Enhanced Isolation of Streptomyces from Different Soil Habitats in Calamba City, Laguna, Philippines using a Modified Integrated Approach.

Streptomyces species are considered to be the most prolific sources of various bioactive secondary metabolites that are important for antibiotic production. Here, we describe a modified integrated approach to isolate Streptomyces species from diverse soil habitats, such as dumpsite, garden, forest, grassland, and riverside in Calamba City, Laguna, Philippines. A total of 25 soil samples were collected from a depth of 0-20 cm using systematic random soil sampling. All soil samples were air-dried, crushed, pretreated with calcium carbonate, and incubated on a rotary shaker. Isolation of Streptomyces in soil samples was then performed using the standard serial dilution plate technique on starch casein agar supplemented with nystatin (50 µg/ml) and ampicillin (5 µg/ml). Identification of the Streptomyces isolates was done using a polyphasic method that includes morphological and biochemical characterization. A total of 103 morphologically and biochemically distinct Streptomyces were isolated from diverse soil habitats. The number of Streptomyces isolates varied in each collection site, with the highest number collected from dumpsite soil and the least from forest soil. Most of the hydrogen sulfide producers were noted to be isolated from dumpsite samples. Moreover, more Streptomyces were isolated in soil habitats at higher altitudes with a slightly acidic to alkaline pH and a temperature ranging from 29 to 33°C. Employing the modified integrated approach, we have isolated up to 10 times more Streptomyces compared to early studies. These Streptomyces isolates can be valuable for future drug discovery and development research.

Randomized Trial of Motivational Interviewing to Prevent Early Childhood Caries in American Indian Children.

INTRODUCTION: In a randomized controlled trial, the effectiveness of motivational interviewing (MI) combined with enhanced community services (MI + ECS) was compared with ECS alone for reducing dental caries in American Indian children on the Pine Ridge Reservation. The intervention was developed and delivered with extensive tribal collaboration. METHODS: A total 579 mother-newborn dyads were enrolled and randomized to the MI + ECS and ECS groups. They were followed for 36 mo. Four MI sessions were provided, the first shortly after childbirth and then 6, 12, and 18 mo later. Both groups were exposed to ECS, which included public service announcements through billboards and tribal radio, as well as broad distribution of brochures on behavioral risk factors for early childhood caries (ECC), toothbrushes, and toothpaste. MI impact was measured as decayed, missing, and filled tooth surfaces (dmfs). Secondary outcomes included decayed surfaces, caries prevalence, and maternal oral health knowledge and behaviors. Modified intention-to-treat analyses were conducted. Eighty-eight percent of mothers completed at least 3 of 4 MI sessions offered. RESULTS: After 3 y, dmfs was not significantly different for the 2 groups (MI + ECS = 10, ECS = 10.38, P = 0.68). In both groups, prevalence of caries experience was 7% to 9% after 1 y, 35% to 36% at 2 y, and 55% to 56% at 3 y. Mean knowledge scores increased by 5.0, 5.3, and 5.9 percentage points at years 1, 2, and 3 in the MI + ECS group and by 1.9, 3.3, and 5.0 percentage points in the ECS group (P = 0.03), respectively. Mean maternal oral health behavior scores were not statistically significantly different between the treatment arms. CONCLUSION: In summary, the MI intervention appeared to improve maternal knowledge but had no effect on oral health behaviors or on the progression of ECC (ClinicalTrials.gov NCT01116726). KNOWLEDGE TRANSFER STATEMENT: The findings of this study suggest that motivational interviewing focusing on parental behaviors may not be as effective as previously hoped for slowing the development of childhood caries in some high-risk groups. Furthermore, social factors may be even more salient determinants of oral health than what we previously supposed, perhaps interfering with the capacity to benefit from behavioral strategies that have been useful elsewhere. The improvement of children's oral health in high-risk populations characterized by poverty and multiple related life stresses may require more holistic approaches that address these formidable barriers.

Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party.

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.

Paediatric physeal sparing posterior cruciate ligament (PCL) reconstruction with parental donation allograft: Rationale and operative approach.

BACKGROUND: Paediatric PCL injuries are rare but constitute a significant management challenge. We describe a novel approach to the surgical management of an 11-year-old boy who presented with persisting symptomatic instability following 18months of failed conservative therapy. METHODS: PCL reconstruction was performed using a physeal sparing, all-inside technique under fluoroscopic control. This avoids the potential for iatrogenic growth injury. A parentally donated hamstrings allograft was used to ensure adequate graft size, and reinforced using a non-elastic two millimetre braided suture. Graft reinforcement safeguards against stretching during the early healing phase, but must be removed thereafter to avoid creating a physeal tether. RESULTS: At three months, clinical examination under anaesthesia showed equivalent PCL laxity in the operated knee compared to the normal contralateral knee. The graft reinforcement tape was incised as planned with no change in laxity assessment. Arthroscopic evaluation demonstrated a quiet joint with a well healed graft and no synovitis. Postoperative long leg radiographs showed no growth deformity against preoperative status. CONCLUSION: In paediatric patients with persisting symptomatic instability despite appropriate conservative management, surgical reconstruction of the PCL should be considered. Standard treatment has higher complication rates and poorer graft survival than in an adult cohort. Specific problems include iatrogenic growth plate injury causing growth arrest or angular deformity, inadequate graft size if using hamstrings autograft, and the additional technical challenge of small patient size. Early results from extra-physeal, all-inside PCL reconstruction using a parentally donated allograft are promising and may provide an alternative solution to traditional surgical management.

Serotonin transporter binding is reduced in seasonal affective disorder following light therapy.

OBJECTIVE: To investigate the effects of light therapy on serotonin transporter binding (5-HTT BPND ), an index of 5-HTT levels, in the anterior cingulate and prefrontal cortices (ACC and PFC) during winter in seasonal affective disorder (SAD). 5-HTT BPND fluctuates seasonally to a greater extent in SAD relative to health. We hypothesized that in SAD, 5-HTT BPND would be reduced in the ACC and PFC following light therapy. METHODS: Eleven SAD participants underwent [11 C] DASB positron emission tomography (PET) scans to measure 5-HTT BPND before and after 2 weeks of daily morning light therapy. RESULTS: The primary finding was a main effect of treatment on 5-HTT BPND in the ACC and PFC (repeated-measures manova, F(2,9) = 6.82, P = 0.016). This effect was significant in the ACC (F(1,10) = 15.11 and P = 0.003, magnitude of decrease, 11.94%) and PFC (F(1,10) = 8.33, P = 0.016, magnitude of decrease, 9.13%). 5-HTT BPND also decreased in other regions assayed following light therapy (repeated-measures manova, F(4,7) = 8.54, P = 0.028) including the hippocampus, ventral striatum, dorsal putamen, thalamus and midbrain (F(1,10) = 8.02-36.94, P < 0.0001-0.018; magnitude -8.83% to -16.74%). CONCLUSIONS: These results demonstrate that light therapy reaches an important therapeutic target in the treatment of SAD and provide a basis for improvement of this treatment via application of [11 C]DASB PET.

Light therapy and serotonin transporter binding in the anterior cingulate and prefrontal cortex.

OBJECTIVE: To investigate the effects of light therapy on serotonin transporter binding (5-HTT BPND ), an index of 5-HTT levels, in the anterior cingulate and prefrontal cortices (ACC and PFC) of healthy individuals during the fall and winter. Twenty-five per cent of healthy individuals experience seasonal mood changes that affect functioning. 5-HTT BPND has been found to be higher across multiple brain regions in the fall and winter relative to spring and summer, and elevated 5-HTT BPND may lead to extracellular serotonin loss and low mood. We hypothesized that, during the fall and winter, light therapy would reduce 5-HTT BPND in the ACC and PFC, which sample brain regions involved in mood regulation. METHOD: In a single-blind, placebo-controlled, counterbalanced, crossover design, [(11) C]DASB positron emission tomography was used measure 5-HTT BPND following light therapy and placebo conditions during fall and winter. RESULTS: In winter, light therapy significantly decreased 5-HTT BPND by 12% in the ACC relative to placebo (F1,9 = 18.04, P = 0.002). In the fall, no significant change in 5-HTT BPND was found in any region across conditions. CONCLUSION: These results identify, for the first time, a central biomarker associated with the intervention of light therapy in humans which may be applied to further develop this treatment for prevention of seasonal depression.

Bacteraemia incidence, causative organisms and resistance patterns, antibiotic strategies and outcomes in a single university hospital ICU: continuing improvement between 2000 and 2013.

OBJECTIVES: The optimal duration of antibiotic treatment in patients with bloodstream infections remains contentious, with concerns regarding both undertreatment and the encouragement of antibiotic resistance. In our ICU we traditionally use short-course antibiotic monotherapy as the mainstay of treatment. We sought to document the impact of this strategy on pathogen type, resistance patterns and patient outcomes. A comparison was made against data collected during a similar exercise in 2000. METHODS: We retrospectively reviewed data on all patients with community-, hospital- and ICU-acquired bacteraemia over a 6 month period (1 December 2012 to 31 May 2013) in a general medical-surgical ICU in a London university hospital. Causative pathogens, resistance patterns, use and duration of monotherapy or combination therapy, breakthrough and relapse rates, and patient outcomes were assessed. RESULTS: The 2013 cohort comprised 113 episodes in 87 patients. Short-course monotherapy (median course 4-5 days) was used in 65.7% of episodes (73.5% in 2000). As with the 2000 cohort, the incidence of antimicrobial resistance, fungaemia, bacteraemia breakthrough and relapse remained low. Of note, there was a decreasing incidence of ICU-acquired MRSA, MDR Gram-negative bacteraemia and fluconazole-resistant candidaemia. Hospital mortality was 32% (45% in 2000). CONCLUSIONS: Our strategy predominantly utilizing short-course antibiotic monotherapy remains effective in achieving good clinical outcomes among patients with bloodstream infections, with low rates of antibiotic resistance and clinical relapse. Prospective trials of short-course monotherapy are warranted to assess clinical efficacy and antimicrobial resistance.

Sucralfate paste enema: a new method of topical treatment for haemorrhagic radiation proctitis.

AIM: Rectal sucralfate has been reported to deliver clinical improvement in haemorrhagic radiation proctitis, but patients with active proctitis find the enema suspension difficult to retain thus reducing compliance and effectiveness. We describe a novel method of rectal administration via a low-volume sucralfate paste and report its results in a series of 23 patients. METHOD: Patients with rectal bleeding occurring more than 6 months after radiotherapy were shown how to prepare and self-administer sucralfate paste enemas (SPEs) twice daily for 6 weeks. The SPE was prepared using two sucralfate 1-g tablets mixed with 4.5 ml of water in an enema applicator producing a low-volume paste. The clinical response was evaluated by comparison of pre- and posttreatment clinical proctitis scores (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer). RESULTS: Eighteen male (postprostatic radiotherapy) and five female (postcervical radiotherapy) patients with a median age of 67 (32-75) years were included. The median interval between pelvic irradiation and SPE treatment was 24 (7-69) months. Twenty-two patients had full clinical scoring, of whom 16 (73%) demonstrated clinical improvement. Six (27%) had neither clinical improvement nor deterioration. Seven (32%) had resolution of all symptoms. CONCLUSION: Most patients demonstrated clinical improvement. This initial experience of the sucralfate paste enema may provide the basis for a prospective study of its effectiveness in the treatment of haemorrhagic radiation proctitis.

Osteotomy around the knee: evolution, principles and results.

PURPOSE: This article summarises the history and evolution of osteotomy around the knee, examining the changes in principles, operative technique and results over three distinct periods: Historical (pre 1940), Modern Early Years (1940-2000) and Modern Later Years (2000-Present). We aim to place the technique in historical context and to demonstrate its evolution into a validated procedure with beneficial outcomes whose use can be justified for specific indications. MATERIALS AND METHODS: A thorough literature review was performed to identify the important steps in the development of osteotomy around the knee. RESULTS: The indications and surgical technique for knee osteotomy have never been standardised, and historically, the results were unpredictable and at times poor. These factors, combined with the success of knee arthroplasty from the 1980s onward, led to knee osteotomy being regarded as an irrelevant surgical option by many surgeons. Despite its fluctuating reputation, this article demonstrates the reasons for the enduring practice of osteotomy, not least because achieving the appropriate alignment is now recognised as the foundation step when planning any surgical intervention. CONCLUSIONS: With appropriate patient selection, accurate pre-operative planning, modern surgical fixation techniques and rapid rehabilitation, osteotomy around the knee is now an effective biological treatment for degenerative disease, deformity, knee instability and also as an adjunct to other complex joint surface and meniscal cartilage surgery. LEVEL OF EVIDENCE: V.

The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light.

Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL.

Meta-analysis of the effects of dietary vitamin E supplementation on α-tocopherol concentration and lipid oxidation in pork.

Meta-analyses have been carried out to quantify the effect of dietary vitamin E on α-tocopherol accumulation and on lipid oxidation in porcine M. longissimus. Published results of 13 (vitamin E accumulation) and 10 (lipid oxidation) experiments respectively were used for the analyses. After a number of standardization procedures, a nonlinear relationship was found between the supplementary vitamin E and the accumulation of α-tocopherol in pork which approached a maximum value of 6.4 µg/g tissue. Pork lipid oxidation levels were described in terms of Thiobarbituric Acid Reacting Substances (TBARS) values. The statistical analysis revealed significant effect of vitamin E dose, muscle α-tocopherol concentration and supplementation time on TBARS, resulting in two prediction models for lipid oxidation. Meta-analysis has proven to be a valuable tool for combining results from previous studies to quantify the effects of dietary vitamin E. Further studies, carried out with standardized experimental protocols would be beneficial for model validation and to increase the predictive power of the derived models.

Trialling diagnosis-related groups classification in the Iranian health system: a case study examining the feasibility of introducing casemix.

This paper examines the quality of routinely collected information in an Iranian hospital in a trial of casemix classification. Australian Refined Diagnosis Related Groups (AR-DRG) were used to classify patient episodes. There were 327 DRGs identified, of which 20% had only 1 case. The grouper program identified invalid records for 4% of total separations. Approximately 4.5% of cases were classified into error DRGs and 3.4% were ungroupable. No complication and comorbidity effects were identified with 93% of total cases. R2 (variance in length of stay explained) was 44% for untrimmed cases, increasing to 63%, 57% and 58% after trimming by L3H3, IQR and 10th-95th percentile methods respectively.

Moving beyond health to flourishing: the effects of yoga teacher training.

Research in the medical and psychological fields has primarily followed a "disease-focused" approach to health. Although there is growing research on the components and outcomes of well-being, very few studies have focused on traditional practices that can be used as interventions to encourage human flourishing. The current study was developed to address this research gap. We suggest one effective method of increasing psychological well-being, the practice of yoga, an age-old practice that has been said to produce physical and psychological health. In this observational study, we examined associations with participation in a 4-week yoga teacher training resident program. Measurement instruments were chosen to capture changes in psychosocial health and human flourishing. Measurements were taken before the start of the program, immediately after the program, and 3 months postprogram. As expected, in this healthy population, the human flourishing scales showed more change than the psychosocial health scales. For example, in this healthy sample, there were no significant changes in perceived social support, quality of life, or self-efficacy from baseline to the 3-month follow-up. However, optimism, a positive psychology research measure, improved from baseline to follow-up. The mindfulness subscales of observation, awareness, and nonreactivity all improved following the training, suggesting that one benefit of yoga practice is a more refined ability to attend to one's inner experience. This study adds to the growing literature focusing on interventions that move beyond relieving pathology to those that produce optimal functioning and human thriving.

Antibiotic use and impact on outcome from bacteraemic critical illness: the BActeraemia Study in Intensive Care (BASIC).

BACKGROUND: The lack of prospective, randomized, controlled trial data to guide optimal antibiotic use in bacteraemic critically ill patients has led to a wide variety of strategies and major issues with drug resistance. We therefore prospectively investigated the epidemiology of bacteraemia and fungaemia in intensive care units (ICUs); and the impact of timing, type and appropriateness of antibiotic intervention. METHODS: We conducted a multinational, multicentre, prospective observational study in 132 ICUs from 26 countries with no interventions. RESULTS: 1702 patients [European (69.6%), Australasian (12.2%), South American (8.3%) and Asian (9.9%)] developed 1942 bacteraemic episodes over the study period. Mortality rates were similar for those receiving empirical (40.5%), semi-targeted (37.6%) or fully targeted (33.3%) antibiotic therapy (P=0.40), and in those initially receiving broad- (39.3%) or restricted-spectrum (39.1%) therapy (P=0.94). First-line therapy was effective in terms of the antibiogram (where available) in 70.4% of cases. This in vitro susceptibility ranged from 76.3% for broad-spectrum antibiotics to 46.3% for restricted-spectrum antibiotics (P<0.0001). However, no antibiotic policy-associated variable, including in vitro susceptibility (odds ratio 0.89, 95% confidence interval 0.61-1.30), was a statistically significant predictor of mortality. CONCLUSIONS: We could not show an impact of antibiotics on mortality in critically ill patients, despite in vitro activity and early commencement. Randomized, multicentre trials are urgently needed to establish the appropriate duration, timing and combinations of antibiotics that will both optimally treat infection and minimize development of resistance and other complications.

Casemix in the Islamic Republic of Iran: current knowledge and attitudes of health care staff.

Casemix is a tool that classifies patients according to their clinical similarity and the homogeneity of resources required. A descriptive study was conducted to assess the level of knowledge and attitude toward the casemix-based funding system among staff working in the Iranian Social Security Organization in Tehran. The survey showed that knowledge of casemix and diagnosis-related groups (DRG) was poor among the study group and any attempt to implement the casemix system--which about three-quarters of high-level staff had never heard of--would be likely to fail. This highlights the necessity for creating awareness of the casemix and DRG systems among the hospital staff before any action takes place.

Homeopathic combination remedy in the treatment of acute childhood diarrhea in Honduras.

BACKGROUND: Despite the widespread availability of oral rehydration therapy, diarrheal illness remains a major cause of morbidity and mortality around the world. Previous studies have shown individualized homeopathic therapy to be effective in treating childhood diarrhea, but this approach requires specialized training. OBJECTIVE: A homeopathic combination medicine, if effective, could be used by health personnel on a widespread basis. METHODS: A double-blind randomized controlled trial was conducted in Honduras to evaluate the effectiveness of a homeopathic combination therapy to treat acute diarrhea in children. A total of 292 children with acute diarrhea was recruited; 145 were randomized to the experimental group and 147 to the placebo group. Tablets containing a combined preparation of the five most common single homeopathic remedies used to treat diarrhea or placebo were administered by a parent after each unformed stool. Children were followed up daily for 7 days or until symptoms resolved, whichever occurred first. Time until resolution of symptoms, daily rate of unformed stools, and total number of unformed stools were compared between the two groups. RESULTS: There was no significant difference in the likelihood of resolution of diarrheal symptoms between the treatment and placebo groups (hazard ratio = 1.02, 95% confidence interval: 0.79-1.32), with a median time until resolution of 3 days for both groups. Children in the treatment group had an average of 2.6 unformed stools per day compared to 2.8 among those in the placebo group; this difference was not significant (p = 0.43). The median number of unformed stools was 7 among children in the treatment group and 8 among those in the placebo group (p = 0.41). DISCUSSION: The homeopathic combination therapy tested in this study did not significantly reduce the duration or severity of acute diarrhea in Honduran children. Further study is needed to develop affordable and effective methods of using homeopathy to reduce the global burden of childhood diarrhea.

Design, synthesis and biological activity of new CDK4-specific inhibitors, based on fascaplysin.

We present the design, synthesis, and biological activity of three classes of tryptamine derivatives, which are non-planar analogues of the toxic anti-cancer agent fascaplysin. We show these compounds to be selective inhibitors of CDK4 over CDK2, the most active compound has an IC50 for the inhibition of CDK4 of 6 microM.

Plasma glutamine concentrations in the horse following feeding and oral glutamine supplementation.

REASONS FOR PERFORMING STUDY: Pharmacological benefits of glutamine supplementation have been shown in athletically and clinically stressed human subjects. In the horse, infection and intense exercise have also been shown to significantly decrease plasma glutamine concentrations, but little is known on how best to supplement. OBJECTIVE: To evaluate whether ingestion of different foodstuffs, with or without L-glutamine (G) or a peptide (Pep) containing 31.5% w/w G in a water-stable form, could affect plasma glutamine concentrations (P-GC). MATERIALS AND METHODS: Nine feeds (molassed sugar beet-pulp (mSB); naked oats (nO); commercial mix (CM); mSB with 30 or 60 mg/kg bwt G or the G-molar equivalent of Pep; and CM with 60 mg/kg bwt G or equivalent Pep) were offered to 6 healthy mature horses on different days following overnight food restriction. The changes in P-GC were monitored for 8 h post feeding. RESULTS: After 1.5 h mean +/- s.d. AP-GC were -0.9 +/- 10.2% (mSB), +12.5 +/- 7.1% (nO) and +44.7 +/- 15.9% (CM; P<0.05). deltaP-GC with mSB supplemented with G was +60.9 +/- 30.0% (30 mg; P<0.05) and +156.8 +/- 34.6% (60 mg; P<0.05) at 1 h; deltaP-GC with Pep was 51.0 +/- 31.0% (30 mg equivalent, P<0.05) and +91.1 +/- 9.5% (60 mg equivalent, P<0.05) at 1 h. After 10 days of supplementation with 60 mg/kg bwt G, AP-GC following a further 60 mg/kg bwt G challenge showed a similar increase at 1 h of +154.3 +/- 37.9%; prevalues were unchanged. G and Pep added to CM, increased P-GC by 246.3 +/- 55.3 (+99.2%) and 252.3 +/- 94.2 micromol/l (96.7%) at 1.5 h with concentrations still above prevalues at 8 h (P<0.05). Apart from the CM (with or without supplement), pre P-GC was always regained by 4 h. Plasma NH3 and plasma protein concentrations were unaffected by supplementation with G or Pep. CONCLUSION: P-GC may be modified by appropriate supplementation with no apparent adverse effects. POTENTIAL RELEVANCE: Increasing P-GC through appropriate supplementation may be of benefit in the athletically or clinically stressed horse with lowered plasma glutamine concentrations.

Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle.

The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of Genotropin administered by the Genotropin ZipTip needle-free device and by conventional injection. Bioequivalence was established between the devices. In a separate open-label, randomized, multicenter, 2-period crossover study, pediatric patients underwent 2-weeks Genotropin treatment administered by the Genotropin ZipTip and by a fine-gauge needle device (>95% used the Genotropin Pen). In total, 128/133 patients who were treated completed the study. Genotropin ZipTip was well tolerated and >50% of patients found no difference between the devices for all parameters assessed. After study completion, >20% patients preferred to continue using Genotropin ZipTip. Although statistical analyses demonstrated superiority of the Genotropin Pen versus Genotropin ZipTip for bleeding, pain, soreness, and bruising, Genotropin ZipTip was considered to provide a safe and bioequivalent alternative to needle injection.