Use Of High Doses Research Articles

Individualization of FSH Doses in Assisted Reproduction: Facts and Fiction.

The art of ovarian stimulation for IVF/ICSI treatment using exogenous FSH should be balanced against the relative contribution of other steps of the ART process such as the IVF-lab-phase and the Embryo-Transfer. The aim of ovarian stimulation is to obtain a certain number of oocytes, that will enable the best probability of achieving a live birth. It has been suggested that more oocytes will create a better prospect for pregnancy, but studies on the question whether the retrieval of a few oocytes less or more will make the difference are not clearly supportive for this mantra. Personalization strategies have been the subject of many studies over the past 20 years. Creating the optimal response in a patient in terms of live birth prognosis as well as OHSS risks may be based on information from the Ovarian Reserve testing using the Antral Follicle Count or Anti-Mullerian Hormone, the patient's bodyweight, the ovarian response in a previous cycle, and the dosage level of FSH. Taken together, steering the ovarian response into a supposed optimal range may appear difficult as the interrelation for each of these factors with the egg number is weak. Using OR testing for choosing FSH dosage, compared to a standard normal dosage of 150 IU, has been studied in several trials. Dosage individualization, in general, does not appear to improve the prospects for live birth, but the reduction in OHSS risk may be substantial. This implies that the use of high dosages of FSH in predicted LOW responders lacks any cost-benefit for the patient and may be abandoned, while in predicted HIGH responders, reduction of the usual dosage level of 150 IU may create better safety, provided that in case of an unexpected LOW response cancelation of the cycle is refrained from. In view of recent developments in using GnRH agonist triggering of final oocyte maturation, the trend could be that with the Antagonist co-medication system and a standard dosage of 150 IU of FSH, prior ovarian reserve testing may become futile, as safety can be managed well in actual HIGH responders by replacing the high dose hCG trigger.

Clinical model of hyaluronic acid embolism treated with hyaluronidase and its effects on the arterial wall and adjacent tissues

IntroductionHyaluronic acid (HA) is a glycosaminoglycan used cross‐linked to increase its durability and be used as a temporary facial filler. One of the most striking complications of its use is vascular occlusion, causing permanent lesions and scars. The use of hyaluronidase (HYAL) was evaluated subcutaneously (SC) and intra‐arterially (IA) in a lagomorph model causing an HA embolism in the ear, however, the model has few similarities to the clinical application site. In addition, different doses of HYAL have been evaluated, but they have not been compared to each other, nor has the safety of adjacent tissues been evaluated. Our aim was to determine an effective and safe concentration of HYAL applied extravascularly to dissolve an HA embolism.Materials and methodsWe used 15 New Zealand rabbits divided into 6 groups (Healthy, Surgical, Embolism, 75UI, 200UI, and 500UI). An HA (Belotero Balance®) embolism was performed in the left femoral artery to the embolism control group and to the three embolism groups treated with HYAL SC 1 hour after the embolism. Samples were taken in block obtaining artery, vein, nerve, muscle, and skin on the 5th day. Histologic staining and histochemistry was performed. Quantification of HA (Image J®) was performed, and morphological changes in the artery and adjacent tissues were analyzed. Study was approved by the Care and Use of Laboratory Animals and Ethics Committees.ResultsDespite the persistence of HA in the arterial lumen of the treated groups, a significant difference was found between the 200UI (p = 0.002) and 500UI (p = 0.001) groups of HYAL and the embolism control group. Sites of arterial thrombosis were observed in the embolism groups and those treated with HYAL. When evaluating the surrounding tissues, the muscle of the group treated with high dose had less muscle lysis and less inflammatory infiltrate.ConclusionA new lagomorph model of embolism due to HA was established with greater similarity to the site of clinical application than those already established. A high dose of HYAL, applied subcutaneously, partially prevents the damage caused by the embolism. The use of thrombolytic therapy combined with the use of higher doses of HYAL SC in this model is proposed.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sustained, delayed, and small increments in glomerular permeability to macromolecules during systemic ET-1 infusion mediated via the ETA receptor.

Emerging evidence indicates that endogenous production of endothelin (ET)-1, a 21-amino acid peptide vasoconstrictor, plays an important role in proteinuric kidney disease. Previous studies in rats have shown that chronic administration of ET-1 leads to increased glomerular albumin leakage. The underlying mechanisms are, however, currently not known. Here, we used size-exclusion chromatography to measure glomerular sieving coefficients for neutral FITC-Ficoll (molecular Stokes-Einstein radius: 15-80 Å, molecular weight: 70 kDa/400 kDa) in anesthetized male Sprague-Dawley rats (n = 12) at baseline and at 5, 15, 30, and 60 min after intravenous administration of ET-1. In separate experiments, ET-1 was given together with the selective ET type A (ETA) or ET type B (ETB) receptor antagonists JKC-301 and BQ-788, respectively. At both 15 and 30 min postadministration, the glomerular sieving coefficient for macromolecular Ficoll (70 Å) was significantly increased to 4.4 × 10-5 ± 0.7 × 10-5 (P = 0.024) and 4.5 × 10-5 ± 0.8 × 10-5 (P = 0.007), respectively, compared with baseline (2.2 × 10-5 ± 0.4 ×10-5). Decreased urine production after ET-1 prevented the use of higher doses of ET-1. Data analysis using the two-pore model indicated changes in large-pore permeability after ET-1, with no changes in the small-pore pathway. Administration of ETA blocker abrogated the permeability changes induced by ET-1 at 30 min, whereas blockade of ETB receptors was ineffective. Mean arterial pressure was only significantly increased at 60 min, being 123 ± 4 mmHg compared with 111 ± 2 mmHg at baseline (P = 0.02). We conclude that ET-1 evoked small, delayed, and sustained increases in glomerular permeability, mediated via the ETA receptor.

Combination of 5-Florouracil and polyphenol EGCG exerts suppressive effects on oral cancer cells exposed to radiation

ObjectiveNatural compounds such as epigallocatechin-3-gallate (EGCG) have previously shown chemotherapeutic properties with few side-effects. In our study, we evaluated the effects of combining EGCG with 5-fluorouracil (5-FU) and radiotherapy on oral squamous cell cancer. We evaluated whether the combination of lower doses of 5-FU with EGCG could be equally or more effective than the use of higher doses of 5-FU alone. MethodsCell viability, migration and cell cycles were assayed in oral cancer cell lines treated with 5-FU, 5-FU + EGCG and radiation (0, 2.5 and 5 Gy). ResultsThis study found that the combination of EGCG with 5-FU reduced cell viability and migration distance compared to control samples and the same dose of 5-FU alone. Addition of EGCG increased the number of cells in the G2/M phase, while 5-FU arrested the cell cycle in phase S. Moreover, cell exposure to 5 Gy radiation decreased the effects of combining with EGCG. ConclusionsIn summary, the combination of EGCG and 5-FU reduced both cell viability and migration as well as altered the cell cycle to a greater extent than 5-FU alone.

P095 COMPARING ORAL CORTICOSTEROIDS ≥30MG/DAY AMONG ADULT AND PEDIATRIC PATIENTS WITH NEWLY DIAGNOSED ULCERATIVE COLITIS

Ulcerative Colitis (UC) has a relapsing–remitting disease course. Sparing use of oral corticosteroids (CS) ≥30 mg/day, as mono or combination therapy, are generally reserved for rapid relief of symptoms and induction of remission to achieve optimal therapeutic response. This analysis aimed to compare patient profiles of adult and pediatric patients newly diagnosed with UC who use ≥30 mg/day CS in a real world setting. The Truven Marketscan commercial administrative claims database was used to explore the real-world utilization of ≥30mg/day CS among pediatric (children 2- 11 years old and adolescents 12-17 years old) and adult (≥18 years old) UC patients. Patients were identified based on first diagnosis of UC during 01/01/2013 -12/31/2015 and were included in the analysis if they had an additional UC diagnosis during the 1-year post-index period. Patients with pre-specified, common inflammatory comorbid conditions associated with high doses of oral CS were excluded. The final sample was subsequently stratified based on number of days (d) [0, 1-7, 8-30, 31-90, 91-180, 181-365] on ≥30mg/day oral CS during follow-up (1-year post diagnosis). Pre-index and post-index patient characteristics (demographics, medications, and health care resource use (HCRU)) are described. A total of 10,443 UC patients were included in this analysis consisting of 91 children (2-11 years old), 290 adolescents (12-17 years old), and 10,062 adults (18+ years old). Demographic information such as age, gender, and geographic location for each subgroup is displayed in Table 1. Approximately, 40.66% of children and 46.90% of adolescents received corticosteroids during the 1-year post-index period, compared to only 14.62% of adults. In addition, 25.27% of children, 34.48% of adolescents, and 6.68% of adults received corticosteroids for more than 30 days during the post-index period. Among all subgroups, patients with ≥30d of ≥30mg/day CS use were more likely to be prescribed biologics. HCRU (including gastroenterologist visits, ER visits, and inpatient visits) was higher for patients receiving ≥30mg/day of CS at least 1 day during the post-index period when compared to those not receiving ≥30mg/day of CS. HCRU was higher among the pediatric subgroups (children and adolescents) when compared to adults (Table 1). During a 1-year follow-up period, UC patients with a longer duration of ≥30mg/day CS use were more likely to be on a biologic and had increased HCRU. This analysis of real-world data suggests that there is a subset of newly diagnosed pediatric and adult patients with UC who may require longer use of higher doses of oral CS to achieve optimal therapeutic response. This analysis also suggests that pediatric UC patients are more likely to be treated with corticosteroids and have higher HCRU when compared to the adult UC population.

P095 COMPARING ORAL CORTICOSTEROIDS ≥30MG/DAY AMONG ADULT AND PEDIATRIC PATIENTS WITH NEWLY DIAGNOSED ULCERATIVE COLITIS

Ulcerative Colitis (UC) has a relapsing–remitting disease course. Sparing use of oral corticosteroids (CS) ≥30 mg/day, as mono or combination therapy, are generally reserved for rapid relief of symptoms and induction of remission to achieve optimal therapeutic response. This analysis aimed to compare patient profiles of adult and pediatric patients newly diagnosed with UC who use ≥30 mg/day CS in a real world setting. The Truven Marketscan commercial administrative claims database was used to explore the real-world utilization of ≥30mg/day CS among pediatric (children 2- 11 years old and adolescents 12-17 years old) and adult (≥18 years old) UC patients. Patients were identified based on first diagnosis of UC during 01/01/2013 -12/31/2015 and were included in the analysis if they had an additional UC diagnosis during the 1-year post-index period. Patients with pre-specified, common inflammatory comorbid conditions associated with high doses of oral CS were excluded. The final sample was subsequently stratified based on number of days (d) [0, 1-7, 8-30, 31-90, 91-180, 181-365] on ≥30mg/day oral CS during follow-up (1-year post diagnosis). Pre-index and post-index patient characteristics (demographics, medications, and health care resource use (HCRU)) are described. A total of 10,443 UC patients were included in this analysis consisting of 91 children (2-11 years old), 290 adolescents (12-17 years old), and 10,062 adults (18+ years old). Demographic information such as age, gender, and geographic location for each subgroup is displayed in Table 1. Approximately, 40.66% of children and 46.90% of adolescents received corticosteroids during the 1-year post-index period, compared to only 14.62% of adults. In addition, 25.27% of children, 34.48% of adolescents, and 6.68% of adults received corticosteroids for more than 30 days during the post-index period. Among all subgroups, patients with ≥30d of ≥30mg/day CS use were more likely to be prescribed biologics. HCRU (including gastroenterologist visits, ER visits, and inpatient visits) was higher for patients receiving ≥30mg/day of CS at least 1 day during the post-index period when compared to those not receiving ≥30mg/day of CS. HCRU was higher among the pediatric subgroups (children and adolescents) when compared to adults (Table 1). During a 1-year follow-up period, UC patients with a longer duration of ≥30mg/day CS use were more likely to be on a biologic and had increased HCRU. This analysis of real-world data suggests that there is a subset of newly diagnosed pediatric and adult patients with UC who may require longer use of higher doses of oral CS to achieve optimal therapeutic response. This analysis also suggests that pediatric UC patients are more likely to be treated with corticosteroids and have higher HCRU when compared to the adult UC population.

Relationship between mirtazapine dose and incidence of adrenergic side effects: An exploratory analysis.

IntroductionMirtazapine is an antidepressant with US Food and Drug Administration approval for management of major depressive disorder. Low doses of mirtazapine are often used for management of insomnia, with higher doses expected to provide more noradrenergic effect, and thus a higher degree of activation. If so, use of higher doses at bedtime may not be advisable and may worsen certain neuropsychiatric symptoms. No studies have been performed to evaluate these outcomes.MethodsThis study consisted of a retrospective review of data submitted to the US Food and Drug Administration's Adverse Event Reporting System from January 1, 1995, to August 1, 2015. Cases that were deemed by study authors to represent activation of the noradrenergic system, and for which other confounders could not be identified, were included in the final analysis. The frequency of each specific adverse event was evaluated based on dose and compared to recent prescribing rates to determine if likelihood of a side effect increased with higher dose.ResultsThe study identified 308 incidences of anxiety, agitation, delusion, hallucination, hypertension, insomnia, nightmare, or tachycardia. After controlling for frequency of prescribing at a given dose, there was a statistically significant increase in rates of tachycardia which correlated with dose. However, after correction for multiple comparisons, results were no longer significant.DiscussionThis study failed to support the hypothesis that mirtazapine is more activating at higher doses and appears to support the safety of increasing dose without increasing risk of noradrenergic side effects. Prospective studies will be necessary to confirm these findings.

Resistance Mapping of the Genus Cyperus in Rio Grande do Sul and Selection Pressure Analysis

ABSTRACT: Among the species of the genus Cyperus occurring in paddy rice, C. esculentus, C. difformis and C. iria are the most important, and the latter two are reported as resistant to herbicides in Rio Grande do Sul (RS). The aim of this work was to characterize and mapping the occurrence of resistant plants of the genus Cyperus in areas of paddy rice in RS State, and to analyze the agronomic factors that interfere in the resistance selection. Seeds from individual plants were harvested in the 2014/15 crop, characterized as control failures by the application of acetolactate synthase inhibitors (ALS), totaling 43 samples. At the time of collection, the grower was inquired on aspects related to the management of weeds in the crop. Seeds were germinated in BOD and when seedlings were in two leaves stage they were transplanted into 0.3 L pots containing substrate. When the plants had 4-6 leaves, imazapyr + imazapic was spray at the registration rate. Thirty days after application, control of the tested biotypes was evaluated, converting the data to binary scale, where zero (0) and one (1) correspond to susceptibility and resistance, respectively. The agronomic factors that denote the high selection pressure of resistant biotypes are the consecutive use of Clearfield® technology, the use of higher doses than the registration and the low crop rotation adoption. Although not mentioned as one of the main weeds, it is observed that almost half of the samples collected from plants of the genus Cyperus are resistant to the ALS inhibitors, distributed in almost all the growing regions.

Evaluation of the safety of oral intake of aqueous extract of Stigma maydis (corn silk) in rats.

Corn silk (Stigma madyis) is used in ethnomedicine for the management of diabetes, kidney stones, depression, fatigue, urinary infections and as a slimming tea. However, there is limited literature on its effect on body weight, lipid, hematological, hepatocellular, nephrological and histopathological indices which the present study evaluated. In the acute toxicity test, aqueous extract of Stigma madyis was orally adminis- tered to rats using a gavage, in doses of up to 5 g/kg body weight. The rats were observed for any behavioral changes, signs of toxicity or mortality. In the sub-acute toxicity, rats were orally administered 500, 1000 and 2000 mg/kg Stigma madyis extract for 28 days. On the 29th day, the rats were euthanized and the following parameters measured; lipid profile, hematology, serum chemistry and histopathology of the liver and kidney. In the acute toxicity test, Stigma madyis did not cause any mortality and was non-toxic at the dose of up to 5 g/kg body weight. In the sub-acute study,&nbsp; the extract caused an observable significant increase&nbsp;&nbsp; (p < 0.05) in triglycerides (TAG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL), while the concentration of high density lipoprotein (HDL) decreased significantly (p < 0.05) when compared to the control group. AST and ALT increased significantly (p < 0.05) in rats treated with 1000 and 2000 mg/kg of Stigma maydis compared to their control. The histopathological results revealed degenerative changes in the liver at 2000 mg/kg body weight extract. In long term treatment, toxic effects were observed in liver at the doses of 1000 and 2000 mg/kg. This study suggests that prolonged use of higher doses of aqueous extract of Stigma maydis &ge; 1000 mg/kg could be hepatotoxic. Therefore, only lower doses should be encouraged for therapeutic use.

Ethanolic leaf extract of Ipomoea aquatica Forsk abrogates cisplatin-induced kidney damage in albino rats

Introduction: The efficacy of cisplatin (CPT) is dose dependent, but the risk of nephrotoxicity hinders the use of higher doses to maximize its antineoplastic effect. Ipomoea aquatica Forsk (IA) is a medicinal plant used in folklore for the treatment of many ailments. Objectives: This study assessed the protective effect of the ethanolic leaf extract of I. aquatica (EEIA) against a rat model of CPT-induced kidney damage. Materials and Methods: Fifty-four adult albino rats used for this study were randomized into 9 groups of 6 rats each. Rats were orally pretreated with 100, 200 and 400 mg/kg of EEIA daily for 7 days and were administered with 6 mg/kg of CPT intraperitoneally (ip) on the fifth and seventh day. On the eighth day, rats were sacrificed, blood was collected, and kidneys were excised. Plasma was extracted from blood and evaluated for renal function indices while kidneys were evaluated for oxidative stress markers and histology. Results: The effects of CPT on the body and kidney weights were not significant (P>0.05) when compared to control. However, CPT-induced kidney damage showed significant (P<0.05) increases in creatinine, urea, uric acid, and malondialdehyde levels when compared to control. Furthermore, significant (P<0.05) decreases in superoxide dismutase, catalase, glutathione, glutathione peroxidase, total protein, albumin, sodium, chloride, potassium and bicarbonate levels were obtained in CPT-treated rats when compared to control. The kidneys of CPTtreated rats were marked by extensive tubular necrosis. However, CPT-induced nephrotoxic effects were significantly (P<0.01; 0.05) and in a dose- dependent manner reversed in EEIA pretreated rats. Conclusion: The ethanolic leaf extract of I. aquatica Forsk contains essential constituents that can be used to treat CPT associated kidney injury.

Immunomodulatory Effects of Tigecycline in Balb/C Mice.

Tigecycline is a glycylcycline antibiotic approved by the FDA for the treatment of complicated infections. Despite its effectiveness, the FDA announced a warning of increasing mortality associated with its use. There is, however, no clear explanation for this side effect. Previous reports found a possible effect of tigecycline on leukocyte proliferation and proinflammatory cytokine release. We t herefore i nvestigated the effect of tigecycline on the immune components and response in Balb/c mice in vivo and in vitro. It was found that tigecycline enhanced lymphocyte proliferation and significantly increased cellular infiltration within the footpad, as based on DTH testing, but reduced the hemagglutination titer. In splenocyte cultures, tigecycline suppressed splenocyte proliferation with IC50 3-5 mmol L-1, significantly increased IL-2 secretion and reduced IL-17 secretion in a dose dependent mode. In conclusion, tigecycline is safe at therapeutic and sub-therapeutic doses, but it could still have an immunomodulatory effect at higher doses. Use of higher doses of tigecycline requires further investigation.

Dual layered wound dressing with simultaneous temperature & antibacterial regulation properties

Scald first-aid needs to reduce the local temperature as well as the bacterial colonization. Bacteria resistant problem has become a major challenge that global public health workers face. Long-term and high dosage use of antibacterial agents is the main reason. In this study, temperature-regulated release antibacterial nanoparticles were applied to poly(n-isopropyl acrylamide) and sodium polyacrylate. This hypothermia coverage could be used as an ideal scald first-aid wound dressing with spontaneous Temperature & Antibacterial regulation properties.

Chemical and pharmacological aspects of neutralization of heparins from different animal sources by protamine

Background Protamine neutralization is an essential step for the safe use and inactivation of the unfractionated heparin (UFH) that is widely employed in surgical and non-surgical procedures involving extracorporeal circulation. Objective To compare protamine neutralization of different pharmaceutical-grade UFHs prepared from porcine or bovine intestine (HPI and HBI, respectively). HBI has approximately half the anticoagulant potency of HPI, mostly as consequence of its fraction enriched with N-sulfated α-glucosamine disaccharides. Methods Protamine neutralization of HPI and HBI was evaluated with invitro, exvivo and invivo assays. We also performed in-depth assessments of the complexation of protamine with these distinct UFHs by using nuclear magnetic resonance and mass spectroscopy. Results HPI and HBI interact similarly with protamine on a mass/mass basis; however, HBI requires more protamine than HPI to have its anticoagulant activity fully neutralized, because of its lower potency, which entails the use of higher doses. Nuclear magnetic resonance spectra revealed that HPI precipitates homogeneously with protamine. On the other hand, the low-sulfated fraction of HBI, enriched with N-sulfated α-glucosamine, precipitates at higher concentrations of protamine than the fraction more like HPI, with a preponderance of N,6-disulfated α-glucosamine disaccharides. Finally, mass spectroscopy spectra showed that some of the different peptide components of protamine interact preferentially with the heparins, irrespective of their animal origin. Conclusion Our results have important medical implications, indicating that protamine neutralization of HBI, determined exclusively by point-of-care coagulation assessments, must fail because of its lower-sulfated fraction with reduced anticoagulant activity that could remain in the circulation after the neutralization procedure.

Association of Anemia and Iron Parameters With Mortality Among Patients Undergoing Prevalent Hemodialysis in Taiwan: The AIM - HD Study.

BackgroundThe Taiwan Health Insurance Bureau has conducted a bundled payment system for hemodialysis reimbursement since 1995. The maximum dose of erythropoiesis‐stimulating agents allowed by insurance is capped at 20 000 U of epoetin or 100 μg of darbepoetin alfa per month. Nephrologists have avoided the use of high dosages of erythropoiesis‐stimulating agents to achieve a hemoglobin level of 10 to 11 g/dL by iron supplementation. The clinical impact of these policies on patients’ outcomes is unknown. The authors aimed to assess the AIM‐HD (Association of Anemia, Iron parameters, and Mortality among the prevalent Hemodialysis patients) Study in Taiwan.Methods and ResultsThe AIM‐HD study was conducted based on the Taiwan Renal Registry Data System. From 2001 to 2008, the authors enrolled 42 230 patients undergoing hemodialysis who were older than 20 years and had received hemodialysis for more than 12 months. Patient follow‐ups occurred until death or December 31, 2008. During a study period of 8 years, 12 653 (30.0%) patients died. After multivariate adjustment, the authors found that a hemoglobin level <10 g/dL was significantly associated with higher risk for all‐cause and cardiovascular deaths. Moreover, a serum ferritin level between 300 and 800 ng/mL and transferrin saturation value between 30% and 50% were associated with the lowest all‐cause mortality.ConclusionsThe authors recommend avoiding a low hemoglobin level and maintaining serum ferritin between 300 and 800 ng/mL and transferrin saturation between 30% and 50%, which were associated with lower risks of all‐cause mortality among patients undergoing hemodialysis receiving the restricted erythropoiesis‐stimulating agent doses but prompt intravenous iron supplementation in Taiwan.

Response of tomato (Lycopersicon esculentum Mill.) growth to different phosphorous levels and sowing dates

A field trail was carried out at the University of Agriculture Peshawar during spring, 2013 in order to evaluate the effect of different levels of phosphorus fertilizer and various planting times on the growth and development of tomato. The main objective of the research work was to investigate the best sowing time for tomato in combination with suitable dose of P fertilizer in order to get maximum yield of tomato in the climatic conditions of Peshawar. RCB Design with split plot arrangements was used in the trail. The main factor (phosphorous levels of 0, 90, 110, 130) was allotted to main plots while sowing dates in sub plots. A total twelve treatment were replicated thrice. Maximum days to flowering (39.583 days) and fruiting (46.167 days) obtained in the late sowing. Minimum days to flowering (39), minimum days to fruiting (38.778 days) were taken by the early sowing. Maximum number of branches (27.778), maximum fruit length (6.0222), maximum fruit with (6.1667), maximum fruit yield (24.653 tons ha−1) was produced when the plot fertilize with 130 kg P ha−1. Maximum number of fruit plant−1 (29.778) were produced with application of 130 kg P ha−1, minimum number of fruits (23.667 cm), fruit width (3.778 cm), fruit length (4.3667 cm), plant height (56.300 cm) were obtained from the controlled treatment. Among the various treatment studied in experiment, it is concluded that early planting of the tomato in the summer season i.e. in the start of March and the use of higher dose of P (130 kg P ha−1) is very beneficial for the excellent growth, development and yield of tomato crop.

Effect of Insulin-Induced Lipodystrophy on Glycemic Control among Children and Adolescents with Diabetes in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

Background Lipodystrophy is one of the clinical complications of insulin injection that affects insulin absorption and leads to poor glycemic control. Objective To assess insulin-induced lipodystrophy and glycemic control. Methods A cross sectional study was done on 176 diabetic children and adolescents who inject insulin for a minimum of one year. First, anthropometric and clinical characteristics of the patients were recorded in questionnaire, and then observation and palpation techniques were used in assessing lipodystrophy. Result Out of the total 176 participants, 103 (58.5%) had insulin-induced lipodystrophy, of them 100 (97.1%) had lipohypertrophy and 3 (2.9%) had lipoatrophy. Being younger, failure to rotate the injection site every week and multiple reuse of insulin syringe had significant influence in development of insulin-induced lipohypertrophy. Lipohypertrophy in turn was associated with the use of higher dose of insulin and nonoptimal glycemic control. Conclusion Findings of this study revealed that in spite of using recombinant human insulin, the magnitude of the lipohypertrophy still remained high. Therefore, a routine workup of insulin-injecting patients for such complication is necessary, especially in the individuals who have a nonoptimal glycemic control.

Successful off-label sulfonylurea treatment of neonatal diabetes mellitus due to chromosome 6 abnormalities

Chromosome 6 abnormalities such as paternal uniparental isodisomy, paternal 6q24 duplication, and maternal DMR (differentially methylated region) hypomethylation are a common cause of transient neonatal diabetes mellitus (TNDM). Oral sulfonylurea (SU) is used off-label to treat permanent neonatal diabetes mellitus owing to potassium channel mutation but has not been evaluated in TNDM. Our objective was to evaluate the efficacy and safety of SU therapy in chromosome 6-related TNDM. Description of 3 case reports and literature review was the subject of the study. SU therapy was successful in 2 patients (initiated during neonatal life in 1 patient and during relapse in the other) but failed in the other despite the use of high dosage. The literature review identified 11 cases of patients with chromosome 6-related TNDM treated with SU, including 4 treated before remission and 7 after the relapse. SU therapy was consistently effective, although 4 patients treated after the relapse required multiple oral medications. None of the patients needed associated insulin therapy. No side effects of SU or complications of diabetes were reported. SU seems effective and safe in chromosome 6-related TNDM treatment when used to treat the initial episode of diabetes or the relapse. It improves patients' and families' quality of life. SU is available only as oral tablets. A pediatric dosage form would facilitate the treatment of neonates and infants.

Clinical experience with ceftolozane/tazobactam in patients with serious infections due to resistant Pseudomonas aeruginosa.

The incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) has become a concern of increasing relevance nowadays. Ceftolozane/tazobactam (C/T) is a novel fifth-generation cephalosporin/β-lactamase inhibitor combination with activity against MDR-Pa. The clinical records of all patients diagnosed from May 2016 to May 2017 with an infection due to a MDR-Pa treated with C/T were retrospectively reviewed. A total of 23 patients with 24 episodes of infection due to MDR-Pa were included. The minimum inhibitory concentration (MIC) of C/T against MDR-Pa ranged from 0.75-8μg/mL. In 14 cases (58%) the use of C/T was off-label, including 8 respiratory tract infections (RTIs) and 6 skin and soft-tissue infections, whilst in 10 cases the use was for approved indications, including 7 urinary tract infections and 3 intra-abdominal infections. C/T was the first-line therapy in only three cases with a mean±standard deviation treatment duration of 9.3±4 days, and it was associated with another active drug (aminoglycoside or colistin) in 16 cases. The global clinical cure rate was 88% (21/24 episodes), and the 6-week mortality rate was 22% (5/23 patients) being higher in RTIs (37%). In these infections, three patients received 2/1g every 8h (q8h) and were cured without mortality, whilst three (60%) of five patients receiving 1/0.5g q8h died. C/T had good clinical responses in different types of infection, including both FDA-accepted and off-label indications. The results support the use of higher doses in RTIs.

Entomotoxic effect of silicon dioxide nanoparticles on Plutella xylostella (L.) (Lepidoptera: Plutellidae) under laboratory conditions

ABSTRACTThe use of higher dosage and repeated applications of conventional pesticides have led to the rapid development of insect resistance to pesticide and adverse effects on human health and environment. Accordingly, researchers are prompted to identify an alternative entomotoxic agent for crop protection. Nanocides are being considered as alternatives to conventional insecticides because they are expected to lessen the application rate and reduce the chances of resistance development in pests. In this study, we evaluated the entomotoxic effects of nanosilica on larvae of Plutella xylostella, in a laboratory by using dust spray, larva dipping, leaf dipping, and solution spray methods. Dust treatment showed a more highly significant effect than the other three treatments. The mortality percentage increased up to 58% and 85% at 24 and 72 h after treatment, respectively, when nanosilica was applied at a rate of 1 mg cm−2. In all four bioassays, mortality rate increased with both increased time after nanosilica exposure and increased concentration. Light microscopy and scanning electron microscopy images showed that larval death was due to desiccation, body wall abrasion, and spiracle blockage. These results suggested that nanosilica can be an alternative to conventional pesticides if dust formulation would be properly used.

Paradoxical Bactericidal Effects of Hydrophobic Lung Surfactant Proteins and Their Peptide Mimics Using Liposome Molecular Trojan.

Lung surfactant, besides alveolar stability, also provides defence against pathogens by surfactant proteins (SP), SP-A and SP-D. The hydrophobic proteins SP-B and SP-C enhance surface activity. An unusual and paradoxical effect of bovine LS and synthetic model LS with SP-B/-C was bactericidal to Staphylococcus aureus and Escherichia coli. Bacterial proliferation were investigated with bovine lung surfactant extract (BLES), dipalmitoylphosphatdylcholine, palmitooleylglycerol, in combination with SP-B/-C using standard microbiological colony forming unit (CFU) counts and structural imaging. BLES and other surfactant-SP-B/-C mixtures inhibit bacterial growth in the concentration range of 0 -7.5 mg/mL, at > 10 mg/mL paradoxical growth of both the bacterial species suggest antibiotic resistance. The lipid only LS have no effect on bacterial proliferation. Smaller peptide mimics of SP-B or SP-B1-25, were less efficient than SP-Cff. Ultra structural studies of the bacterial CFU using electron and atomic force microscopy suggest some membrane damage of S. aereus at inhibitory concentration of BLES, and some structural alteration of E. coli at dividing zones, suggesting utilization and incorporation of surfactant lipid species by both bacteria. The results depicted from in vitro studies are also in agreement with protein-protein interactions obtained from PatchDock, FireDock and ClasPro algorithm. The MD-simulation decipher a small range fluctuation of gyration radius of the LS proteins and their peptide mimics. The studies have alarming implications in the use of high dosages (100 mg/mL/kg body weight) of exogenous surfactant for treatment of respiratory distress syndrome, genetic knock-out abnormalities associated with these proteins, and the novel roles played by SP-B/C as bactericidal agents.