A Review of Propylene Glycol-free Melphalan Conditioning for Hematopoietic Cell Transplantation for Multiple Myeloma and Light Chain Amyloidosis.

Autologous hematopoietic cell transplantation (AHCT) remains a standard therapeutic option for patients with multiple myeloma (MM). Outcomes have improved for this patient group after first AHCT, with the use of novel agents in induction, as well as post-transplantation maintenance. High-dose melphalan remains the gold standard as the conditioning regimen for MM. Traditional melphalan is a lyophilized formulation that after reconstitution has insufficient chemical stability and water solubility, thus requiring the addition of propylene glycol to act as a cosolvent to improve these characteristics. After the reconstitution of melphalan with propylene glycol-containing solution, impurities can develop within 30 minutes, and if further dilution occurs, the potency of melphalan diminishes. Propylene glycol is associated with a spectrum of toxicities that can be dose limiting. Evomela is a propylene glycol-free melphalan (PGF-Mel) that at a high dose of 200 mg/2 (100 mg/m2/d for 2 days) is approved for conditioning before AHCT in MM patients. Once reconstituted by directly dissolving in saline solution, PGF-Mel solution can be stored in the vial for up to 1 hour at room temperature or for up to 24 hours at refrigerated temperature (2° to 8°C) with no significant degradation. The demonstrated stability, up to 24 hours at room temperature, results in reduced handling requirements and increased convenience and flexibility of administration. Since its approval, Evomela has been the subject of several retrospective and investigator-initiated studies. This review summarizes the prospective and real-world evidence on practical aspects of PGF-Mel and critically appraises the available data and its clinical implications.

A randomized controlled trial to evaluate propylene glycol alone or in combination with dextrose as a treatment for hyperketonemia in dairy cows.

Our objective was to investigate the effect of i.v. dextrose as an adjunct therapy to oral propylene glycol on the resolution of hyperketonemia (HYK; blood ß-hydroxybutyrate ≥1.2 mmol/L), disease incidence, and early lactation milk yield. Cows (n = 1,249) between 3 and 16 d in milk (DIM) from 4 New York dairy farms were screened once weekly for HYK for 2 wk. Those with HYK and no previous history of retained placenta, metritis, or HYK were randomly assigned to 1 of 3 treatment groups: 300 mL of oral 100% propylene glycol for 3 d (PG3); 300 mL of oral 100% propylene glycol for 3 d plus 500 mL i.v. 50% dextrose on d 1 (PG3D1); or 300 mL of oral 100% propylene glycol for 3 d plus 500 mL i.v. 50% dextrose on all 3 d (PG3D3). Cows with a blood ß-hydroxybutyrate <1.2 mmol/L at initial screening were re-screened the following week and randomly assigned to the above treatment groups if blood ß-hydroxybutyrate was ≥1.2 mmol/L. Cows were assessed for post-treatment HYK resolution 1 and 2 wk after initial HYK diagnosis. We collected farm-diagnosed occurrence of adverse events (sold, died, metritis, displaced abomasum, or ketosis) during the first 60 DIM and milk yield data from the first 10 wk of lactation from herd management software. We used mixed-effects multivariable Poisson regression models to assess the risk of post-treatment HYK resolution at 1 and 2 wk following initial HYK diagnosis and adverse event occurrence among treated cows. We used repeated-measures ANOVA to assess differences in average daily milk yield between treatments. The overall HYK incidence was 30.1% (n = 373). Sixty-four percent of cows (n = 237) were assigned to a treatment group in the first week (3 to 9 DIM), and 36% (n = 136) assigned the second week (10 to 16 DIM). The incidence of 1 or more adverse events during the first 60 DIM was 9.4% (n = 35). We found no effect of treatment on risk of post-treatment HYK resolution at wk 1 (PG3 56.9%, PG3D1 45.0%, PG3D3 50.0%) or wk 2 (PG3 60.0%, PG3D1 52.1%, PG3D3 59.5%) following initial diagnosis, or for risk of adverse event occurrence (PG3 7.4%, PG3D1 8.0%, PG3D3 12.6%). Average daily milk yield (mean ± SE) was similar between treatment groups (PG3: 42.7 ± 0.6 kg/d, PG3D1: 42.4 ± 0.6 kg/d, PG3D3: 42.6 ± 0.6 kg/d). The addition of dextrose for 1 or 3 d provided no improvement in resolution of ketosis assessed once weekly, reduction in adverse events during the first 60 d of lactation, or a difference in average daily milk yield during the first 10 wk of lactation.

Economic value of information from an alert system on physiological imbalance in fresh cows.

Physiological imbalance is an abnormal physiological condition that cannot be directly observed but is assumed to precede subclinical and clinical diseases in the beginning of lactation. Alert systems to detect the physiological imbalance in a cow using Fourier transform mid-infrared spectroscopy in milk have been developed. The objective of this study was to estimate the value of information provided from such system with different indicator accuracies, herd prevalence and prices. A decision tree was created to model the probabilities of detection and associated costs of test outcome, intervention and occurrence of disease. We assumed that the negative effect of physiological imbalance was the development of subclinical ketosis and that this negative effect was prevented by drenching the cows with propylene glycol for 5 days. We simulated the economic impact of subclinical ketosis mediated through physiological imbalance to be $194 per case. The results showed that if the alert system was highly accurate (Se = 0.99/Sp = 0.99), and the prevalence of physiological imbalance was 30 %, the value of information provided from the system is $19 per cow-year. In case the prevalence is 5 % or 50 %, the value of information is $3 and $13, respectively. These estimates for the value do not cover the capital costs and operational costs of the alert system. This study furthermore clearly demonstrated that in order to estimate the value of information correctly, it is important to consider that drenching all cows and not drenching any of the cows are the two relevant alternative options in the absence of the alert system. In conclusion, the decision tree and sensitivity analysis developed in this study show that final economic results are highly variable to the prevalence of physiological imbalance and highest at an intermediate prevalence. Other relevant factors are the costs associated with drenching and the cost associated with treating false positives and not treating false negatives. In addition, this study highlights the benefits of simulation to pinpoint where additional information is needed to further quantify the economic value and required accuracy of an indication-based intervention system.

Efecto antimicrobiano de la pasta 3-ATB y el hidróxido de calcio con distintos solventes / Antimicrobial effect of triple antibiotic paste and calcium hydroxide with different solvents

Objetivo: El objetivo de este estudio ha sido valorar cómo el hidróxido de calcio y la pasta triantibiótica (3-ATB) con agua destilada o propilenglicol actúan frente a una de las principales bacterias anaerobias facultativas presentes en dientes permanentes jóvenes con pulpa necrótica. Material y Método: Se llevó a cabo la siembra de la cepa bacteriana E.Coli (ATCC(R) 25922) en placas Petri para probar la susceptibilidad de los materiales mediante el método de difusión en agar. Se realizó la lectura de los resultados a las 48 horas mediante la medición de los halos de inhibición (mm) presentes en las placas. Resultados: La pasta tri-antibiótica mostró mayor inhibición que el hidróxido de calcio. Respecto a los solventes, la pasta 3-ATB ofreció mejor resultado combinada con propilenglicol, mientras que la respuesta del hidróxido de calcio fue más favorable al mezclar con agua destilada. Conclusiones: La pasta 3-ATB es más efectiva contra microorganismos anaerobios facultativos que el hidróxido de calcio, independientemente del solvente utilizado. En cuanto al solvente, el propilenglicol es más efectivo con pasta tri-antibiótica y el hidróxido de calcio lo es con agua destilada

Objective: The objective of this study was to assess how calcium hydroxide and triple antibiotic paste (3-ATB) with distilled water or propylene glycol act against one of the main facultative anaerobic bacteria present in young permanent teeth with necoritc pulp. Material and Methods: The seeding of the E.Coli (ATCC(R) 25922) was carried out in Petri dishes to test the susceptibility of the materials by the agar diffusion method. The results were read at 48 hours by measuring the inhibition zones (mm) present in the plates. Results: 3-ATB paste showed greater inhibition than calcium hydroxide. Regarding the solvents, 3-ATB paste offered better re-sults with propylene glycol, while the calcium hydroxide response was more favorable mixed with distilled water. Conclusions: 3-ATB paste is more effective against facultative anaerobic microorganisms than calcium hydroxide, regardless of the solvent used. As for the solvent, propylene glycol is more effective with 3-ATB paste while calcium hydroxide with distilled water

Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism.

Acute pulmonary embolism may cause right heart failure due to increased pulmonary vascular resistance and arterial hypoxemia. Effective vasodilator therapy of the pulmonary hypertension is highly needed. Therefore, we investigated the effects of a newly developed effective pulmonary vasodilator, the organic mononitrites of 1,2-propanediol (PDNO), in a rabbit model of acute pulmonary embolism. In anesthetized and ventilated rabbits, systemic and pulmonary hemodynamics, exhaled nitric oxide (NO), plasma nitrite concentration, and blood gases were monitored. First, dose-response experiments with intravenous and left heart ventricle infusions of PDNO and inorganic nitrite were done in naive animals and in pulmonary hypertension induced by a thromboxane A2 analogue. Second, acute pulmonary embolism was induced and either PDNO or placebo were administered intravenously within 20 minutes and evaluated within 1 hour after pulmonary embolization. PDNO intravenously, in contrast to inorganic nitrite intravenously, increased exhaled NO and counteracted pulmonary hypertension and vasodilated the systemic circulation, dose-dependently, thereby showing efficient NO donation. Pulmonary embolization induced pulmonary hypertension and gas exchange disturbances. PDNO significantly decreased and normalized pulmonary vascular resistance and the right ventricle rate-pressure product, without causing tolerance, with no significant side effects on the systemic circulation, nor on blood-gas values or on methemoglobin formation. In conclusion, PDNO is a NO donor and an efficient vasodilator in the pulmonary circulation. Treatment with this or similar organic nitrites intravenously may be a future option to avoid right heart failure in life-threatening acute pulmonary embolism.

Effect of two treatment protocols for ketosis on the resolution, postpartum health, milk yield, and reproductive outcomes of dairy cows.

We determined the effect of ketosis treatment with propylene glycol (PG) or PG plus l-carnitine and methionine (Metabolase®, Fatro, Bologna, Italy) on the resolution, postpartum health, milk yield, and reproductive performances of dairy cows. Blood from 475 Holstein cows was collected weekly until 4 weeks after calving to measure blood ß-hydroxybutyrate (BHBA) concentrations. Cows with blood BHBA concentration ≥1.2 mmol/L were diagnosed with ketosis and were enrolled. One hundred and fifty cows diagnosed with ketosis were randomly assigned to three treatment groups (Day 0): (1) PG (300 g, PO) for 3 days (PG group, n = 50), (2) PG (300 g, PO) plus l-carnitine (1.25 g) plus methionine (5 g, IV) for 3 days (PG + CM group, n = 50), and (3) no treatment (control group, n = 50). On Day 3, blood was collected to evaluate whether the ketosis had resolved. Cows in the PG and PG + CM groups with blood BHBA ≥1.2 mmol/L were retreated for an additional 2 days, and then blood BHBA concentration was evaluated on Days 5 and 10. Blood glucose and haptoglobin concentrations, rumen fill score (RFS), and body condition score (BCS) were measured on Days 0, 3, 5, and 10. Postpartum complications, milk yield during the first 2 months, and reproductive outcomes were evaluated. The probability of resolution from ketosis was higher (P < 0.05) in the PG + CM group than in the control group on Days 3, 5, and 10 (odds ratio: 2.6-6.3). Blood BHBA in the PG + CM group was lower (P < 0.05) than that of the control group on Days 3 and 5, whereas blood glucose in the PG + CM group was higher (P < 0.05) than that of the control group on Days 3 and 5. RFS in the PG and PG + CM groups was higher than that of the control group on Day 10 (P < 0.01), while BCS loss from Day 0-10 in the control group was higher than those of the PG and PG + CM groups (P < 0.05). Milk yields on the 30th and 60th days postpartum were higher in the PG + CM group than the control and PG groups (P < 0.05). Postpartum complications and intervals between calving and first postpartum insemination or pregnancy did not differ among the groups (P > 0.05). In conclusion, treatment of dairy cows with PG plus l-carnitine and methionine improved the chances of resolution of ketosis and increased milk yield, while affecting neither the incidence of postpartum complications nor reproductive performance.

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Safety and efficacy of a hydroxypropyl guar/polyethylene glycol/propylene glycol-based lubricant eye-drop in patients with dry eye.

AIMS: To demonstrate non-inferiority of a hydroxypropyl guar/polyethylene glycol/propylene glycol lubricating eye-drop (HPG/PEG/PG) compared with an osmoprotective carboxymethylcellulose/glycerine eye-drop (O/CMC) for ocular surface staining. METHODS: This was a multicentre, randomised, observer-masked, parallel-group study. Adults with dry eye instilled HPG/PEG/PG/ or O/CMC 4 times daily for 35 days and then as needed through day 90. Total ocular surface staining (TOSS) score changes from baseline and Impact of Dry Eye on Everyday Life (IDEEL) treatment satisfaction module scores were assessed. Non-inferiority, based on TOSS score change from baseline, was concluded if the upper limit of the 2-sided CI was <2 units. RESULTS: Mean±SD patient age was 64.4±13.7 years; 94 patients were randomised to treatment (HPG/PEG/PG, n=46; O/CMC, n=48). Mean±SE TOSS score change from baseline to day 35 was -2.2±0.33 with HPG/PEG/PG and -1.7±0.47 with O/CMC (treatment difference, -0.47±0.47; p=0.38), and the non-inferiority criterion was met. IDEEL treatment satisfaction scores were similar between groups at day 35 and day 90. The most frequently reported adverse event was eye irritation (HPG/PEG/PG, n=2; O/CMC, n=3). CONCLUSIONS: HPG/PEG/PG and O/CMC reduced ocular surface damage, and HPG/PEG/PG was non-inferior to O/CMC. Both treatments were effective, convenient and well tolerated. TRIAL REGISTRATION NUMBER: NCT01863368, Results.

Economic value of ionophores and propylene glycol to prevent disease and treat ketosis in Canada.

A partial budget model was developed to evaluate the economic value of Rumensin Controlled Release Capsule (CRC) boluses when administered before calving to reduce disease and increase milk production. After accounting for disease incidences in a herd and the percentage by which Rumensin CRC can reduce them, and the increase in milk production attributable to administration of Rumensin CRC, the return on investment (ROI) per lactation was 4:1. Another partial budget model was developed to estimate the economic value of propylene glycol (PG) to treat ketosis when diagnosed by 3 different cow-side tests or when administered to all cows without using any cow-side testing. After accounting for the sensitivity and specificity of each test, ROI per lactation ranged from 2:1 to 4:1. The ROI was 2:1 when no cow-side testing was used. In conclusion, prevention of diseases that occur in the postpartum period and treatment of ketosis after calving yielded a positive ROI that varies based on disease incidence and method of diagnosis.

Valeur économique des ionophores et du propylèneglycol pour prévenir la maladie et traiter l'acétonémie au Canada. Un modèle de budget partiel a été développé pour évaluer la valeur économique des bolus de capsules à libération contrôlée (CLC) de Rumensin lors de l'administration avant le vêlage afin de réduire les maladies et d'accroître la production de lait. Après avoir tenu compte de l'incidence des maladies dans un troupeau et du pourcentage par lequel la CLC de Rumensin peut les réduire et de l'augmentation de la production de lait attribuable à l'administration de la CLC de Rumensin, le rendement du capital investi (RCI) par lactation était de 4:1. Un autre modèle de budget partiel a été développé pour estimer la valeur économique du propylèneglycol (PG) afin de traiter l'acétonémie lors du diagnostic par 3 tests différents pour les vaches ou lors de l'administration à toutes les vaches sans le recours à des tests auprès des vaches. Après avoir tenu compte de la sensibilité et de la spécificité de chaque test, le RCI par lactation s'échelonnait de 2:1 à 4:1. Le RCI était de 2:1 lorsqu'aucun test auprès des vaches n'était utilisé. En conclusion, la prévention des maladies qui se produit dans la période postpartum et le traitement de l'acétonémie après le vêlage a donné un RCI positif qui varie selon l'incidence de maladies et la méthode de diagnostic.(Traduit par Isabelle Vallières).

Método alternativo para inserção da pasta de hidróxido de cálcio no sistema de canais radiculares como medicação intracanal / Alternative method for placing calcium hydroxide paste into the root canal system as intracanal medication

Introdução: o objetivo do presente trabalho é apresentar um método alternativo para inserção da pasta de hidróxido de cálcio na medicação intracanal, após o preparo químico-mecânico do sistema de canais radiculares. Métodos: a técnica consistiu no uso de seringas de plástico descartáveis de 1,2 mL (Ultradent) e pontas para irrigação/ aspiração (Capillary Tips - Ultradent). Para controle da profundidade do material a ser inserido, utilizou-se um stop de silicone na ponta da Capillary Tips, no comprimento de trabalho do canal radicular, previamente instrumentado. Em seguida, a lubrificação da seringa plástica e da ponta foi realizada com propilenoglicol. A manipulação do hidróxido de cálcio PA com propilenoglicol foi realizada utilizando-se uma espátula #24 sobre uma placa de vidro, até obter uma pasta de consistência fluída e homogênea. Para inserção da pasta de Ca(OH)2 dentro da seringa, utilizou-se a espátula de manipulação. Imediatamente após, a medicação intracanal pôde ser levada aos canais radiculares. Conclusão: a técnica de inserção de hidróxido de cálcio nos sistemas radiculares proposta apresentou resultados satisfatórios, previsibilidade clínica e facilidade na preparação.

Evaluation of a fibrate, specific stimulant of PPARα, as a therapeutic alternative to the treatment of clinical ovine pregnancy toxaemia.

Ovine pregnancy toxaemia is a metabolic disorder affecting sheep in their last 6 weeks of pregnancy as a result of their inability to maintain adequate energy homoeostasis. Different alternative treatments are available with variable results. The aim of this research was to evaluate a peroxisome proliferator-activated receptor alpha (PPARα) stimulant as an alternative to treat clinical pregnancy toxaemia. Thirty-three adult sheep, with known gestation date and carrying a single foetus, were fasted from day 130 of gestation until animals showed clinical disease. From that moment onwards, sheep were treated during 6 days with three different therapeutic alternatives: 10 mg/kg of 2-methyl-2-phenoxy-propionic acid; 10 mg/kg of 2-methyl-2-phenoxy-propionic acid + 100 mL of propylene glycol oral; or 100 mL of propylene glycol oral. Glycaemia and serum ß-hydroxybutyrate (BHOB) were determined daily. Liver biopsies were taken at day 130 of gestation, at the beginning and end of treatments and at 5 days postpartum, evaluating the extent and degree of the steatosis lesion. Even though in sheep treated with 2-methyl-2-phenoxy-propionic acid, serum concentrations of glucose and BHOB recovered more slowly, we conclude that 2-methyl-2-phenoxy-propionic acid alone or combined with propylene glycol can be used as an alternative to effectively treat fatty liver, and therefore pregnancy toxaemia.

Clinical Effectiveness of Moisturizers in Atopic Dermatitis and Related Disorders: A Systematic Review.

BACKGROUND: Moisturizers are widely used for atopic dermatitis (AD) and related conditions, but available evidence of their effectiveness has not been reviewed in a systematic fashion. OBJECTIVES: Our objective was to investigate the effectiveness of emollients, as a group and individually, in the treatment of AD and related conditions, by means of a systematic review. DATA SOURCES: Studies indexed in MEDLINE and/or Embase before 16 January 2015. STUDY ELIGIBILITY CRITERIA: Controlled clinical studies comparing the clinical effect of a moisturizer against its vehicle, another moisturizer, or no treatment were eligible. For the outcomes transepidermal water loss (TEWL) and stratum corneum hydration, uncontrolled before-after designs were also eligible. PARTICIPANTS: Participants were patients with AD, irritant hand dermatitis, and/or ichthyosis vulgaris. RESULTS: Out of the 595 publications initially identified, 45 (48 studies, 3262 patients) were eligible for inclusion. A vast majority of studies indicate that moisturizers have beneficial effects on clinical symptoms [SCORAD (SCORing Atopic Dermatitis) reductions ranging from 0 to 2.7 points], TEWL (range 0 to -12.2 g/m(2)h) and stratum corneum hydration (range +8 to +100%). Direct comparisons between individual moisturizers are still scarce, but the clinical effect appears to be much more well-documented for urea and glycerin than, for example, propylene glycol, lactate, ceramide, and aluminum chlorohydrate. Compared with urea studies, glycerin studies were more often associated with a high risk of bias. LIMITATIONS: Due to differences in study designs and outcome measures, a quantitative meta-analytic approach was not deemed feasible, and formal indicators of publication bias such as funnel plots could not be used. However, a large number of moderately sized studies with positive outcomes could be compatible with selective publishing of favourable results. CONCLUSIONS: The clinical effect of moisturizers is well-documented. Urea-based preparations may be preferable as a first-line treatment, but there is an unmet need for well-powered comparisons between individual moisturizers.

Utility of inline milk fat and protein ratio to diagnose subclinical ketosis and to assign propylene glycol treatment in lactating dairy cows.

The objective was to identify a fat-to-protein ratio (FPR) cut-off to diagnose subclinical ketosis (SCK) and to evaluate the effect of propylene glycol (PPG) treatment of cows with high FPR. The optimized cut-off was > 1.42; sensitivity (Se) = 92%; specificity (Sp) = 65%. A cut-off > 1.5 was selected for the PPG trial for balanced Se-Sp. Fat-to-protein ratio cut-offs > 1.25, 1.35, 1.50, 1.60, and 1.70 resulted in Se-Sp of 100% to 49%, 96% to 59%, 75% to 78%, 33% to 90%, and 8% to 96%, respectively. The proportions of cows with FPR > 1.25, 1.35, 1.42, 1.50, 1.60, and 1.70 were 60%, 50%, 44%, 30%, 14%, and 6%, respectively. Incidences of clinical ketosis and milk yield were similar between cows that received 400 mL of PPG (n = 34) and control cows (n = 38). Prevalence of SCK at enrollment was 29.2%; therefore, FPR > 1.5 is not indicated for treatment. Lower cut-offs should be used for screening.

Utilité du ratio de matière grasse et de protéine sur la ligne de traite pour diagnostiquer une cétose subclinique et assigner le traitement au propylèneglycol chez les vaches laitières en lactation. L'objectif consistait à identifier un seuil du ratio de matière grasse et de protéine (RMGP) pour diagnostiquer une cétose subclinique et évaluer l'effet du traitement au propylèneglycol (PPG) chez les vaches présentant un RMGP élevé. Le seuil optimisé était de > 1,42; la sensibilité (Se) = 92 %; la spécificité (Sp) = 65 %. Un seuil de > 1,5 a été choisi pour l'essai au PPG pour des Se-Sp équilibrées. Des seuils de ratios de matière grasse et protéine de > 1,25, 1,35, 1,50, 1,60 et 1,70 ont produit des Se-Sp de 100 % et 49 %, de 96 % et 59 %, 75 % et 78 %, de 33 % et 90 % et de 8 % et 96 %, respectivement. Les proportions des vaches avec un RMGP de > 1,25, 1,35, 1,42, 1,50, 1,60 et 1,70 étaient de 60 %, 50 %, 44 %, 30 %, 14 % et 6 %, respectivement. L'incidence de cétose clinique et la production de lait étaient semblables entre les vaches qui avaient reçu 400 mL de PPG (n = 34) et les vaches témoins (n = 38). La prévalence de cétose subclinique au recrutement était de 29,2 %; par conséquent, un RMGP de > 1,5 n'est pas indiqué pour le traitement. Des seuils inférieurs devraient être utilisés pour le dépistage.(Traduit par Isabelle Vallières).

The effect of using propylene glycol as a vehicle on the microhardness of mineral trioxide aggregate.

While it has been proven that the handling properties of mineral trioxide aggregate (MTA) are improved upon mixing it with propylene glycol (PG), this study sought to evaluate how PG affects the microhardness of MTA in terms of setting quality. MTA was mixed with different proportions of distilled water (DW) and PG to prepare 5 groups (n = 30). The DW/PG percent proportions used in Groups 1-5 were 100/0, 80/20, 50/50, 20/80, and 0/100, respectively. The mixed MTA was condensed into acrylic molds. Half of the samples of each group were evaluated on Day 4, the other half on Day 28. The results indicated that PG reduces the microhardness of MTA, thus adversely affecting its setting process. Group 2 (80% DW/20% PG) best improved the handling of MTA without a significant reduction in setting quality.

Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis.

This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. ß-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle.

Searching for Medical Substances Safe for Mother and Child, Facilitating the Delivery of Pain Management and Decreasing Exhaustion--Evaluation of Obstetric Gel by Pregnant Women.

The aim of the present study was to determine whether applying obstetric gel, a noninvasive method of pain management that is safe both for the mother and the child, during labor influences delivery satisfaction by facilitating pain management and decreasing exhaustion. Forty-seven primiparous women were included in the study: 23 on whom during the delivery gel was used and 24 whose delivery proceeded without the use of a gel (control group). The following research tools were used for the evaluation of satisfaction with the course of the delivery: Visual Analogue Scale (VAS), self-authorship survey, and the State-Trait Anxiety Inventory. There were no significant differences in intensification of pain in the first and second periods of delivery, exhaustion after delivery and intensification of pain in the second period of delivery, and increased anxiety between the study group and the control group. Our results suggest that application of obstetric gel during the first and second period of delivery does not significantly influence women's satisfaction with the course of delivery.

Moisturizing treatment of patients with atopic dermatitis and ichthyosis vulgaris improves dry skin, but has a modest effect on gene expression regardless of FLG genotype.

BACKGROUND: Loss-of-function mutations in FLG (encoding filaggrin) are a predisposing factor for atopic dermatitis (AD) and cause ichthyosis vulgaris (IV). Patients with AD and IV display impaired skin barrier and dry skin, and altered epidermal expression of genes in pro-inflammatory and lipid metabolic pathways are often evident. OBJECTIVES: To evaluate the effect of three different moisturizers on skin barrier function and epidermal gene expression in patients with AD/IV in relation to FLG mutation status. METHODS: Patients (n = 43) were classified according to their FLG status: AD with FLG+/+ (n = 14), AD with FLG+/- (n = 14), and AD/IV with FLG-/- (n = 15). Dryness score and transepidermal water loss (TEWL) were monitored on volar forearms, and punch biopsies were taken for analysis of gene expression. Measurements were repeated after 4 weeks of treatment with either of two moisturizers on each forearm. RESULTS: Treatment with any of the three moisturizers significantly reduced dryness score and TEWL in the group as a whole. FLG-/- patients displayed the largest reduction in dryness score. Only minute changes occurred in the mRNA expression of 15 selected epidermal genes. CONCLUSIONS: Moisturizing treatment improves dry skin and certain aspects of abnormal skin barrier function, especially in patients with AD/IV and dual FLG mutations, but does not normalize the epidermal gene expression profile.

An economic analysis of hyperketonemia testing and propylene glycol treatment strategies in early lactation dairy cattle.

The purpose was to develop stochastic economic models which address variation in disease risks and costs in order to evaluate different simulated on-farm testing and propylene glycol (PG) treatment strategies based on herd hyperketonemia (HYK) incidence during the first 30 DIM. Data used in model development concerning the difference in health and production consequences between HYK and non-ketotic cows were based on results from 10 studies representing over 13,000 cows from 833 dairy farms in North America, Canada, and Europe. Inputs for PG associated variables were based on a large field trial using cows from 4 free-stall dairy herds (2 in New York and 2 in Wisconsin). Four simulated on-farm testing and treatment strategies were analyzed at herd HYK incidences ranging from 5% to 80% and included: 1) treating all cows with 5d of PG starting at 5 DIM, 2) testing all cows for HYK 1 day per week (e.g. Mondays) from 3 to 16 DIM and treating all positive cows with 5d of oral PG, 3) testing all cows for HYK 2 days per week (e.g. Mondays and Thursdays) from 3 to 9 DIM and treating all positive cows with 5d of oral PG, and 4) testing all cows for HYK 3 days per week (e.g. Mondays, Wednesdays, and Fridays) from 3 to 16 DIM and treating all positive cows with 5d of oral PG. Cost-benefit analysis included the costs associated with labor to test cows, ß-hydroxybutyrate test strips, labor to treat cows, PG, and the associated gain in milk production, decrease in DA and early removal risks of PG treated HYK positive cows compared to non-treated HYK positive cows. Stochastic models were developed to account for variability in the distribution of input variables. Per 100 fresh cows in a herd with an HYK incidence of 40%, the mean economic benefits of the 4 different strategies were $1088, $744, $1166, and $760, respectively. Testing cows 2 days per week from 3 to 9 DIM was the most cost-effective strategy for herds with HYK incidences between 15% and 50%; above 50%, treating all fresh cows with 5d of PG was the most cost-effective strategy. These results show that for herds similar to those used in model, when herd HYK incidences rise above 25%, almost any HYK testing and treatment protocol will be economically beneficial for the farm.

Ketosis treatment in lactating dairy cattle.

This article provides an update on ketosis treatment regimens. The ketosis treatment literature is reviewed and the findings are summarized. Current treatment recommendations and areas for future research are provided.

Ultrasonography as a diagnostic and prognostic approach in cattle and buffaloes with fatty infiltration of the liver.

The aim of the present study was to determine whether ultrasonographic evaluation of the hepatic parenchyma could be used as a diagnostic and prognostic approach in cows and buffaloes with hepatic lipidosis. For this purpose, cows (n=16) and buffaloes (n=10) with fatty infiltration of the liver were examined by ultrasonography. Treated cows and buffaloes were monitored for hepatic changes ultrasonographically, biochemically and histologically. Clinical findings were non-specific and included anorexia, recumbency, muzzle necrosis, and icteric mucosal membranes. Laboratory data revealed neutrophilia, hyper gamma-globulinemia, elevated activities of aspartate aminotransferase, gamma-glutamyl transpeptidase, creatine kinase and lactate dehydrogenase, and high concentrations of insulin, total bilirubin, non-esterified fatty acids and beta-hydroxyl butyric acid. Laboratory results 7, and 21 days after treatment showed progressive improvement in the chemistry profile. On admission, ultrasonographic examination of the hepatic parenchyma in cows and buffaloes revealed either increased or decreased hepatic echogenicity; histologic examination revealed marked fatty infiltration of the hepatocytes. One week after treatment, the hepatic parenchyma was visualized easily, liver boundaries were clearly imaged, and histologic examination of hepatic specimen showed a moderate degree of fatty infiltration. Three weeks after treatment, the hepatic parenchyma was almost similar to normal, the hepatic and portal blood vessels could be easily imaged, and the histologic picture had greatly improved where the liver resembled the normal organ. Six cows and seven buffaloes made a full recovery while the remaining ten cows and three buffaloes were slaughtered and thoroughly examined postmortem. Ultrasonography showed a good correlation with histologic and laboratory findings.