Injection Of Hydrocortisone Research Articles

Phenylethanol glycosides from Cistanche tubulosa improved reproductive dysfunction by regulating testicular steroids through CYP450-3β-HSD pathway.

Cistanche tubulosa (Schenk) R. Wight has been used frequently in traditional folk medicine for treatment of male sexual dysfunction (MSD). Phenylethanol glycosides, the main components of C. tubulosa, possess a variety of pharmacological activities due to their multiple properties. However, the underlying mechanism by which phenylethanol glycosides from C. tubulosa (CPhGs) regulates testicular steroids has not been elucidated to date. This study is to determine whether CPhGs promotes the reproductive functions of mice through CYP450-3β-HSD pathway of testosterone synthesis. The major compositions of C. tubulosa (CPhGs) were quantified by high performance liquid chromatography (HPLC). The model of reproductive injury in mice were induced by injection of hydrocortisone (HCT). Different doses of CPhGs (72, 145 and 289mg/kg) and testosterone propionate (TP, positive control drug) were administrated intragastrically for 14d. The reproductive functions (erectile incubation period, capture and ejaculation incubation period, number of captures and ejaculations) and organ weights (testicle, epididymis, seminal vesicle and penis) were then determined. The levels of luteinizing hormone and testosterone in serum were quantified by radioimmunoassay. The key enzymes in testosterone synthesis pathways such as steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc/CYP11A1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the testis were assessed by immunofluorescence (IF) staining or/and Western blot (WB) analysis. The results illustrated that the low dose of CPhGs (72mg/kg) had no significant protective effect against the reproductive injury caused by HCT, while the moderate dose of CPhGs (145mg/kg) improved the damaged reproductive ability and the declined levels of luteinizing hormone and testosterone in the model mice (P<0.001, P<0.05, respectively). In particular, high dose of CPhGs (289mg/kg) was most effective in improving HCT-induced changes in body weight (P<0.01), reducing the incubation period of the erectile (P<0.001), capture (P<0.05) and ejaculation (P<0.01), and increasing the number of captures and ejaculations (P<0.01, P<0.05, respectively). The weights of testcle, epididymis, seminal vesicle and penis (P<0.001, P<0.01, P<0.01, P<0.001, respectively) were improved by high dose of CPhGs. The levels of testosterone and its upstream luteinizing hormone were up-regulated by high dose of CPhGs (P<0.001). Meanwhile, the expressions of the key steroidogenic enzymes including CYP11A1 and 3β-HSD were significantly up-regulated after CPhGs treatment (P<0.001), demonstrated that CPhGs exerted the effect through enhancing testosterone biosynthesis via CYP450-3β-HSD pathway. CPhGs could significantly protect against HCT-induced deleterious reproductive dysfunction and testis injury. The protective effects were exerted by up-regulating synthesis of testosterone via the CYP450-3β-HSD pathway in Leydig cells.

50 Years Ago in TheJournalofPediatrics: Neonatal Septicemia

Gotoff SP, Behrman RE. J Pediatr 1970;76:142-53. Gotoff and Behrman defined neonatal septicemia as generalized bacterial infection documented by positive blood culture in the first 4 weeks of life; it was categorized as early-onset sepsis (EOS) and late-onset sepsis (LOS; after 72 hours). A presumptive diagnosis was based on clinical evidence. Infected amniotic fluid was a major source of neonatal septicemia. The most common organisms causing EOS were Escherichia coli, Streptococcus faecalis, and Staphylococcus aureus; beta hemolytic streptococci were also reported. Organisms isolated in LOS included Pseudomonas, Proteus, Klebsiella-Aerobacter, and S aureus. First-line antibiotic therapy for EOS and LOS were ampicillin plus kanamycin and methicillin/oxacillin plus kanamycin, respectively, for 7-10 days. Whole blood as a plasma expander, injection sodium bicarbonate injection, and glucose infusion were being given for shock. Hydrocortisone injection and isoproterenol infusion as vasopressors were indicated in nonresponders. Intravascular coagulation was managed with fresh heparinized whole blood and heparin injection. Fifty years later, neonatal sepsis remains the third-leading global cause of death under age 5 years. The subdivision into EOS and LOS is now universally accepted. The major causative organisms for EOS in developed countries are group B streptococci and E coli. More than 50% of cases of LOS are caused by coagulase-negative staphylococci (CONS), and the remainder are caused by gram-negative organisms. In developing countries, common organisms causing neonatal sepsis include S aureus, E coli, and Klebsiella species. Absolute neutrophil count, C-reactive protein, and procalcitonin are increasingly being used to support the diagnosis. Urine culture, gastric aspirate examination, and body surface cultures are not routinely recommended. Today, first-line antibiotics for EOS are ampicillin/benzyl penicillin plus aminoglycoside (gentamicin) for 7-10 days. For LOS, combinations of third-generation cephalosporins plus aminoglycoside, ampicillin plus gentamicin, or vancomycin/flucloxacillin plus gentamicin/cefotaxime are recommended, based on local resistance patterns and whether hospital-acquired or community-acquired.1World Health Organization Antibiotic use for sepsis in neonates and children: 2016 evidence update.https://www.who.int/selection_medicines/committees/expert/21/applications/s6_paed_antibiotics_appendix4_sepsis.pdfDate accessed: July 6, 2019Google Scholar, 2Clinical Excellence CommissionNewborn antibiotic guideline for early- and late-onset sepsis during birth episode of care.http://www.cec.health.nsw.gov.au/data/assets/pdf_file/0009/348597/Newborn-Antibiotic-Guide∼or-early-and-late-onset-sepsis-during-birth-episode-of-care-Revised-June-2018.pdfDate: 2018Date accessed: July 3, 2019Google Scholar Treatment is given for 7-10 days except for meningitis, which is treated for 21 days. Fresh-frozen plasma is recommended for intravascular coagulation. Newer therapies in the pipeline include immunoglobulins, colony-stimulating factors, anti–tumor necrosis factor, and interleukin antagonists.

Enhancement of Kidney Invigorating Function in Mouse Model by Cistanches Herba Dried Rapidly at a Medium High Temperature.

Cistanches Herba is a popular Traditional Chinese Medicine and functional food that is used to treat kidney yang deficiency (KYD) in China. In this study, we investigated the effects of different drying methods for Cistanches Herba on kidney invigoration and yang strengthening. We established a mouse model of KYD by intraperitoneal injection of hydrocortisone for 8 days. We dried slices of Cistanches Herba in the sun, in the shade, in a microwave, or in an oven at 40°C, 60°C, 80°C or 100°C, then prepared and administered extracts to the mice by gastric gavage. We measured and evaluated the echinacoside (ECH) and acteoside (ACT) contents of the extracts, as well as the mice's body weight; testicular, epididymal, hepatic, and renal coefficients; and semen quality. All the Cistanches Herba extracts, obtained using different drying techniques, improved symptoms of KYD diagnosis in mice. Among them, treatments with Cistanches Herba dried in a microwave and dried in an oven at 100°C had the best therapeutic effects. Our results suggested that the higher the total content of ECH and ACT in Cistanches Herba extracts, the better the effects of kidney invigoration and yang strengthening. In addition, shorter drying times at higher temperatures lead to the highest recoveries of active components, and Cistanche dried in the sun at a medium-high temperature can improve sperm quality in mice.

Differential antipredatory responses in the tuco-tuco (Ctenomys talarum) in relation to endogenous and exogenous changes in glucocorticoids.

Glucocorticoids participate in the behavioral and physiological responses generated under stressful circumstances coming from different sources-physical and/or psychological. In mammals, the increases of these hormones are mediated by the activation of the hypothalamic-pituitary-adrenal axis. This response occurs after exposure to novel and unpredictable situations that lead to the loss of homeostasis, for example, a direct encounter with predators or their cues. However, the relationship between the physiological and behavioral responses is still a complex issue in vertebrates. We evaluate the effects of an experimental manipulation of glucocorticoid levels on the generation of the behavioral and physiological response to stress by predation in the subterranean rodent C. talarum. We found that when tuco-tucos encountered predator cues-fur odor, and largely, immobilization-they responded physiologically by secreting cortisol. This response was accompanied by an associated behavioral response. However, when the increase in plasma cortisol originated exogenously by the injection of cortisol, a behavioral response was not observed. Finally, inhibition of glucocorticoids' synthesis was effective in weakening the behavioral effects produced by immobilization. In conclusion, in tuco-tucos, predator cues act as stress factors that trigger differential increases in plasma cortisol and a behavioral response associated with the appearance of anxiety states.

Effect of intravenous injection of hydrocortisone and lidocaine 2% on pain after propofol injection: a double-blind randomized clinical trial

Effect of intravenous injection of hydrocortisone and lidocaine 2% on pain after propofol injection: a double-blind randomized clinical trial

Prehospital Management of Acute Addison Disease: Audit of Patients Attending a Referral Hospital in a Regional Area.

ContextAdrenal crisis (AC) causes morbidity and mortality in patients with Addison disease [primary adrenal insufficiency (PAI)]. Patient-initiated stress dosing (oral or parenteral hydrocortisone) is recommended to avert ACs. Although these should be effective, the continued incidence of ACs remains largely unexplained.MethodsAudit of all attendances between 2000 and 2017 of adult patients with treated PAI to one large regional referral center in New South Wales, Australia. Measurements were those taken on arrival at hospital.ResultsThere were 252 attendances by 56 patients with treated PAI during the study period. Women comprised 60.7% (n = 34) of the patients. The mean age of attendees was 53.7 (19.6) years. Nearly half (45.2%, n = 114) of the patients had an infection. There were 61 (24.2%) ACs diagnosed by the treating clinician. Only 17.9% (n = 45) of the hospital presentations followed any form of stress dosing. IM hydrocortisone was used prior to presentation 7 (2.8%) attendances only. Among patients with a clinician-diagnosed AC, only 32.8% (n = 20) had used stress dosing before presentation. Vomiting was reported by 47.6% (n = 120) of the patients but only 33 (27.5%) of these attempted stress dosing and 5 patients with vomiting used IM hydrocortisone. The number of prior presentations was an independent predictor of use of stress doses [1.05 (1.01, 1.09)].ConclusionDose-escalation strategies are not used universally or correctly by unwell patients with PAI; many patients do not use IM or subcutaneous hydrocortisone injections. Previous hospital treatment increases the likelihood of stress dosing, and hospital attendance offers the opportunity for reinforcement of prevention strategies.

A prospective comparative study of functional outcome following arthroscopic debridement and hydrocortisone injection vs arthroscopic debridement and hyaluronicacid injection for the treatment of early primary osteoarthritis knee

Objective: Early knee osteoarthritis in all cases, lead to degenerative medial meniscus lesions which are visible in MRI as chondral defects. As a result, it is difficult to distinguish between unstable meniscus and early osteoarthritis which leads to symptomatic knee pain. Hence, we decided to study improvement athroscopic meniscectomy and injecting Hyaluronic acid or Hydrocortisone in cases of degenerative ruptures of the medial meniscus with changes of early stage medial compartment knee osteoarthritis. Materials and Methods: 60 consecutive cases of early OA Knee of non traumatic origin were studied. They were given treatment of arthroscopic lavage and randomly administered hydrocortisone or hyaluronic acid. The WOMAC score was obtained and compared from immediate post-op period to upto 6 months. Result: In our study on patient undergoing arthroscopic debridement of osteoarthritis knee with Inj. Hydrocortisone improvement in WOMAC score was from 50.97% to 43.81%, totally an improvement of WOMAC score 7.2% while those undergoing arthroscopic debridement of osteoarthritis knee with Inj. Hyaluronic acid improvement in WOMAC score was from 51.25% to 37.1%, totally an improvement in WOMAC score of around 15%. Conclusion: Joint lavage by arthroscopy in combination with either intra-articular steroid injection or intra-articular hyaluronic acid injection provides significant improvement in osteoarthritis knee patient. Data suggests that, those patient who underwent arthroscopic debridement and injection of hydrocortisone had symptomatic improvement at early follow up more than those of the hyaluronic acid, while arthroscopic debridement of osteoarthritis knee and injection of hyaluronic acid performed better at longer follow up. Keywords: WOMAC score, Hyaluronan, Osteoarthritis.

274-LB: The Anti-inflammatory Effects of Insulin and Hydrocortisone Combination in Obese Subjects

Glucocorticoids have been used as the major class of anti-inflammatory agents for over 60 years. However, they have well known side effects including weight gain, adiposity, muscle loss, osteoporosis and diabetogenicity. We have recently described the induction of specific pro-inflammatory genes by a single large dose of hydrocortisone (HC) in normal weight subjects. Since our group discovered the anti-inflammatory actions of insulin, we have now hypothesized that a combination of insulin with a high dose of a HC may neutralize the proinflammatory effects of HC and offer a safe anti-inflammatory combination. Eight obese subjects (BMI:31-46 kg/m2, age: 29-63 years, 3 females) were randomized into a cross over study to be injected in two separate visits (a week apart) with 300 mg of HC (?60 mg prednisolone) intravenously with or without an infusion of 2U/h of insulin with 5% dextrose for 8 hours. HC injection alone induced a significant anti-inflammatory effect including suppression of CCR-2 (by 54±8%), IL-4 (by 68±14%) and TNF-α (by 35±10%) expression in mononuclear cells (MNC). However, the HC injection also induced an increase in the expression of HMG-B1, TLR2, TLR4, TLR9, JNK-1 and RANK-L (by 43±12%, 57±9%, 62±17%, 69±15%, 89±19% and 61±11% over the baseline, respectively, P&amp;lt;0.05 for all). Plasma glucose and FFA concentrations also increased significantly following the HC injection alone. Insulin infusion along with the HC injection further suppressed the expression of CCR-2, TNF-α and IL-4 in MNC and completely inhibited the HC induced increases in FFA concentrations and in HMG-B1, TLR-2, TLR-9 and RANK-L expression (p&amp;lt;0.05 vs. HC alone). In addition, insulin infusion not only inhibited the HC induced increases in JNK-1 and TLR4 expression but also suppressed levels below baseline (by 27±14% and 22±10%, p&amp;lt;0.001 vs. HC alone). Thus, the infusion of insulin at a low dose with a high dose of HC or other corticosteroids may constitute an ideal anti-inflammatory cocktail in the in- patient setting. Disclosure P. Dandona: Advisory Panel; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. H. Ghanim: None. M. Batra: None. K. Green: None. S. Abuaysheh: None. R. Katkar: None.

Multiple Sclerosis in Pregnant and Postpartum Women

This case study involves a patient with multiple sclerosis (MS) and her care during the postpartum period. MS is a chronic disease of the central nervous system. A common feature is that the body’s immune system starts attacking healthy tissue by mistake. Specifically, the body attacks the myelin sheath that protects nerve cells. In 2017, a 29-year-old gravida 5, para 5 woman, while participating in a MS medication trial, was found to be pregnant. During her stay in the hospital, she received gabapentin for MS and was scheduled to have a rituximab infusion before discharge. Many women with MS will have an exacerbation of symptoms during the postpartum period. In this case, after coordinating care among postpartum, neurology, management, obstetric providers, and staff, we were able to transport the patient to our high-risk unit on Postpartum Day 4 for rituximab infusion. A neurological assessment, mobility, and pain assessment were performed by nursing and neurology staff on arrival in the unit. The woman was alert and knew who she was, where she was, and the approximate time (i.e., oriented ×3); a 10/10 headache was noted, and decreased strength–sensation was noted in the extremities. The patient was placed on cardiac monitoring and premedicated 30 min before the administration of rituximab. A hydrocortisone injection was ordered to have at bedside in case of an adverse reaction. Medication titration was based on the patient’s toleration to treatment. The infusion rate was started at 50 mg/hr and increased by 50 mg/hr every 30 min. The patient started to feel “flu like” symptoms at a rate of 100 mg/hr, so dosing was held there. When infusion completed, the patient reported increased mobility and decreased pain. She was transferred back to the postpartum unit for discharge to home. The patient was educated on hand washing and infection prevention, advised to avoid walking while holding her newborn when she felt unsteady, and informed of the need of assistive devices for walking at home if need be. Contact information for neurology and transfusion center follow-up information were provided.

Cortisol regulation of Na+, K+-ATPase β1 subunit transcription via the pre-receptor 11β-hydroxysteroid dehydrogenase 1-like (11β-Hsd1L) in gills of hypothermal freshwater milkfish, Chanos chanos

Hypothermal stress changes the balance of osmoregulation by affecting Na+, K+-ATPase (Na-K-ATPase) activity or inducing modulation to epithelium permeability in fish. Meanwhile, cellular concentrations of cortisol can be modulated by the pre-receptor enzymes 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-Hsd1 and 2). In fish, increasing levels of exogenous cortisol stimulate Na+ uptake via specific interaction with cortisol. This study investigated cortisol effects on expression of Na-K-ATPase subunit proteins and activity in gills of milkfish under hypothermal stress and revealed that the plasma cortisol contents as well as gill 11β-hsd1l and na-k-atpase β1 mRNA abundance were decreased in fresh water (FW) milkfish. Meanwhile, in the seawater (SW) milkfish, the plasma cortisol contents and gill 11β-hsd1l and na-k-atpase β1 mRNA abundance was increased under hypothermal stress. On the other hand, the abundance of 11β-hsd2 mRNA increased in both FW and SW. In addition, 11β-hsd1l expression increased in FW milkfish but decreased in SW milkfish after cortisol injection. Accordingly, the results that gill Na-K-ATPase activity of FW milkfish was affected by environmental temperatures as well as cortisol-dependent Na-K-ATPase β1-subunit levels might be due to increased expression of 11β-hsd1l that elevated intracellular cortisol contents. In hypothermal SW milkfish, decreasing abundance of Na-K-ATPase β1 protein due to reduced expression of 11β-hsd1l was found after cortisol injection. Thus, under hypothermal stress, 11β-HSD1L in FW milkfish gills was used to modulate cortisol and the following effects on increasing the transcription of Na-K-ATPase β1 protein.

PRS7 SEVERE AND UNCONTROLLED ASTHMA IN SOUTH KOREA: PROPORTION OF EXACERBATION LEADING TO HOSPITALIZATION OR INTENSIVE CARE UNIT ADMISSION

To estimate proportion of exacerbation leading to hospitalization or intensive care unit (ICU) admission in patients with severe and uncontrolled asthma in Korea. This study was performed using nationally representative data, Health Insurance Review and Assessment Service-National Patient Sample 2016, that included medical and pharmacy claims of approximately 1.4 million patients. To define patients and exacerbation, we used the recommendation of European Respiratory Society/American Thoracic Society and Global Initiative for Asthma guideline. We included patients with severe and uncontrolled asthma defined as subjects satisfying all conditions as follows: (1) ≥1 claim of asthma diagnosis (ICD-10 code J45/J46); (2) ≥1 claim of inhaled corticosteroid [ICS]); (3) ≥1 claim of additional controller or ≥180 days use of add-on low dose oral corticosteroids (OCS); and (4) ≥2 exacerbations or ≥1 exacerbation leading to hospitalization or ICU admission. Additional controller included LABA, leukotriene modifiers, theophylline, and tiotropium. Low dose OCS was defined as ≤7.5 mg/day prednisolone (or equivalent). Exacerbation was defined as outpatient visit, emergency department visit, hospitalization, or ICU admission with asthma diagnosis with corticosteroids bursts (defined as >30 mg/day prednisolone for >3 days or 200 mg hydrocortisone injection). Proportion of exacerbation leading to hospitalization or ICU admission was estimated as dividing the number of exacerbation episode with hospitalization or ICU admission by the number of exacerbation episode in patients with severe and uncontrolled asthma. Among eighty patients (with 138 exacerbation episodes) with severe and uncontrolled asthma, the mean age was 57.65 years, and 53.75% were women. The proportion of exacerbation leading to hospitalization or ICU admission was 53.62%. Of the exacerbations leading to hospitalization or ICU admission, the proportion of exacerbation leading to ICU admission was 13.51%. Among patients with severe and uncontrolled asthma, the occurrence of exacerbation requiring hospitalization or ICU admission was relatively high. Effective management strategy is needed.

SAT-391 Perioperative Glucocorticoid Therapy for Patients with Adrenal Insufficiency: Dosing Based on Hydrocortisone Pharmacokinetic Data

Background: Perioperative hydrocortisone (HC) therapy for patients with adrenal insufficiency (AI) vary from one institution to another and recommendations are not based on definitive data. Although the necessary HC dose is unknown, we utilized recent data documenting normal periop HPA function1 as a guide to assess HC substitution therapy in patients with AI. Goals: Examine the impact of 2 HC regimens on clinical symptoms and serum cortisol levels in subjects with documented AI, receiving chronic physiologic replacement. Methods: HC was administered for 48 hrs to 145 subjects with AI (37 with primary and 108 had central disease) undergoing surgical procedures (abdomen/ pelvis/ chest/ ortho) requiring general anesthesia. Oral HC (20 mg) was given 2-3 hrs before while IV therapy was started at intubation. Two regimens were randomly tested in patients with similar demographics and similar surgical procedures. One group (n=77) received 15mg HC every 6 hrs for 24 hours then dosing was adjusted as clinically necessary. A second group (n=68) received 25mg HC every 6 hrs for 24 hrs followed by 15 mg every 6 hrs for 24 hrs. Cortisol levels were determined frequently after the first and second HC injections during the first 24 hrs and at 36 and 48 hrs in the second groups. Results: There were no clinical evidence of AI during the peri-op period and all were discharged home. Baseline cortisol levels were 16.1±4.9 ug/dL. One hr after the first 15 and 25 mg HC doses, cortisol levels were 38.9±6.7 and 65.4±14 ug/dL, respectively (P<0.001). Nadir cortisol levels at 6 hrs in these patients were 10.8±4 and 19.9±5.5 ug/dL (P<0.001) respectively. The nadir serum cortisol levels after the second HC dose (13.8±3 VS 26.7±5 ug/dL) were higher (<0.01) than those obtained after the first dose. Patients receiving 15 mg HC had cortisol levels always >7.8 ug/dL while those who received 25 mg had levels >11.9 ug/dL. Both HC regimens resulted in cortisol levels that fell within, and were often higher than those observed in subjects with normal HPA. The calculated cortisol t1/2 after the first 25 mg dose (3.1±0.3 hrs) was higher (P<0.01) than that obtained after the 15 mg (2.6± 0.4 hrs) dose. Similarly, for both HC doses, cortisol t1/2 after the second dose was slightly higher than that determined after the first dose (P<0.01). Summary and Conclusions: A HC dose of 20 mg orally followed by 15 mg IV every 6 hrs is sufficient to raise serum cortisol levels in patients with AI to levels similar to those observed in subjects with normal HPA function. The 25 mg every 6 hrs dose may be of help in patients with prolonged and more extensive surgical procedures. A HC regimen of 25 mg every 6 hrs for 24 hrs followed by 15 mg every 6 hrs resulted in cortisol levels that are consistently similar or above those observed in critically-ill subjects. The data calls into question the current practice of using excessive peri-op doses of HC.

Emergency treatment of adrenal crisis with prednisone suppositories: a bioequivalence study in female patients with Addison's disease.

ObjectivePatients with adrenal insufficiency (AI) need to adapt their glucocorticoid replacement under stressful conditions to prevent adrenal crisis (AC). Prednisone (PN) suppositories are used for emergency treatment. Pharmacokinetics of 100 mg PN suppositories after vaginal or rectal administration was evaluated.DesignSingle-center, open-label, sequence-randomized, cross-over, bioequivalence study.MethodsTwelve females with primary AI were included. Comparison of pharmacokinetics after vaginal and rectal administration of 100 mg PN suppositories. Main outcome measures: bioequivalence (Cmax: maximum plasma concentration of prednisolone; AUC0 –360: area under the plasma concentration curve of prednisolone from administration to 360 min), adrenocorticotropin (ACTH) levels, safety and tolerability. Comparison of ACTH-suppressive effect with subcutaneous and intramuscular administration of 100 mg hydrocortisone.ResultsVaginal administration of PN suppositories was not bioequivalent to rectal administration: Cmax and AUC0–360 were significantly lower after vaginal compared to rectal administration: 22 ng/mL (109%) vs 161 ng/mL (28%), P < 0.001; 4390 ng/mL * min (116%) vs 40,302 ng/mL * min (26%), P < 0.001; (mean (coefficient of variation), respectively). A suppression of ACTH by >50% of baseline values was observed 149 min (32%) after rectal PN administration; after vaginal PN administration, the maximum decrease within 360 min was only 44%. Adverse events were more frequent after vaginal administration and mainly attributable to the glucocorticoid deficit due to inadequate vaginal absorption. The ACTH-suppressive effect was more pronounced after parenteral hydrocortisone compared to rectal or vaginal PN.ConclusionVaginal administration of PN suppositories in the available form is not useful for prevention of AC. Pharmacokinetics after rectal use of PN show inferiority compared to available data on parenteral glucocorticoids. In adrenal emergencies, hydrocortisone injection should be the first choice.

Newborn resuscitation practices and paucity of resuscitative devices in Nigeria; a call to action.

Neonatal resuscitation is a method of preventing morbidities & mortality from asphyxia. Up to 85% of facilities in sub-Saharan Africa lack supplies or skilled personnel for neonatal resuscitation. Relative to the place of birth and the skill of the birth attendant, a variety of resuscitative practice are employed to make babies cry instead of helping the baby breathe. Many painful procedures are applied when the baby is unable to cry after birth in the absence of a health care worker trained in bag-mask ventilation. To ascertain the resuscitation practices in communities lacking bag-mask-valve devices. Surveys on the resuscitation practices during NISONM annual community outreach and mENCC trainings for four consecutive years in different geopolitical zones of the country. Spanking of the baby usually in the upside down position (>90%), body massage with hot compress or salicylate containing balms, herbal concoctions, injection hydrocortisone or crystalline penicillin were used. There is an urgent need to address the issue of training on bag-mask ventilation and provision for frontline healthcare workers in Nigeria as a neonatal mortality reduction strategy.

Acute kidney injury induces dramatic p21 upregulation via a novel, glucocorticoid-activated, pathway.

The cyclin kinase inhibitor p21 is acutely upregulated during acute kidney injury (AKI) and exerts cytoprotective effects. A proposed mechanism is oxidant stress-induced activation of p53, the dominant p21 transcription factor. Glycerol-induced rhabdomyolysis induces profound renal oxidant stress. Hence, we studied this AKI model to determine whether p53 activation corresponds with p21 gene induction and/or whether alternative mechanism(s) might be involved. CD-1 mice were subjected to glycerol-induced AKI. After 4 or 18 h, plasma, urinary, and renal cortical p21 protein and mRNA levels were assessed. Renal p53 activation was gauged by measurement of both total and activated (Ser15-phosphorylated) p53 and p53 mRNA levels. Glycerol evoked acute, progressive increases in renal cortical p21 mRNA and protein levels. Corresponding plasma (~25-fold) and urinary (~75-fold) p21 elevations were also observed. Renal cortical ratio of total to phosphorylated (Ser15) p53 rose three- to fourfold. However, the p53 inhibitor pifithrin-α failed to block glycerol-induced p21 gene induction, suggesting that an alternative p21 activator might also be at play. To this end, it was established that glycerol-induced AKI 1) dramatically increased plasma (~5-fold) and urinary (~75-fold) cortisol levels, 2) the glucocorticoid receptor antagonist mifepristone blocked glycerol-induced p21 mRNA and protein accumulation, and 3) dexamethasone or cortisol injections markedly increased p21 protein and mRNA in both normal and glycerol-treated mice, although no discernible p53 protein or mRNA increases were observed. We conclude that AKI-induced "systemic stress" markedly increases plasma and urinary cortisol, which can then activate renal p21 gene expression, at least in part, via a glucocorticoid receptor-dependent signaling pathway. Discernible renal cortical p53 increases are not required for this dexamethasone-mediated p21 response.

A clinical and radiological study of nontraumatic coccygodynia in Indian population

Background: Nontraumatic coccygodynia is poorly understood. Dynamic radiographs help to identify a radiological lesion. This study was performed to evaluate these parameters and define a line of management. Materials and Methods: A total of 46 cases with nontraumatic coccygodynia and 46 controls who met the inclusion criteria were evaluated using dynamic radiographs between June 2015 and May 2017. Radiological parameters, such as sagittal movement of coccyx, intercoccygeal angle (ICA), base angle (BA), and angle of pelvic rotation (APR), were calculated and compared between cases and controls to identify the radiological lesion in cases. On the basis of clinico-radiological findings, a treatment algorithm for these patients was proposed. Results: A total of 46 cases and 46 controls were studied. The mean age was 41.8 years in cases and 40.6 years in controls. Body mass index (BMI) ranged from 19 to 33. Twenty-nine cases had BMI >25. Average visual analog scale score at initial presentation (6.9), at 6 weeks (4.7), and final follow-up (3.9) was noted. ICA ranged from 1° to 21° (mean 11.12°). BA ranged from 0° to 83° (mean 41.41°). APR ranged from 2° to 33° (mean 14.74°). Twenty-seven patients had a good relief with local hydrocortisone injection and manipulation, whereas nine cases needed coccygectomy. Conclusion: Dynamic radiographs help in defining the radiological parameters and planning treatment. The sagittal movement of extension, posterior subluxation, higher BA, and low APR are the radiological findings seen in patients of nontraumatic coccygodynia. Majority of patients respond to conservative management; however, few may need surgical intervention.

The knowledge of and attitudes toward anaphylaxis emergency management among Polish dentists

INTRODUCTION: Anaphylaxis is a life-threatening medical emergency condition requiring immediate diag- nosis and implementation of proper treatment. For the medical personnel facing a patient suspected of anaphylaxis, the necessary rapid initial management includes removing the allergen, calling for help, clear- ing the airway, laying the patient, and administering adrenaline in an intramuscular injection and oxygen. Airway management, intravenous access, and intravenous fluid challenge, as well as chlorphenamine and hydrocortisone injection, are also suggested if the medical personnel has appropriate skills and equipment available. Many studies emphasize that dentists feel inadequately trained to recognize and treat medical emergencies in dental offices, which especially refers to anaphylaxis. The aim of the study was to assess the dentists’ preparedness, knowledge, and attitudes with regard to anaphylaxis in dental offices in Poland. METHODS: The study was conducted between November 2016 and November 2017 during scientific meet- ings and congresses in Poland. The participants (Polish dentists) received information on the study objectives and voluntarily took part in the questionnaire survey. The questionnaire included 20 items concerning age, gender, work experience, specialization, latest training in cardiopulmonary resuscitation, onset time of aller- gic reaction, stridor, first line pharmacological treatment, route of administration and doses of adrenaline in different age groups, other medications recommended in anaphylaxis. RESULTS: Overall, 500 active dentists working in Poland were offered to participate in the questionnaire study; 268 questionnaires were returned (53.6%), including 18 partially filled. Finally, 250 questionnaires were further analyzed. The mean age of the participants was 42.33 ± 10.53 years, 226 (90.4%) were fe- male, and the mean work experience equaled 14.35 ± 9.27 years. The total of 28.8% of subjects attended cardiopulmonary resuscitation training within 12 months prior to the study, 38.40% within the previous 2–5 years, 17.20% within the previous 6–10 years, 8.00% 10 or more years earlier, and 7.60% had never participated in such training since graduation. 24.4% of the participants stated that ingestion of food to which a patient was allergic resulted in severe anaphylactic reaction typically within 30 minutes, and 21.60% stated that in the case of contact with bee or wasp venom, severe anaphylaxis typically occurred within 10–15 minutes. Out of the study participants, 66.40% maintained that adrenaline was the first line drug in anaphylaxis; 27.2% indicated intramuscular route as the standard route for adrenaline injection in anaphylaxis; 46.4% pointed at the correct dose of adrenaline in anaphylaxis. The proper adrenaline dose in anaphylaxis for a 4-year-old child was indicated by 42.00% and for a 10-year-old child by 36.4%. The correct dose of hydrocortisone in a 10-year-old child was provided by 18.40%. CONCLUSIONS: Among Polish dentists, the knowledge concerning the diagnosis and emergency treatment in anaphylaxis is low. Better postgraduate training including anaphylaxis management in dental offices should be recommended.

Effects of glucocorticoid on the eye development in guinea pigs

Glucocorticoid (GC) has been widely used in clinic. However, the effect of GC on normal and myopic development of eyes is still unknown. In this study, 3-week-old guinea pigs were randomly divided into four groups: No-Lens (control), GC+No-Lens, negative lens-induced myopia (LIM), and GC+LIM. To induce myopia, right eyes were covered with a −10 D lens in GC+LIM and LIM groups. GC+No-Lens and GC+LIM groups received intraperitoneal injections of hydrocortisone (10 mg/kg) once daily for 2 weeks, and then received intragastric hydrocortisone (32.5 mg/kg) every other day for the next 4 weeks, while No-Lens (control) and LIM groups were injected intraperitoneally with saline for 2 weeks, and then given saline by intragastric administertion for the next 4 weeks. Several parameters were assessed: ocular axial length and refractive error, sclera thickness, matrix metalloprotein-2 (MMP-2) and tissue inhibitor metalloprotease-2 (TIMP-2) expressions and localization of the posterior sclera, plasma concentrations of free triiodothyronine (FT3), free thyroxine (FT4), testosterone (T), and oestradiol (E2). Results indicated that: (1) in normal eye development, hydrocortisone could inhibit both the axial elongation and the myopic shift; whereas (2) in LIM eye development, hydrocortisone (a) enhanced the axial elongation, myopic shift and sclera thinning; (b) enhanced the MMP-2 expression and decreased TIMP-2 expression, and (c) elevated the plasma concentration of E2 but decreased the levels of FT3, FT4, and T. In conclusion, glucocorticoid may influence both normal and LIM eye development. The balance of the hormones is fundamental for the eye development.

Glucocorticoid susceptibility and in vivo ABCB1 activity differ in murine B cell subsets.

Glucocorticoids are produced and released by the adrenal gland and become elevated in response to stress. Although glucocorticoids are well known for their immunosuppressive effects, less is known about their effects on B cells. ABCB1 is an efflux pump expressed in both cancer and normal cells, modulating the gradient of various metabolites, including hydrocortisone. Our goal was to evaluate the effect of this glucocorticoid on murine B cell differentiation and whether sensitivity to hydrocortisone could be related to ABCB1 activity in vivo. C57BL/6 mice received one or three consecutive i.p. injections of hydrocortisone (70, 140 and 200 mg/kg/day). ABCB1 activity was evaluated via the rhodamine-123 transport and inhibited by cyclosporin A in hydrocortisone-treated and control mice. Cells from bone marrow, spleen and blood were counted, incubated with antibodies and analyzed by flow cytometry. A single hydrocortisone injection did not alter the number of bone marrow subsets. Conversely, three daily injections were able to reduce the cell number of most bone marrow subsets, excepting c-kit-sca-1+ and mature B cells. This treatment reduced marginal zone, follicular and transitional B cells, though splenic subsets were more resistant than bone marrow B cells. Recirculating follicular B cells in the blood were resistant to hydrocortisone. With the exception of follicular B cells, all subpopulations exhibited ABCB1 activity. However, hydrocortisone treatment did not affect ABCB1 activity in most subsets analyzed. Results suggest that hydrocortisone is able to regulate B cell lymphopoiesis although ABCB1 activity is not related to the susceptibility to that glucocorticoid in B cell subsets.

Radiolabel validation of cortisol in the hair of rhesus monkeys

Analysis of cortisol in hair has become a widespread tool for assessment of hypothalamic-pituitary-adrenal (HPA) axis activity because of its ease of collection and its ability to provide cumulative data over a period of months. In order to meaningfully interpret hair cortisol, however a direct validation by radio-metabolism is required to understand cortisol incorporation into hair. Tritiated [3H]-cortisol was IV administered to adult rhesus monkeys to determine 1) if [3H] is found in the hair after injection of [3H]-cortisol, 2) the growth rate of hair and 3) the form in which cortisol is found in hair. Samples of hair were collected from newly and previously shaved patches at 14-days and 28-days after [3H]-cortisol injection. Hair was processed by external wash, grinding, and hormone extractions. Samples were separated by high-performance liquid chromatography (HPLC) and fractions were collected and radioactivity assessed. We found [3H] incorporated into the hair by the 14-day hair collection and no new radioactivity was found by the 28-day collection. Individual hair growth rate was highly variable between monkeys, indicating that the between-subject hair growth patterns were not consistent. Importantly, for the first time, we showed that systemically administered [3H]-cortisol was found in the hair as [3H]-cortisol and [3H]-cortisone, as well as other glucocorticoid metabolites.