Effect of Female Sex Hormones on the Immune Response against Chlamydia abortus and on Protection Conferred by an Inactivated Experimental Vaccine in a Mouse Model

Mice are valuable models extensively used to test vaccine candidates against Chlamydia abortus and to clarify immunopathological mechanisms of the bacteria. As this pathogen has the ability to reactivate during pregnancy, it is important to deepen the knowledge and understanding of some of the effects of female hormones on immunity and vaccination. This study is aimed at describing the role of sex hormones in the pathology of OEA during chlamydial clearance using ovariectomised mice and also gaining an understanding of how 17β-oestradiol or progesterone may impact the effectiveness of vaccination. Animals were treated with sex hormones and infected with C. abortus, and the kinetics of infection and immune response were analysed by means of bacterial isolation, histopathology, and immunohistochemistry. In a second phase of the study, protection conferred by an experimental vaccine after hormone treatment was assessed. Oestradiol showed a stimulatory effect on the immune response during infection, with a more efficient recruitment of macrophages and T-cells at the infection site. Furthermore, after vaccination, oestradiol-treated animals showed a stronger protection against infection, indicating that this hormone has a positive effect, stimulating a specific memory response to the pathogen.

Effects of plant growth regulators and growing media on propagation and field establishment of Stevia rebaudiana: a medicinal plant of commerce

Background Stevia rebaudiana is an economically important medicinal plant that has generated interest among the growers and pharmacologists in terms of its industrial or pharmaceutical value. For the mass production of the seedlings, easy and convenient techniques are lacking while, micro propagation was reported promising but still out of reach at farm level. The unavailability of quality planting materials due to non-viable seeds is restricting its mass commercial scale cultivation. The present study was therefore attempted to standardize the plant growth regulators and growing media to standardize the vegetative propagation protocol through cuttings for its mass multiplication in Terai region of West Bengal, India. Methods Growing media (soil, FYM, saw dust and sand) as sole and in combination and growth hormones (IAA, IBA and NAA in different concentration and a commercial formulation i.e. Totoroot© with different exposure time) were compared with control (i.e. sole soil and no hormone treatment, respectively) to standardize the nursery protocol of Stevia. Results Sand used as sole was found the best growing media for survival and growth of cuttings while, cuttings treated with commercial growth hormone formulation for 5 mins was best. Cuttings treated with commercial growth hormone formulation performed significantly better in the field with respect to survival, growth and production of leaves. Conclusion The study recommends the use of sole sand media and commercial growth hormone formulation with 5 mins exposure time for mass nursery production of Stevia cuttings in Terai zone of West Bengal due to their better performance both in the nursery and after transplanting in the field.

Individualized Growth Hormone Treatment - Using Two Different Prediction Models in a Clinical Setting

BackgroundDiagnosing growth hormone deficiency (GHD) can be challenging; hence, prediction models on growth outcome from growth hormone (GH) treatment have shown to be useful. We aim to compare the accuracy of the more readily available KIGS (Pfizer International Growth Study) prediction model to the previously clinically validated Gothenburg model.MethodsPrepubertal children with GHD who started GH treatment at Queen Silvia Children’s Hospital between 2004 and 2016 were considered for the study. Exclusion criteria were short stature due to syndrome, chronic disease, oncology disease, or known bad adherence. Growth predictions were made according to the Gothenburg model and the KIGS model. Growth data from birth until one year after start of GH treatment were collected from medical charts. Predicted height and observed height were then compared. ResultsA total of 123 children, 47 girls (38%) and 76 boys (62%) were included, with a mean age of 5.71 (±1.81 SD) years at start of GH treatment. The Pearson correlation of predicted first-year growth versus growth outcome were r = 0.990 for the Gothenburg model and r = 0.991 for the KIGS model. Studentized residuals were 0.10 ± 0.81 SD and 0.03 ± 0.96 SD, respectively, for the models. The comparison between the two models showed r = 0.995.ConclusionThe Gothenburg model and the KIGS model are equally accurate at predicting height outcome from GH treatment for our study cohort. We therefore promote the use of either model in clinical settings.

Growth in Children With Noonan Syndrome and Effects of Growth Hormone Treatment on Adult Height

ObjectivesGrowth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children.MethodsRetrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with PTPN11 mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement.ResultsANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (p<0.001), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from −3.10 ± 0.84 to −2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH.ConclusionsrhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of PTPN11 gene and in the less common genotypes.

Cardiovascular safety of growth hormone treatment in Noonan syndrome: real-world evidence

Objective: To assess cardiovascular (CV) safety of growth hormone (GH) treatment in patients with Noonan syndrome (NS) in clinical practice. Design: Two observational, multicentre studies (NordiNet® IOS and the ANSWER Program) evaluating long-term effectiveness and safety of GH in >38,000 paediatric patients, of which 421 had NS. Methods: Serious adverse events, serious adverse reactions (SARs), and non-serious adverse reactions (NSARs) were reported by the treating physicians. CV comorbidities at baseline and throughout the studies were also recorded. Results: The safety analysis set comprised 412 children with NS (29.1% females), with a mean (standard deviation) baseline age of 9.29 (3.88) years, treated with an average GH dose of 0.047 (0.014) mg/kg/day during childhood. CV comorbidities at baseline were reported in 48 (11.7%), most commonly pulmonary valve stenosis and atrial septal defects. Overall, 22 (5.3%) patients experienced 34 safety events. The most common were the NSARs: headache (eight events in seven patients) and arthralgia (five events in three patients). Two SARs occurred in one patient (brain neoplasm and metastases to spine). No CV safety events were recorded in patients with NS. Five CV comorbidities in five patients were reported after initiation of GH treatment: three cases of unspecified CV disease, one ruptured abdominal aortic aneurysm and one pulmonary valve stenosis. Conclusions: GH treatment had a favourable safety profile in patients with NS, including those with CV comorbidities. Prospective studies are warranted to systematically assess the safety of GH treatment in patients with Noonan syndrome and CV disease.

Accessory corpus luteum regression during pregnancy II: reproductive outcomes

The objective of this study was to evaluate the effect of accessory corpus luteum (CL) induction on fertility in dairy cows. On day 5 after artificial insemination (AI), lactating Holstein cows were assigned unequally to receive gonadotrophin-releasing hormone treatment (GnRH) (n = 641) or no treatment (control; n = 289). Cows had their blood sampled for progesterone (P4), and ovaries were scanned by ultrasound on days 5, 12, 19, 26, 33, 47, and 61 after AI. Pregnancy diagnosis was performed on days 26, 33, 47, and 61. On day 12, cows treated with GnRH were allocated to ipsilateral (n = 239) or contralateral (n = 241) groups based on the side of accessory CL formation relative to previous ovulation. Accessory CL cows had greater P4 than controls. In total, 52.7% (78/148) of pregnant cows in contralateral group had accessory CL regression earlier (<day 33; 30.8%) or later (days 33–61; 69.2%) in pregnancy with coincident decrease in P4. No cows with ipsilateral accessory CL underwent regression. There was no difference in pregnancy/AI among groups. Cows with contralateral accessory CL that underwent early regression had greater pregnancy loss (30%) than controls (10%), or cows with ipsilateral CL (3%) or contralateral CL with either later or no regression (12%). Cows with ipsilateral accessory CL had lower pregnancy loss than controls. In conclusion, elevating circulating P4 by the induction of accessory CL, particularly ipsilateral CL, increases P4 and reduces pregnancy loss. However, contralateral accessory CL that undergoes regression before day 33 of pregnancy has increased pregnancy loss, possibly due to an abrupt decrease in P4 at a pivotal period of pregnancy (days 26–33).