starting doses (0.2 mg/day (males), 0.4 mg/day (females)) were increased after 1 month to 0.6 mg/day (males) and 0.9 mg/day (females) and then to 1.0 mg/day (males) and 1.4 mg/day (females) at 3 months for the remainder of the study. RESULTS: After 24 months, lumbar spine BMD had increased significantly more in GH-treated patients than in controls (6 vs 2%; estimated treatment difference; 3.5% (95% confidence interval, 1.52-5.51) P<0.001). GH also had a significant positive effect on total hip BMD (P=0.015). Total body BMD was unchanged from baseline (P=0.315). CONCLUSIONS: In young adults treated for childhood-onset GHD, there is a beneficial effect of continued GH treatment on BMD in adult life. Twenty-four months of GH treatment in these young adults was associated with an estimated 3.5% greater increase in BMD of the lumbar spine compared with controls

Supplementary Material for: A Case of Two Sisters Suffering from 46,XY Gonadal Dysgenesis and Carrying a Mutation of a Novel Candidate Sex-Determining Gene STARD8 on the X Chromosome

Identification of novel genes involved in sexual development is crucial for understanding disorders of sex development (DSD). Here, we propose a member of the START domain family, the X chromosome<i> STARD8,</i> as a DSD candidate gene. We have identified a missense mutation of this gene in 2 sisters with 46,XY gonadal dysgenesis, inherited from their heterozygous mother. Gonadal tissue of one of the sisters contained Leydig cells overloaded with cholesterol droplets, i.e., structures previously identified in 46,XY DSD patients carrying mutations in the <i>STAR</i> gene encoding another START domain family member, which is crucial for steroidogenesis. Based on the phenotypes of our patients, we propose a dual role of <i>STARD8 </i>in sexual development, namely in testes determination and testosterone synthesis. However, further studies are needed to confirm the involvement of <i>STARD8</i> in sexual development

Serum variations of anti-mullerian hormone and total testosterone with aging in healthy adult Iranian men: A population-based study

Literature proves anti-mullerian hormone (AMH) and total testosterone (TT) as two important reproductive hormones in male development, however evidence regarding age variations of these hormones is lacking.To estimate the normal serum AMH values and to assess the age-specific TT levels in men aged 30-70, we conducted the present population-based study.A total of 831 healthy eligible men, aged 30-70 years, were recruited from Tehran Lipid and Glucose study cohort. Centiles for AMH were estimated according to the exponential normal 3-parameter model. The parametric method of Royston available in general software was applied for the first time to estimate the age-specific AMH and TT percentiles of 5th, 10th, 25th, 50th, 75th, 90th and 95th.Mean AMH level was 6.93, ranging from 0.1 to 40.1 ng/ml. Serum AMH concentrations followed a steady reduction with increasing age. Mean TT level was 4.8, ranging from 0.44 to 11.4 ng/ml.A measurable serum concentrations of AMH in healthy males throughout lifespan with variations, based on age, confirming a slight age-related AMH decline. Fractional polynomial (FP) regression models revealed that the mean and standard deviation (SD) of the TT were not associated with age, so the percentiles estimated were not age-specific.We presented a nomogram of age-specific AMH values in a healthy cohort of Iranian men. This finding might have clinical importance in dealing hormonal disorders in men